Publications by authors named "Joshua Boateng"

65 Publications

Medicated multi-targeted alginate-based dressings for potential treatment of mixed bacterial-fungal infections in diabetic foot ulcers.

Int J Pharm 2021 Sep 19;606:120903. Epub 2021 Jul 19.

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Central Ave., Chatham Maritime, Kent ME4 4TB, UK. Electronic address:

Recently developed medicated dressings target either bacterial or fungal infection only, which is not effective for the treatment of mixed infections common in diabetic foot ulcers (DFUs). This study aimed to develop advanced bioactive alginate-based dressings (films and wafers) to deliver therapeutically relevant doses of ciprofloxacin (CIP) and fluconazole (FLU) to target mixed bacterial and fungal infections in DFUs. The alginate compatibility with the drugs was confirmed by SEM, XRD, FTIR and texture analysis, while the medicated wafers showed better fluid handling properties than the films in the presence of simulated wound fluid. The dressings showed initial fast release of FLU followed by sustained release of CIP which completely eradicated E. coli, S. aureus, P. aeruginosa and reduced fungal load (C. albicans) by 10-fold within 24 h. Moreover, the medicated dressings were biocompatible (>70% cell viability over 72 h) with human primary adult keratinocytes and in-vitro scratch assay showed 65-68% wound closure within 7 days.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120903DOI Listing
September 2021

Wound dressings as growth factor delivery platforms for chronic wound healing.

Expert Opin Drug Deliv 2021 06 3;18(6):737-759. Epub 2021 Jan 3.

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Central Avenue, Chatham Maritime, Kent, UK.

: Years of tissue engineering research have clearly demonstrated the potential of integrating growth factors (GFs) into scaffolds for tissue regeneration, a concept that has recently been applied to wound dressings. The old concept of wound dressings that only take a passive role in wound healing has now been overtaken, and advanced dressings which can take an active part in wound healing, are of current research interest.: In this review we will focus on the recent strategies for the delivery of GFs to wound sites with an emphasis on the different approaches used to achieve fine tuning of spatial and temporal concentrations to achieve therapeutic efficacy.: The use of GFs to accelerate wound healing and reduce scar formation is now considered a feasible therapeutic approach in patients with a high risk of infections and complications. The integration of micro - and nanotechnologies into wound dressings could be the key to overcome the inherent instability of GFs and offer adequate control over the release rate. Many investigations have led to encouraging outcomes in various and wound models, and it is expected that some of these technologies will satisfy clinical needs and will enter commercialization.
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http://dx.doi.org/10.1080/17425247.2021.1867096DOI Listing
June 2021

Efficacy and Metabolism of the Antimalarial Cycleanine and Improved Antiplasmodial Activity of Semisynthetic Analogues.

Antimicrob Agents Chemother 2021 01 20;65(2). Epub 2021 Jan 20.

School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, United Kingdom

Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 2'-norcocsuline [compound 3]) isolated from the Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semisynthetic analogues (compounds 4 and 5) of cycleanine. The antiproliferative effects against a chloroquine-resistant strain were determined using a SYBR green 1 fluorescence assay. The antimalarial activity of cycleanine is then investigated in suppressive, prophylactic, and curative murine malaria models after infection with a chloroquine-sensitive strain. BBIQ alkaloids (compounds 1 to 5) exerted antiplasmodial activities with 50% inhibitory concentration (IC) at low micromolar concentrations and the two semisynthetic cycleanine analogues showed an improved potency and selectivity compared to those of cycleanine. At oral doses of 25 and 50 mg/kg body weight of infected mice, cycleanine suppressed the levels of parasitemia and increased mean survival times significantly compared to those of the control groups. The metabolites and metabolic pathways of cycleanine were also studied using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastric administration of cycleanine. The metabolic pathways of cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these and results provide a basis for the future evaluation of cycleanine and its analogues as leads for further development.
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http://dx.doi.org/10.1128/AAC.01995-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848973PMC
January 2021

Physicochemical characteristics and permeation of loratadine solid lipid nanoparticles for transdermal delivery.

Ther Deliv 2020 11 23;11(11):685-700. Epub 2020 Nov 23.

Bavarian Polymer Institute, KeyLab 'Electron & Optical Microscopy', University of Bayreuth, Bayreuth, Germany.

To prepare loratadine-loaded solid lipid nanoparticles (SLNs) using a modified two-step ultrasound-assisted phase inversion temperature (PIT) process. Loratadine was dissolved in beeswax and Tween 80 was dissolved in water. The two phases were mixed together to prepare a water-in-oil emulsion preconcentrate (w/o) at a PIT of 85°C, followed by gradual water addition at 25°C to trigger nanoparticles formation (o/w). Kinetic stability was investigated. No change in the size was observed within 6 months. Fourier-transform infrared spectroscopy demonstrated stability of the emulsions via molecular structure of water at the interface of the o/w nanoemulsions. SLNs enhanced the skin permeation of loratadine. Stable SLNs were successfully prepared by ultrasound-assisted PIT.
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http://dx.doi.org/10.4155/tde-2020-0075DOI Listing
November 2020

In vitro, ex vivo and in vivo evaluation of taste masked low dose acetylsalicylic acid loaded composite wafers as platforms for buccal administration in geriatric patients with dysphagia.

Int J Pharm 2020 Nov 1;589:119807. Epub 2020 Sep 1.

School of Science, Faculty of Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK. Electronic address:

This study reports the development and characterization of taste masked, freeze-dried composite wafers for potential oral and buccal delivery of low dose aspirin (acetylsalicylic acid) to prevent thrombosis in elderly patients with dysphagia. The wafers were formulated by combining metolose (MET) with carrageenan (CAR), MET with chitosan (CS) at low molecular weight or CAR with CS using 45% v/v ethanol as solvent for complete solubilization of acetylsalicylic acid. Each wafer contained 75 mg of acetylsalicylic acid and sweetener (sucralose, stevia or aspartame) with a drug: sweetener ratio of 1:1 w/w. The formulations were characterized for physical properties using texture analyzer (hardness and mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy, swelling capacity, and in vitro drug dissolution. Further, permeation studies with three different models (Permeapad™ artificial barrier, EpiOral™ and porcine buccal mucosa) using HPLC, cell viability using MTT assay and in vivo taste masking evaluation using human volunteers were undertaken. The sweeteners increased the hardness and adhesion of the wafers, XRD showed the crystalline nature of the samples which was attributed to acetylsalicylic acid, SEM confirmed a compacted polymer matrix due to recrystallized acetylsalicylic acid and sweeteners dispersed over the surface. Drug dissolution studies showed that acetylsalicylic acid was rapidly released in the first 20 min and then continuously over 1 h. EpiOral™ had a higher cumulative permeation than porcine buccal tissue and Permeapad™ artificial barrier, while MTT assay using Vero cells (ATCC® CCL-81) showed that the acetylsalicylic acid loaded formulations were non-toxic. In vivo taste masking study showed the ability of sucralose and aspartame to mask the bitter taste of acetylsalicylic acid and confirm that acetylsalicylic acid loaded MET:CAR, CAR:CS and MET:CS composite wafers containing sucralose or aspartame have potential for buccal delivery of acetylsalicylic acid in geriatric patients with dysphagia.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119807DOI Listing
November 2020

Bioprinting and Preliminary Testing of Highly Reproducible Novel Bioink for Potential Skin Regeneration.

Pharmaceutics 2020 Jun 13;12(6). Epub 2020 Jun 13.

School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent ME4 4TB, UK.

Three-dimensional (3D) bioprinting is considered as a novel approach in biofabricating cell-laden constructs that could potentially be used to promote skin regeneration following injury. In this study, a novel crosslinked chitosan (CH)-genipin (GE) bioink laden with keratinocyte and human dermal fibroblast cells was developed and printed successfully using an extruder-based bioprinter. By altering the composition and degree of CH-GE crosslinking, bioink printability was further assessed and compared with a commercial bioink. Rheological analysis showed that the viscosity of the optimised bioink was in a suitable range that facilitated reproducible and reliable printing by applying low pressures ranging from 20-40 kPa. The application of low printing pressures proved vital for viability of cells loaded within the bioinks. Further characterisation using MTT assay showed that cells were still viable within the printed construct at 93% despite the crosslinking, processing and after subjecting to physiological conditions for seven days. The morphological study of the printed cells showed that they were mobile within the bioink. Furthermore, the multi-layered 3D printed constructs demonstrated excellent self-supportive structures in a consistent manner.
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http://dx.doi.org/10.3390/pharmaceutics12060550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356948PMC
June 2020

Surface Modification of Mobile Composition of Matter (MCM)-41 Type Silica Nanoparticles for Potential Oral Mucosa Vaccine Delivery.

J Pharm Sci 2020 07 30;109(7):2271-2283. Epub 2020 Mar 30.

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent, ME4 4TB, UK. Electronic address:

Development of mobile composition of matter (MCM)-41 silica nanoparticles faces challenges, e.g. surface charge properties, antigen loading efficiency, protecting from enzymes and harsh GIT environment and effective release at target mucosal site. We report the production and characterization of polymer and amine modified MCM-41 type silica nanoparticles for oral antigen delivery using ovalbumin (OVA) as model antigen. Nanoparticles were characterized by dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, circular dichroism (CD), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), mucin binding, stability in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and in vitro OVA release in SGF and SIF. Unmodified nanoparticles size of 146 nm increased to 175-321 nm after modification while modified particles remained intact for more than 3 h in SGF and 96 h in SIF (DLS and SEM). Mucin binding proved polyethylene glycol (PEG) and chitosan modified nanoparticles as potential candidates for oral mucosa delivery. Both showed highest OVA encapsulation at 67% and 73%, and sustained OVA release in SIF (96 h) at 65% and 64% respectively. BET results showed that nanopores were not blocked during surface modification. CD and SDS-PAGE showed that OVA conformational structure did not change after release from the nanoparticles.
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http://dx.doi.org/10.1016/j.xphs.2020.03.021DOI Listing
July 2020

Formation of stable nanoemulsions by ultrasound-assisted two-step emulsification process for topical drug delivery: Effect of oil phase composition and surfactant concentration and loratadine as ripening inhibitor.

Int J Pharm 2020 Feb 14;576:118952. Epub 2019 Dec 14.

Bavarian Polymer Institute, KeyLab "Electron and Optical Microscopy", University of Bayreuth, Germany.

Nanoemulsions are very interesting systems as they offer capacity to encapsulate both hydrophilic and lipophilic molecules in a single particle, as well as the controlled release of chemical moieties initially entrapped in the internal droplets. In this study, we propose a new two-step modified ultrasound-assisted phase inversion approaches-phase inversion temperature (PIT) and self-emulsification, to prepare stable o/w nanoemulsions from a fully water-dilutable microemulsion template for the transdermal delivery of loratadine (a hydrophobe and as Ostwald ripening inhibitor). Firstly, the primary water-in-oil microemulsion concentrate (w/o) was formed using loratadine in the oil phase (oleic acid or coconut oil) and Tween 80 in the aqueous phase and by adjusting the PIT around 85 °C followed by stepwise dilution with water at 25 °C to initiate the formation the nanoemulsions (o/w). To assure the long-term stability, a brief application of low frequency ultrasound was employed. Combining the two low energy methods resulted in nanoemulsions prepared by mixing constant surfactant/oil ratios above the PIT with varying water volume fraction (self-emulsification) during the PIT by stepwise dilution. The kinetic stability was evaluated by measuring the droplet size with time by dynamic light scattering (DLS). The droplet size ranged 15-43 nm and did not exceed 100 nm over the period of 6 months indicating the system had high kinetic stability. Cryo-TEM showed that the nanoemulsions droplets were monodispersed and approaching micellar structure and scale. All nanoemulsions had loratadine crystals formed within 20 days after preparation, which tended to sediment during storage. Nanoemulsions improved the in vitro permeation of loratadine through porcine skin up to 20 times compared to the saturated solution.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118952DOI Listing
February 2020

Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films.

Int J Pharm X 2019 Dec 23;1:100033. Epub 2019 Aug 23.

School of Science, Faculty of Engineering and Science, University of Greenwich (Medway Campus), Chatham Maritime, Kent ME4 4TB, UK.

Changes in tensile properties and the glass transition temperature (T) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the T on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and T of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (T') well below (113 to 127 °C) the bulk T. The relaxation times (τ) were 71 ± 1, 46 ± 1, 42 ± 1, 36 ± 1 and 29 ± 1 s for HPMC films containing 0, 6, 8, 11 and 17% (w/w) PEG, respectively. The T and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, T and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries.
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http://dx.doi.org/10.1016/j.ijpx.2019.100033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744590PMC
December 2019

Comparison and process optimization of PLGA, chitosan and silica nanoparticles for potential oral vaccine delivery.

Ther Deliv 2019 08 9;10(8):493-514. Epub 2019 Sep 9.

School of Science, Faculty of Engineering & Science, University of Greenwich, Medway, Kent, ME4 4TB, UK.

The study compared performance of nanoparticles prepared from synthetic organic, natural organic and inorganic materials as vaccine delivery platforms. Various formulation (concentration, polymer/silica:surfactant ratio, solvent) and process parameters (homogenization speed and time, ultrasonication) affecting functional performance characteristics of poly(lactic--glycolic acid) (PLGA), chitosan and silica-based nanoparticles containing bovine serum albumin were investigated. Nanoparticles were characterized using dynamic light scattering, x-ray diffraction, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy and protein release. Critical formulation parameters were surfactant concentration (PLGA, silica) and polymer concentration (chitosan). Optimized nanoparticles were spherical in shape with narrow size distribution and size ranges of 100-300 nm (blank) and 150-400 nm (protein loaded). Protein encapsulation efficiency was 26-75% and released within 48 h in a sustained manner. Critical formulation and process parameters affected size of PLGA, chitosan and silica nanoparticles and protein encapsulation, while silica produced the smallest and most stable nanoparticles.
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http://dx.doi.org/10.4155/tde-2019-0038DOI Listing
August 2019

Oral thin films as a remedy for noncompliance in pediatric and geriatric patients.

Ther Deliv 2019 07 2;10(7):443-464. Epub 2019 Jul 2.

School of Science, University of Greenwich, Medway Campus, Kent, ME4 4TB, UK.

Pediatric and geriatric patients experience swallowing difficulties for traditional oral dosage forms, such as tablets. Further, microbial contamination, chemical stability, unpleasant taste and swallowing large volumes of fluids have led to low therapeutic efficacy and patient noncompliance. The emergence of oral thin films has resulted in dramatic improvements in compliance and drug therapy outcomes in pediatric and geriatric patients. Oral thin films do not require water for administration, are readily hydrated upon contact with saliva, adhere to the mucosa and disintegrate ideally under 1 min. This article provides an overview of oral thin films, modern trends in their formulation and characterization, available commercial products, information to fill knowledge gaps and future potential and economic prospects of oral thin film technology, with emphasis on their use in the pediatric and geriatric patient groups.
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http://dx.doi.org/10.4155/tde-2019-0032DOI Listing
July 2019

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma.

Int J Pharm 2019 Jul 23;566:111-125. Epub 2019 May 23.

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent ME4 4TB, United Kingdom. Electronic address:

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.
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http://dx.doi.org/10.1016/j.ijpharm.2019.05.059DOI Listing
July 2019

Composite Biopolymer-Based Wafer Dressings Loaded with Microbial Biosurfactants for Potential Application in Chronic Wounds.

Polymers (Basel) 2018 Aug 15;10(8). Epub 2018 Aug 15.

Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Kent ME4 4TB, UK.

In this study two bioactive polysaccharide polymers -carrageenan (CARR) and sodium alginate (SA) incorporated with microbial biosurfactants (BSs) were formulated as medicated wafer dressings for potential application in chronic wounds. Wafers were loaded with BSs at concentrations of 0.1% and 0.2% rhamnolipids (RL) and 0.1% and 5% sophorolipids (SL) and were functionally characterized using scanning electron microscopy (SEM), texture analysis (mechanical strength and in vitro wound adhesion), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD) and exudate handling properties (pore analysis, swelling index, water absorption (w), equilibrium water content (), evaporative water loss (EWL) and water vapor transmission rate (WVTR). The wafers were tactile and ductile in appearance with a hardness range of 2.7⁻4.1 N and can withstand normal stresses but are also flexible to prevent damage to newly formed skin tissues. Wafers were porous (SEM) with pore sizes ranging from 78.8 to 141 µm, and BSs were not visible on the wafer surface or pore walls. The BSs enhanced the porosity of the wafers with values above 98%, while the w and ranged from 2699⁻3569% and 96.58⁻98.00%, respectively. The EWL ranged from 85 to 86% after 24 h while the WVTR ranged from 2702⁻3080 g/m² day. The compatibility of BSs within the CARR-SA matrix was confirmed by seven characteristic functional groups which were consistently transmitted in the ATR-FTIR spectra. These novel medicated dressing prototypes can potentially help to achieve more rapid wound healing.
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http://dx.doi.org/10.3390/polym10080918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403717PMC
August 2018

Evaluation of Clay-Functionalized Wafers and Films for Nicotine Replacement Therapy via Buccal Mucosa.

Pharmaceutics 2019 Mar 1;11(3). Epub 2019 Mar 1.

School of Science, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.

The functional physicochemical properties of nicotine (NIC)-loaded composite freeze-dried wafers and solvent-evaporated films comprising hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA), stabilized with magnesium aluminium silicate (MAS), have been reported. The formulations were characterized for swelling capacity, mucoadhesion, in vitro drug dissolution properties in simulated saliva (SS) and PBS at pH 6.8, and ex vivo and in vitro permeation using pig buccal mucosa membrane and EpiOral buccal tissue culture, respectively; finally, the cell viability of the EpiOral tissues after contact with the NIC-loaded formulations was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the functional characteristics compared with those of commercially available NIC strips. Swelling and NIC release from the HPMC⁻SA wafers were more prolonged (30 min) compared to the commercially available NIC strips which disintegrated rapidly and released the drug within 5 min. Generally, swelling, mucoadhesion, and drug release was faster in PBS than in SS, and the presence of MAS was essential for maintaining a high dose recovery compared to non-MAS formulations and commercial NIC strips, which showed lower percentage of NIC content, possibly due to evaporation during analysis. Permeation studies showed that the NIC released was able to cross both porcine buccal membrane and the EpiOral buccal tissue, with the latter showing higher permeation flux for all the formulations tested. All the NIC-loaded, MAS-stabilized formulations showed high tissue viability, with values above 80%, showing their great potential for use as buccal delivery platforms for NIC replacement therapy to aid smoking cessation.
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http://dx.doi.org/10.3390/pharmaceutics11030104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471811PMC
March 2019

3D printed chitosan dressing crosslinked with genipin for potential healing of chronic wounds.

Int J Pharm 2019 Apr 21;560:406-415. Epub 2019 Feb 21.

School of Science, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK. Electronic address:

Recently, various additive manufacturing (3D printing) approaches have been employed to fabricate dressings such as film scaffolds that possess well defined architecture and orientation at the micro level. In this study, crosslinked chitosan (CH) based film matrices were prepared using 3D printing with genipin (GE) as a crosslinker, with glycerol (GLY) and poly ethylene glycol (PEG) as plasticizer. The 3D printed films were functionally characterized using (tensile, fluid handling, mucoadhesion, drug dissolution, morphological properties and cell viability as well physico-chemical characterization using scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. CH-GE-PEG600 3D printed films having the ratio of 1:1 polymer: plasticizer was selected due to their appropriate flexibility. Fourier transform infrared results showed intermolecular interaction between CH, GE and PEG which was confirmed by X-ray diffraction showing amorphous matrix structure. In vitro mucoadhesion studies of CH-GE-PEG600 films showed the capability of the 3D printed film to adhere to the epithelial surface. Scanning electron microscopy images showed that the surface of the plasticised films were smooth indicating content uniformity of CH, GE and PEG whilst micro cracks in unplasticised films confirmed their brittle nature. Plasticised films also showed high swelling capacity which enhanced water absorption. Cytotoxicity (MTT) assay using human skin fibroblast cell lines demonstrated that more than 90% of cells were viable after 48 h confirming non-toxic nature of the 3D printed CH-GE-PEG600 films and therefore promising dressing for chronic wound healing applications.
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http://dx.doi.org/10.1016/j.ijpharm.2019.02.020DOI Listing
April 2019

A Preliminary Study of Pain Relieving Dressings for Older Adults With Chronic Leg Ulcers From the Provider's Perspective: A Qualitative Study.

J Pain Palliat Care Pharmacother 2018 Jun - Sep;32(2-3):71-81. Epub 2018 Dec 27.

Prevalence of leg ulcers increases with age due to an increase in risk factors, including immobility and venous disease. With an increasingly aging population, therefore, the number of older adults with leg ulcers is increasing. Older adults with leg ulcers experience frequent pain and discomfort, and yet pain in this population is poorly managed. The aim of this study was to explore the feasibility of the use of analgesic dressings in older adults with leg ulcers, including their perception of current pain management, feasibility of an analgesic dressing, and potential challenges. The overriding objective was to use the information to design a novel advanced dressing that is highly effective and acceptable to patients and health professionals at affordable cost. Focus groups involving nurses, with experience of leg ulcers, were conducted. Participants were asked their opinion on pain from leg ulcers, including perception of current pain management, feasibility of an analgesic dressing, and potential challenges of using analgesia in this format. Focus groups and interviews were recorded and transcribed verbatim and analyzed using a framework approach. Fifteen nurses attended two focus groups and one older adult completed a telephone interview. The overall opinion of an analgesic dressing were very positive; the key themes relating to the use of an analgesic dressing in practice include duration of pain relief; when pain occurs; type of analgesic; skin integrity; training/experience; compliance; and dressing practicalities. Leg ulcers are well known to be painful and often associated with social stigma. A dressing that deals with absorption issues and can help to manage pain, particularly during dressing changes (when pain is highest), would be welcomed by nurse professionals. This preliminary study provides a basis upon which future research can be based.
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http://dx.doi.org/10.1080/15360288.2018.1527801DOI Listing
August 2019

The Challenges and Knowledge Gaps in Malaria Therapy: A Stakeholder Approach to Improving Oral Quinine Use in the Treatment of Childhood Malaria in Ghana.

J Pharm (Cairo) 2018 14;2018:1784645. Epub 2018 Nov 14.

Department of Pharmaceutics, Kwame Nkrumah University of Science & Technology, Kumasi, Ghana.

Background: The study was undertaken to elicit the knowledge, views, and perceptions of key stakeholders on malaria, its bioburden, and treatment options, in order to ascertain the knowledge gabs and challenges, especially in the use of oral quinine in childhood malaria.

Methods: A cross-sectional survey was conducted using a well-structured Likert Scale and self-administered questionnaire. The principal site of the study was a government-run children's hospital located in the Ashiedu Keteke Sub-Metro of Accra. The study population included health workers, parents, and guardians or care givers. The participants were 300, purposively selected, and consisted of both men (41%) and women (59%) who were twenty years and above, whether employed (42%), self-employed (37%), or unemployed (21%).

Results: Majority of the participants (78%) demonstrated above average knowledge of malaria. However, their awareness of the causes, modes of transmission, signs, and symptoms as well as preventive mechanisms of malaria did not result in low incidence of malaria. About 77% of the respondents agreed they would seek treatment within 24 hours once signs and symptoms are detected. Though close to 50% undertook home treatment of malaria, majority eventually sought treatment at hospital or clinic. Above 92% of respondents knew that quinine is used to treat malaria and agreed its bitter taste greatly affects compliance, especially in children. Consequently, 95% of the respondents would be glad if its bitter taste is masked.

Conclusion: The study demonstrated the availability of substantial knowledge of the devastating effects of malaria, especially in children. Therefore, there is the need to ensure the availability and utilization of effective paediatric formulations in the fight against malaria. From this study, fast dissolving oral thin film with a good mouth feel, would be the formulation of choice for quinine.
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http://dx.doi.org/10.1155/2018/1784645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261397PMC
November 2018

Development and functional characterization of composite freeze dried wafers for potential delivery of low dose aspirin for elderly people with dysphagia.

Int J Pharm 2018 Dec 9;553(1-2):65-83. Epub 2018 Oct 9.

Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK. Electronic address:

The impact of demographic ageing is likely to be of major significance in the coming decades due to low birth rates and higher life expectancy. Older people generally require more prescribed medicines due to the presence of multiple conditions such as dysphagia which can make swallowing medicines challenging. This study involves the development, characterization and optimization of composite wafers for potential oral and buccal delivery of low dose aspirin to prevent thrombosis in elderly patients with dysphagia. Blank (BLK) wafers (no loaded drug) were initially formulated by dissolving combinations of metolose (MET) with carrageenan (CAR) and MET with low molecular weight chitosan (CS) in different weight ratios in water, to identify optimum polymer combinations. However, drug loaded (DL) wafers were prepared using 45% v/v ethanol to help complete solubilization of the aspirin. The formulations were characterized using texture analyzer (hardness, mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), attenuated total reflectance - Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA), and swelling capacity. Wafers with higher total polymer concentration were more resistant to penetration (MET:CAR 1:1 samples B2, C2) and MET:CS 1:1 (sample E2) and MET:CS 3:1 (sample F2) and also depended on the ratios between the polymers used. From the characterization, samples C2, B2, E2 and F2 showed the most ideal characteristics. XRD showed that BLK wafers were amorphous, whilst the DL wafers were crystalline due to the presence of aspirin. SEM confirmed the presence of pores within the polymer matrix of the BLK wafers, whilst DL wafers showed a more compact polymeric matrix with aspirin dispersed over the surface. The DL wafers showed a good flexibility required for transportation and patient handling and showed higher swelling capacity and adhesion values with phosphate buffer saline (PBS) than with simulated saliva (SS). Drug dissolution studies showed that aspirin was rapidly released in the first 20 min and then continuously over 1 h. FTIR confirmed the interaction of aspirin with the polymers evidenced by peak shifts around 1750 cm and the broad peak between 2500 and 3300 cm. Lyophilized CAR: CS 1:3 (sample DL13), MET:CS 1:3 (sample DL8) and MET:CAR 3:1 (sample DL1) wafers seem to be a very promising system for the administration of low dose aspirin for older patients with dysphagia.
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http://dx.doi.org/10.1016/j.ijpharm.2018.10.025DOI Listing
December 2018

Comparison of in vitro antibacterial activity of streptomycin-diclofenac loaded composite biomaterial dressings with commercial silver based antimicrobial wound dressings.

Int J Biol Macromol 2019 Jan 6;121:191-199. Epub 2018 Oct 6.

Department of Pharmaceutical, Chemical & Environmental Sciences, School of Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, ME4 4TB Kent, UK. Electronic address:

Infected chronic wounds heal slowly, exhibiting prolonged inflammation, biofilm formation, bacterial resistance, high exudate and ineffectiveness of systemic antimicrobials. Composite dressings (films and wafers) comprising polyox/carrageenan (POL-CAR) and polyox/sodium alginate (POL-SA), loaded with diclofenac (DLF) and streptomycin (STP) were formulated and tested for antibacterial activity against 2 × 10 CFU/mL of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus representing infected chronic wounds and compared with marketed silver dressings. Minimum inhibitory concentration (MIC) showed higher values for DLF than STP due to non-conventional antibacterial activity of DLF. The DLF and STP loaded dressings were highly effective against E. coli, P. aeruginosa and S. aureus. POL-SA dressings were more effective against the three types of bacteria compared to POL-CAR formulations, while the DLF and STP loaded dressings showed greater antibacterial activity than the silver-based dressings. The films, showed greater antibacterial efficacy than both wafers and silver dressings. STP and DLF can act synergistically not only to kill the bacteria but also prevent their resistance and biofilm formation compared to silver dressings, while reducing chronic inflammation associated with infection.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.10.023DOI Listing
January 2019

3D printed microneedles for insulin skin delivery.

Int J Pharm 2018 Jun 16;544(2):425-432. Epub 2018 Mar 16.

Faculty of Engineering & Sciences, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, Chatham, Kent ME4 4TB, United Kingdom. Electronic address:

In this study, polymeric microneedle patches were fabricated by stereolithography, a 3D printing technique, for the transdermal delivery of insulin. A biocompatible resin was photopolymerized to build pyramid and cone microneedle designs followed by inkjet print coating of insulin formulations. Trehalose, mannitol and xylitol were used as drug carriers with the aim to preserve insulin integrity and stability but also to facilitate rapid release rates. Circular dichroism and Raman analysis demonstrated that all carriers maintained the native form of insulin, with xylitol presenting the best performance. Franz cell release studies were used for in vitro determination of insulin release rates in porcine skin. Insulin was released rapidly within 30 min irrespectively of the microneedle design. 3D printing was proved an effective technology for the fabrication of biocompatible and scalable microneedle patches.
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http://dx.doi.org/10.1016/j.ijpharm.2018.03.031DOI Listing
June 2018

Calcium alginate-based antimicrobial film dressings for potential healing of infected foot ulcers.

Ther Deliv 2018 02;9(3):185-204

Department of Pharmaceutical, Chemical & Environmental Sciences, Faculty of Engineering & Science, University of Greenwich, Medway, Central Ave Chatham Maritime, Kent, ME4 4TB, UK.

Aim: Diabetic foot ulcers are susceptible to infection and nonmedicated dressings are ineffective because they have no antimicrobial activity. This study aimed to develop antimicrobial films to deliver ciprofloxacin for treating bacterial infection. Results/methodology: Ciprofloxacin-loaded calcium alginate films were characterized for porosity, swelling, equilibrium water content, water absorption, water vapor transmission, evaporative water loss, moisture content, mechanical strength, adhesion, IR spectroscopy, scanning electron microscopy, x-ray diffraction, drug release, cytotoxicity and antimicrobial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Films were transparent, flexible, uniform, with ideal moisture handling, maximum drug release within 90 min, killing bacteria within 24 h and highly biocompatible with human keratinocyte cells.

Conclusion: The results confirmed successful design of biocompatible dressings effective against Gram-positive and Gram-negative bacteria. [Formula: see text].
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http://dx.doi.org/10.4155/tde-2017-0104DOI Listing
February 2018

Effects of Cyclodextrins (β and γ) and l-Arginine on Stability and Functional Properties of Mucoadhesive Buccal Films Loaded with Omeprazole for Pediatric Patients.

Polymers (Basel) 2018 Feb 7;10(2). Epub 2018 Feb 7.

Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.

Omeprazole (OME) is employed for treating ulcer in children, but is unstable and exhibits first pass metabolism via the oral route. This study aimed to stabilize OME within mucoadhesive metolose (MET) films by combining cyclodextrins (CD) and l-arginine (l-arg) as stabilizing excipients and functionally characterizing for potential delivery via the buccal mucosa of paediatric patients. Polymeric solutions at a concentration of 1% / were obtained by dispersing the required weight of metolose in 20% / ethanol as solvent at a temperature of 40 °C using polyethylene glycol (PEG 400) (0.5% /) as plasticizer. The films were obtained by drying the resulting polymer solutions at in an oven at 40 °C. Textural (tensile and mucoadhesion) properties, physical form (differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy), residual moisture content (thermogravimetric analysis (TGA)) and surface morphology (scanning electron microscopy (SEM)) were investigated. Optimized formulations containing OME, CDs (β or γ) and l-arg (1:1:1) were selected to investigate the stabilization of the drug. The DSC, XRD, and FTIR showed possible molecular dispersion of OME in metolose film matrix. Plasticized MET films containing OME:βCD:l-arg 1:1:1 were optimum in terms of transparency and ease of handling and therefore further functionally characterized (hydration, mucoadhesion, in vitro drug dissolution and long term stability studies). The optimized formulation showed sustained drug release that was modelled by Korsmeyer⁻Peppas equation, while the OME showed stability under ambient temperature conditions for 28 days. The optimized OME loaded MET films stabilized with βCD and l-arg have potential for use as paediatric mucoadhesive buccal delivery system, which avoids degradation in the stomach acid as well as first pass metabolism in the liver.
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http://dx.doi.org/10.3390/polym10020157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415044PMC
February 2018

Ciprofloxacin-loaded calcium alginate wafers prepared by freeze-drying technique for potential healing of chronic diabetic foot ulcers.

Drug Deliv Transl Res 2018 12;8(6):1751-1768

Department of Pharmaceutical, Chemical & Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway, Central Ave. Chatham Maritime, Kent, ME4 4TB, UK.

Calcium alginate (CA) wafer dressings were prepared by lyophilization of hydrogels to deliver ciprofloxacin (CIP) directly to the wound site of infected diabetic foot ulcers (DFUs). The dressings were physically characterized by scanning electron microscopy (SEM), texture analysis (for mechanical and in vitro adhesion properties), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Further, functional properties essential for wound healing, i.e., porosity, in vitro swelling index, water absorption (Aw), equilibrium water content (EWC), water vapor transmission rate (WVTR), evaporative water loss (EWL), moisture content, in vitro drug release and kinetics, antimicrobial activity, and cell viability (MTT assay) were investigated. The wafers were soft, of uniform texture and thickness, and pliable in nature. Wafers showed ideal wound dressing characteristics in terms of fluid handling properties due to high porosity (SEM). XRD confirmed crystalline nature of the dressings and FTIR showed hydrogen bond formation between CA and CIP. The dressings showed initial fast release followed by sustained drug release which can inhibit and prevent re-infection caused by both Gram-positive and Gram-negative bacteria. The dressings also showed biocompatibility (> 85% cell viability over 72 h) with human adult keratinocytes. Therefore, it will be a potential medicated dressing for patients with DFUs infected with drug-resistant bacteria.
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http://dx.doi.org/10.1007/s13346-017-0445-9DOI Listing
December 2018

Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

J Pharm Sci 2018 02 5;107(2):654-661. Epub 2017 Oct 5.

Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, Naples 80131, Italy.

The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders.
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http://dx.doi.org/10.1016/j.xphs.2017.09.026DOI Listing
February 2018

Drug Delivery Innovations to Address Global Health Challenges for Pediatric and Geriatric Populations (Through Improvements in Patient Compliance).

Authors:
Joshua Boateng

J Pharm Sci 2017 11 20;106(11):3188-3198. Epub 2017 Jul 20.

Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK. Electronic address:

Despite significant advances in pharmaceutical and biotechnological drug discovery, the global population is plagued with many challenging diseases. These are further compounded by anticipated explosion in an ageing population, which presents several problems such as polypharmacy, dysphagia, and neurologic conditions, resulting in noncompliance and disease complications. For antibiotics, poor compliance, can result in development of drug-resistant infections which can be fatal. Furthermore, children, especially, in developing countries die unnecessarily from easily treatable diseases (e.g., malaria), due to poor compliance arising from bitter taste and inability to swallow currently available medication. Although some of these challenges require the discovery of new drug compounds, a significant number can be resolved by employing pharmaceutics approaches to reduce the incidence of poor patient compliance. Such solutions are expected to make swallowing easier and reduce the need to swallow several solid medications, which is difficult for vulnerable pediatric and geriatric patients. This commentary will explore the current state of the art in the use of drug delivery innovations to overcome some of these challenges, taking cues from relevant regulatory agencies such as the Food and Drug Administration, the European Medicines Agency, World Health Organization, and the peer-reviewed scientific and clinical literature.
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http://dx.doi.org/10.1016/j.xphs.2017.07.009DOI Listing
November 2017

Advanced multi-targeted composite biomaterial dressing for pain and infection control in chronic leg ulcers.

Carbohydr Polym 2017 Sep 15;172:40-48. Epub 2017 May 15.

Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK. Electronic address:

This study aimed to develop advanced biomaterial polysaccharide based dressings to manage pain associated with infected chronic leg ulcers in older adults. Composite carrageenan (CARR) and hyaluronic acid (HA) dressings loaded with lidocaine (LID) and AgNPs were formulated as freeze-dried wafers and functionally characterized for porous microstructure (morphology), mechanical strength, moisture handling properties, swelling, adhesion and LID release. Antimicrobial activity of AgNPs was evaluated (turbidity assay) against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus whilst cell viability studies (MTT) was performed on normal adult human primary epidermal keratinocyte cells. The wafers were soft, flexible and elegant in appearance. HA affected the wafer structure by increasing the resistance to compression but still possessed a balance between toughness and flexibility to withstand normal stresses and prevent damage to newly formed skin tissue respectively. Water uptake was influenced by HA, whilst equilibrium water content and LID release were similar for all the formulations, showing controlled release up to 6h. AgNPs loaded CARR/HA wafers were effective in inhibiting the growth of both Gram positive and Gram negative bacteria. MTT assay showed evidence that the AgNPs/LID loaded wafers did not interfere with cell viability and growth. CARR/HA wafers seem to be a promising system to simultaneously deliver LID and AgNPs, directly to infected chronic leg ulcers.
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http://dx.doi.org/10.1016/j.carbpol.2017.05.040DOI Listing
September 2017

Nicotine stabilization in composite sodium alginate based wafers and films for nicotine replacement therapy.

Carbohydr Polym 2017 Jan 18;155:78-88. Epub 2016 Aug 18.

Department of Pharmaceutical Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, ME4 4TB, Kent, UK. Electronic address:

Composite wafers and films comprising HPMC and sodium alginate (SA) were formulated for nicotine (NIC) replacement therapy via the buccal route. Magnesium aluminium silicate (MAS) was added in different concentration ratios (0.25, 0.5, 0.75) to stabilize NIC and its effect on mechanical properties, internal and surface morphology, physical form, thermal properties, swelling, mucoadhesion, drug content and release behaviour of the formulations was investigated. MAS changed the physico-mechanical properties of the composite formulations causing a decrease in mechanical hardness, collapsed wafer pores, increased roughness of film surface, increase in crystallinity and decreased mucoadhesion of the wafers. However, MAS increased swelling in both films and wafers as well as interaction between NIC and SA, which increased drug-loading capacity. Further, MAS resulted in rapid and slow release of NIC from wafers and films respectively. The results suggest that the ideal formulation for the stabilization of NIC in the composite formulations was MAS 0.25.
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http://dx.doi.org/10.1016/j.carbpol.2016.08.053DOI Listing
January 2017

Conversion of sustained release omeprazole loaded buccal films into fast dissolving strips using supercritical carbon dioxide (scCO2) processing, for potential paediatric drug delivery.

Eur J Pharm Sci 2016 Oct 4;93:45-55. Epub 2016 Aug 4.

Department of Pharmaceutical, Chemical & Environmental Sciences, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, ME4 4TB Kent, UK. Electronic address:

This study involves the development of thin oral solvent cast films for the potential delivery of the proton pump inhibitor, omeprazole (OME) via the buccal mucosa for paediatric patients. OME containing films were prepared from ethanolic gels (1% w/w) of metolose (MET) with polyethylene glycol (PEG 400) (0.5% w/w) as plasticiser, and L-arginine (l-arg) (0.2% w/w) as a stabilizer and dried in an oven at 40°C. The blank and drug loaded films were divided into two groups, one group was subjected to supercritical carbon dioxide (scCO2) treatment and the other group untreated. The untreated and scCO2 treated films were then characterised using differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, hydration (swelling), mucoadhesion and in vitro drug dissolution studies. Treatment of the solvent cast films with scCO2 caused significant changes to the functional and physical properties of the MET films. The original drug loaded MET films showed a sustained release of OME (1h), whereas scCO2 treatment of the formulations resulted in fast dissolving films with >90% drug release within 15min.
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http://dx.doi.org/10.1016/j.ejps.2016.08.007DOI Listing
October 2016

Systematic comparison of the functional physico-chemical characteristics and biocidal activity of microbial derived biosurfactants on blood-derived and breast cancer cells.

J Colloid Interface Sci 2016 Oct 22;479:221-233. Epub 2016 Jun 22.

Faculty of Engineering and Science, University of Greenwich, Medway, Kent ME4 4TB, UK. Electronic address:

Hypothesis: The cytotoxicity of biosurfactants on cell membranes may be influenced by composition of their hydrophilic head and hydrophobic tails. It is hypothesised that they form mixed micelles which exert a detergent-like effect that disrupts the plasma membrane. The functional physico-chemical and biocidal characteristics of four biosurfactants were concurrently investigated to determine which of their structural characteristics may be tuned for greater efficacy.

Experiments: Rhamnolipid-95, rhamnolipid-90, surfactin and sophorolipid were characterised using FTIR, LC-MS, HPLC, surface tension and critical micelle concentration. Their biocidal activity against HEK 293, MCF-7 and THP-1 cell lines were investigated by MTT assay, using doxorubicin as cytotoxic control. Growth curves were established for all cell lines using trypan blue (TB) and MTT assays, corresponding doubling time (DT) and growth rate were obtained and compared.

Findings: HEK 293 cell-line had the highest growth rate amongst the three cell lines. For TB assay, growth of HEK 293>THP-1 and for MTT, HEK 293>MCF-7 while the DT was in the order of THP-1>MCF-7>HEK 293. Sophorolipid showed anti-proliferative activity comparable to doxorubicin on THP-1>MCF-7>HEK 293. THP-1 showed high sensitivity to sophorolipid with IC50 of 10.50, 25.58 and 6.78(μg/ml) after 24, 48 and 72h respectively. However, sophorolipid was cytotoxic from 24 to 72h on HEK 293 cell lines with IC50 of 21.53, 40.57 and 27.53μg/ml respectively. Although, doxorubicin showed higher anti-proliferative activity than all biosurfactants, it had poorer selectivity index for the same time durations compared to the biosurfactants. This indicates that biosurfactants were more effective for slowing the growth of the tested cancer cell lines and hence may be potential candidates for use in human cancer therapy. Physico-chemical characteristics of the biosurfactants suggest that their mechanism of action may be due to activity on the cell membrane.
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http://dx.doi.org/10.1016/j.jcis.2016.06.051DOI Listing
October 2016

Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

Int J Biol Macromol 2016 Oct 21;91:31-44. Epub 2016 May 21.

Department of Pharmaceutical Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, ME4 4TB Kent, UK. Electronic address:

Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.05.079DOI Listing
October 2016
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