Publications by authors named "Dimitrios A Lamprou"

77 Publications

3D and 4D Printing in the Fight against Breast Cancer.

Biosensors (Basel) 2022 Jul 26;12(8). Epub 2022 Jul 26.

School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

Breast cancer is the second most common cancer worldwide, characterized by a high incidence and mortality rate. Despite the advances achieved in cancer management, improvements in the quality of life of breast cancer survivors are urgent. Moreover, considering the heterogeneity that characterizes tumors and patients, focusing on individuality is fundamental. In this context, 3D printing (3DP) and 4D printing (4DP) techniques allow for a patient-centered approach. At present, 3DP applications against breast cancer are focused on three main aspects: treatment, tissue regeneration, and recovery of the physical appearance. Scaffolds, drug-loaded implants, and prosthetics have been successfully manufactured; however, some challenges must be overcome to shift to clinical practice. The introduction of the fourth dimension has led to an increase in the degree of complexity and customization possibilities. However, 4DP is still in the early stages; thus, research is needed to prove its feasibility in healthcare applications. This review article provides an overview of current approaches for breast cancer management, including standard treatments and breast reconstruction strategies. The benefits and limitations of 3DP and 4DP technologies are discussed, as well as their application in the fight against breast cancer. Future perspectives and challenges are outlined to encourage and promote AM technologies in real-world practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/bios12080568DOI Listing
July 2022

The sustainability of emerging technologies for use in pharmaceutical manufacturing.

Expert Opin Drug Deliv 2022 Jul 27;19(7):861-872. Epub 2022 Jun 27.

School of Pharmacy, Queen's University Belfast, Belfast, UK.

Introduction: Sustainability within the pharmaceutical industry is becoming a focal point for many companies, to improve the longevity and social perception of the industry. Both additive manufacturing (AM) and microfluidics (MFs) are continuously progressing, so are far from their optimization in terms of sustainability; hence, it is the aim of this review to highlight potential gaps alongside their beneficial features. Discussed throughout this review also will be an in-depth discussion on the environmental, legal, economic, and social particulars relating to these emerging technologies.

Areas Covered: Additive manufacturing (AM) and microfluidics (MFs) are discussed in depth within this review, drawing from up-to-date literature relating to sustainability and circular economies. This applies to both technologies being utilized for therapeutic and analytical purposes within the pharmaceutical industry.

Expert Opinion: It is the role of emerging technologies to be at the forefront of promoting a sustainable message by delivering plausible environmental standards whilst maintaining efficacy and economic viability. AM processes are highly customizable, allowing for their optimization in terms of sustainability, from reducing printing time to reducing material usage by removing supports. MFs too are supporting sustainability via reduced material wastage and providing a sustainable means for point of care analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17425247.2022.2093857DOI Listing
July 2022

Development of Geraniol-Loaded Liposomal Nanoformulations against Colonization in the Pig Gut.

J Agric Food Chem 2022 Jun 2;70(23):7004-7014. Epub 2022 Jun 2.

Faculty of Health and Applied Sciences (HAS), University of the West of, Coldharbour Ln, Bristol BS16 1QY, England.

is a global health threat, with pig production being one of the main sources of human salmonellosis. The current study investigated the antivirulence properties of geraniol for inhibiting the in vitro colonization of . The minimum inhibitory (MIC) and bactericidal concentrations (MBC) of geraniol against followed by the sub-MIC of geraniol were determined. Results provided clear evidence that geraniol at 1/8 MIC can be used as an effective, non-toxic antivirulence compound to inhibit virulence factors (motility, adhesion, and invasiveness) affecting the colonization of on IPEC-J2 cells. Additionally, the findings signified that microfluidics is an emerging technology suitable for the preparation of stable liposomes with a small size (<200 nm) and high encapsulation efficiency (EE) of up to 92.53%, which can act as effective carriers of geraniol into the pig gastrointestinal tract (GIT), targeting , preventing colonization, and thus increasing the safety of the food supply chain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.2c00910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204824PMC
June 2022

Comprehensive review on novel targets and emerging therapeutic modalities for pulmonary arterial Hypertension.

Int J Pharm 2022 Jun 2;621:121792. Epub 2022 May 2.

Department of General Surgery, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi 590 010, India.

Pulmonary Arterial Hypertension (PAH) is the progressive increase in mean pulmonary arterial pressure (mPAP) (≥20 mmHg at rest). Current treatment strategies include the drugs targeting at nitric oxide pathway, endothelin receptors, prostaglandin receptors, thromboxane receptors and phosphodiesterase inhibitors, which provides the symptomatic relief. Despite of these treatments, the mortality amongst the PAH patients remains high due to non-reversal of the condition. This review primarily covers the introduction of PAH and the current treatments of the disease. This is followed by the newer disease targets expressed in the pathobiology of the disease like Rho Kinase Pathway, Vasoactive Intestinal Peptide Pathway, Receptor Tyrosine Kinases, Serotonin signalling pathway, Voltage-gated potassium (Kv) channel pathway. Newer formulation strategies for targeting at these specific receptors were covered and includes nano formulations like liposomes, Micelles, Polymeric Nanoparticles, Solid Lipid Nanoparticles (SLN), Bioresorbable stents, NONOates, Cell-Based Therapies, miRNA therapy for PAH. Novel targets were identified for their role in the pathogenesis of the PAH and needs to be targeted with new molecules or existing molecules effectively. Nanosystems have shown their potential as alternative carriers on the virtue of their better performance than traditional drug delivery systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2022.121792DOI Listing
June 2022

Stereolithography 3D printed implants: A preliminary investigation as potential local drug delivery systems to the ear.

Int J Pharm 2022 Mar 1;616:121529. Epub 2022 Feb 1.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

The current study is a preliminary investigation on the use of stereolithography 3D printing technology in the field of personalized medicines and specifically for delivering drugs locally, which can for example usefully be applied to ear infections. The main aim is the development of drug-loaded implants for the treatment of ear diseases, to improve patient compliance and to overcome the limitations of current delivery approaches. Multiple prototypes of implant geometries have been created and printed using a flexible resin containing 0.5% w/v of Levofloxacin. Physicochemical characterization of the printed implants was carried out using a variety of techniques (e.g., microscopic, spectroscopic, and mechanical analysis). Finally, preliminary in vitro tests were performed to evaluate the release profile of Levofloxacin, the prototype implant's stability, and their antimicrobial property. The results obtained show that there is no interaction between the resin and the drug, which is perfectly solubilized in the device. In addition, the results of the mechanical tests show that the material used resists compression without compromising the design itself, and the diffusion test has shown that the drug diffused through the matrix prototype at 50% over 3 weeks. The selected designs showed higher antimicrobial activity on E. coli than on S. aureus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2022.121529DOI Listing
March 2022

3D bioprinted scaffolds for diabetic wound-healing applications.

Drug Deliv Transl Res 2022 Jan 11. Epub 2022 Jan 11.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13346-022-01115-8DOI Listing
January 2022

Microfluidics Technology for the Design and Formulation of Nanomedicines.

Nanomaterials (Basel) 2021 Dec 18;11(12). Epub 2021 Dec 18.

School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

In conventional drug administration, drug molecules cross multiple biological barriers, distribute randomly in the tissues, and can release insufficient concentrations at the desired pathological site. Controlling the delivery of the molecules can increase the concentration of the drug in the desired location, leading to improved efficacy, and reducing the unwanted effects of the molecules under investigation. Nanoparticles (NPs), have shown a distinctive potential in targeting drugs due to their unique properties, such as large surface area and quantum properties. A variety of NPs have been used over the years for the encapsulation of different drugs and biologics, acting as drug carriers, including lipid-based and polymeric NPs. Applying NP platforms in medicines significantly improves the disease diagnosis and therapy. Several conventional methods have been used for the manufacturing of drug loaded NPs, with conventional manufacturing methods having several limitations, leading to multiple drawbacks, including NPs with large particle size and broad size distribution (high polydispersity index), besides the unreproducible formulation and high batch-to-batch variability. Therefore, new methods such as microfluidics (MFs) need to be investigated more thoroughly. MFs, is a novel manufacturing method that uses microchannels to produce a size-controlled and monodispersed NP formulation. In this review, different formulation methods of polymeric and lipid-based NPs will be discussed, emphasizing the different manufacturing methods and their advantages and limitations and how microfluidics has the capacity to overcome these limitations and improve the role of NPs as an effective drug delivery system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano11123440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707902PMC
December 2021

Microfluidic-mediated self-assembly of phospholipids for the delivery of biologic molecules.

Int J Pharm 2022 Jan 7;611:121347. Epub 2021 Dec 7.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

The encapsulation of biologic molecules using a microfluidic platform is a procedure that has been understudied but shows great promise from initial reported studies. The study focusses upon the encapsulation of bovine serum albumin (BSA) under various parameters and using multiple phospholipids to identify optimal conditions for the manufacturing of protein loaded lipid nanoparticles. Additionally, encapsulation of the enzyme trypsin (TRP) has been investigated to show the eligibility of the system to other biological medications. All liposomes were subject to rigorous physicochemical characterisation, including differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR), to document the successful synthesis of the liposomes. Drug-loaded liposome stability was investigated over a 28-day period at 5 °C and 37 °C, which showed encouraging results for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at all concentrations of BSA used. The sample containing 1 mg/ml BSA grew by only 10% over the study, which considering liposomes should be affected highly by biologic adsorption, shows great promise for the formulations. Encapsulation and in vitro release studies showed improved loading capacity for BSA compared to conventional methods, whilst maintaining a concise controlled release of the active pharmaceutical ingredient (API).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.121347DOI Listing
January 2022

Melt-extrusion 3D printing of resorbable levofloxacin-loaded meshes: Emerging strategy for urogynaecological applications.

Mater Sci Eng C Mater Biol Appl 2021 Dec 26;131:112523. Epub 2021 Oct 26.

Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Jordanstown Campus -, Newtownabbey BT37 0QB, UK. Electronic address:

Current surgical strategies for the treatment of pelvic floor dysfunctions involve the placement of a polypropylene mesh into the pelvic cavity. However, polypropylene meshes have proven to have inadequate mechanical properties and have been associated to the arising of severe complications, such as infections. Furthermore, currently employed manufacturing strategies are unable to produce compliant and customisable devices. In this work, polycaprolactone has been used to produce resorbable levofloxacin-loaded meshes in two different designs (90° and 45°) via melt-extrusion 3D printing. Drug-loaded meshes were produced using a levofloxacin concentration of 0.5% w/w. Drug loaded meshes were successfully produced with highly reproducible mechanical and physico-chemical properties. Tensile test results showed that drug-loaded 45° meshes possessed a mechanical behaviour close to that of the vaginal tissue (E ≃ 8.32 ± 1.85 MPa), even after 4 weeks of accelerated degradation. Meshes released 80% of the loaded levofloxacin in the first 3 days and were capable of producing an inhibitory effect against S. Aureus and E. coli bacterial strains with an inhibition zone equal to 12.8 ± 0.45 mm and 15.8 ± 0.45 mm respectively. Thus, the strategy adopted in this work holds great promise for the manufacturing of custom-made surgical meshes with antibacterial properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112523DOI Listing
December 2021

Optimization of Printing Parameters for Digital Light Processing 3D Printing of Hollow Microneedle Arrays.

Pharmaceutics 2021 Nov 2;13(11). Epub 2021 Nov 2.

School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

3D printing is an emerging technology aiming towards personalized drug delivery, among many other applications. Microneedles (MN) are a viable method for transdermal drug delivery that is becoming more popular for delivery through the skin. However, there is a need for a faster fabrication process with potential for easily exploring different geometries of MNs. In the current study, a digital light processing (DLP) method of 3D printing for fabrication of hollow MN arrays using commercial UV curable resin was proposed. Print quality was optimised by assessing the effect of print angle on needle geometries. Mechanical testing of MN arrays was conducted using a texture analyser. Angled prints were found to produce prints with geometries closer to the CAD designs. Curing times were found to affect the mechanical strength of MNs, with arrays not breaking when subjected to 300 N of force but were bent. Overall, DLP process produced hollow MNs with good mechanical strength and depicts a viable, quick, and efficient method for the fabrication of hollow MN arrays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics13111837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622592PMC
November 2021

Fused deposition modelling 3D printing proof-of-concept study for personalised inner ear therapy.

J Pharm Pharmacol 2021 Oct 19. Epub 2021 Oct 19.

School of Pharmacy, Queen's University Belfast, Belfast, UK.

Objectives: There is a requirement within ear therapeutics for a delivery system capable of safely delivering controlled doses to the inner ear. However, the anatomy and sensitivity of the inner ear make current delivery systems problematic and often ineffective. Therefore, a new delivery system is required to overcome these issues and provide a more efficacious system in the treatment of inner ear disease. This study assesses the potential of 3D printing (3DP) as a fabrication method for an implantable drug delivery system (DDS) to the inner ear.

Key Findings: Three implantable designs of varying geometry were produced with fused deposition modelling (FDM) 3DP, each loaded with 0.25%, 0.5% and 1% levofloxacin; filaments prepared by hot-melt extrusion. Each implant was effective in providing sustained, therapeutic release of levofloxacin for at least 4 days and as such would be effective in therapeutic treatment of many common inner ear diseases, such as otitis media or Ménière's disease.

Conclusions: This proof-of-concept research was successful in utilising FDM as a fabrication method for a DDS capable of providing prolonged release directly to the inner ear and highlights the viability of 3DP in the fabrication of an inner ear DDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpp/rgab147DOI Listing
October 2021

Optimization of FDM 3D printing process parameters to produce haemodialysis curcumin-loaded vascular grafts.

Drug Deliv Transl Res 2021 Oct 12. Epub 2021 Oct 12.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.

3D printing has provided a new prospective in the manufacturing of personalized medical implants, including fistulas for haemodialysis (HD). In the current study, an optimized fused modelling deposition (FDM) 3D printing method has been validated, for the first time, to obtain cylindrical shaped fistulas. Printing parameters were evaluated for the manufacturing of fistulas using blank and 0.25% curcumin-loaded filaments that were produced by hot melt extrusion (HME). Four different fistula types have been designed and characterized using a variety of physicochemical characterization methods. Each design was printed three times to demonstrate printing process accuracy considering outer and inner diameter, wall thickness, width, and length. A thermoplastic polyurethane (TPU) biocompatible elastomer was chosen, showing good mechanical properties with a high elastic modulus and maximum elongation, as well as stability at high temperatures with less than 0.8% of degradation at the range between 25 and 250 °C. Curcumin release profile has been evaluated in a saline buffer, obtaining a low release (12%) and demonstrating drug could continue release for a longer period, and for as long as grafts should remain in patient body. Possibility to produce drug-loaded grafts using one-step method as well as 3D printing process and TPU filaments containing curcumin printability has been demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13346-021-01078-2DOI Listing
October 2021

Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing.

Mater Sci Eng C Mater Biol Appl 2021 Oct 14;129:112375. Epub 2021 Aug 14.

School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK. Electronic address:

Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505756PMC
October 2021

3D Printing: an appealing technology for the manufacturing of solid oral dosage forms.

J Pharm Pharmacol 2021 Sep 16. Epub 2021 Sep 16.

School of Pharmacy, Queen's University Belfast, Belfast, UK.

Objectives: The traditional manufacturing methods of solid oral dosage forms (SODFs) are reported to be time-consuming, highly expensive and not tailored to the patient's needs. Three-dimensional printing (3DP) is an innovative emerging technology that can help to overcome these issues. The aim of this review is to describe the most employed 3DP technologies, materials and the state of the art on 3DP SODFs. Characterization techniques of 3DP SODFs, challenges and regulatory issues are also discussed.

Key Findings: The interest in the investigation of the suitability of 3DP as an alternative strategy for the fabrication of SODFs is growing. Different 3DP technologies and starting materials have been investigated for the development of SODFs. Numerous SODFs with complex geometries and composition, and with different release patterns, have been successfully manufactured via 3DP. Despite that, just one 3DP SODF has reached the market.

Summary: 3DP can be a promising alternative to the classical SODFs manufacturing methods. However, numerous technically and regulatory challenges still need to be addressed in order 3DP to be extensively used in the pharmaceutical sector.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpp/rgab136DOI Listing
September 2021

Frog nest foams exhibit pharmaceutical foam-like properties.

R Soc Open Sci 2021 Sep 8;8(9):210048. Epub 2021 Sep 8.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from predators and parasites, to prevent desiccation, to control gaseous exchange, to buffer temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time that nests of the túngara frog () are stable with useful physiochemical and biocompatible properties and are capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as topical drug delivery systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsos.210048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424294PMC
September 2021

Recent advances in electrospun nanofiber vaginal formulations for women's sexual and reproductive health.

Int J Pharm 2021 Sep 24;607:121040. Epub 2021 Aug 24.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

Electrospinning is an innovative technique that allows production of nanofibers and microfibers by applying a high voltage to polymer solutions of melts. The properties of these fibers - which include high surface area, high drug loading capacity, and ability to be manufactured from mucoadhesive polymers - may be particularly useful in a myriad of drug delivery and tissue engineering applications. The last decade has witnessed a surge of interest in the application of electrospinning technology for the fabrication of vaginal drug delivery systems for the treatment and prevention of diseases associated with women's sexual and reproductive health, including sexually transmitted infections (e.g. infection with human immunodeficiency virus and herpes simplex virus) vaginitis, preterm birth, contraception, multipurpose prevention technology strategies, cervicovaginal cancer, and general maintenance of vaginal health. Due to their excellent mechanical properties, electrospun scaffolds are also being investigated as next-generation materials in the surgical treatment of pelvic organ prolapse. In this article, we review the latest advances in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.121040DOI Listing
September 2021

Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations.

Int J Mol Sci 2021 Jul 28;22(15). Epub 2021 Jul 28.

School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

Microfluidic technique has emerged as a promising tool for the production of stable and monodispersed nanoparticles (NPs). In particular, this work focuses on liposome production by microfluidics and on factors involved in determining liposome characteristics. Traditional fabrication techniques for microfluidic devices suffer from several disadvantages, such as multistep processing and expensive facilities. Three-dimensional printing (3DP) has been revolutionary for microfluidic device production, boasting facile and low-cost fabrication. In this study, microfluidic devices with innovative micromixing patterns were developed using fused deposition modelling (FDM) and liquid crystal display (LCD) printers. To date, this work is the first to study liposome production using LCD-printed microfluidic devices. The current study deals with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes with cholesterol (2:1) prepared using commercial and 3D-printed microfluidic devices. We evaluated the effect of microfluidic parameters, chip manufacturing, material, and channel design on liposomal formulation by analysing the size, PDI, and ζ-potential. Curcumin exhibits potent anticancer activity and it has been reported that curcumin-loaded liposomes formulated by microfluidics show enhanced encapsulation efficiency when compared with other reported systems. In this work, curcumal liposomes were produced using the developed microfluidic devices and particle sizing, ζ-potential, encapsulation efficiency, and in vitro release studies were performed at 37 °C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22158064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348465PMC
July 2021

Thermally reactive N-(2-hydroxypropyl)methacrylamide (HPMA) amphiphiles for drug solubilisation.

Int J Pharm 2021 May 2;601:120570. Epub 2021 Apr 2.

School of Pharmacy and Bioengineering, Keele University, Keele ST5 5BG, UK; Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1RD, UK. Electronic address:

Thermally active polymers, can respond structurally to temperature changes, making them interesting as potential drug delivery vehicles. Polymers of N-(3-aminopropyl) methacrylamide hydrochloride (APMA) are cationic with primary amine groups in their structure, which have been explored in biomedical applications via post-polymerisation modifications. In this work, we synthesised amphiphilic APMA monomers using hydrophobic pendant groups via conjugation onto their primary amine group. The pendant groups chosen in this study were palmitoyl, dansyl and cholesteryl moieties. The amphiphilic monomers were subsequently copolymerized with N-(2-hydroxypropyl)methacrylamide (HPMA) using varied monomer feed ratios resulting in a thermo-responsive system. The ability of the resultant aggregates in aqueous solution to encapsulate and liberate model drugs (e.g., propofol, griseofulvin and prednisolone) was then determined. Our data showed that the HPMA based formulations were capable of loading the model drug molecules inside their lipophilic core; HPMA-co-(APMA-Dansyl 2%) exhibited the largest drug encapsulation ability. Subsequently, poly(ethylene glycol) (PEG) was incorporated into the intrinsic polymer structure. This resulted in a more rapid drug release profile, whereby 100% of griseofulvin and prednisolone were liberated after only 4 h, which was only 5% and 10% before the PEG inclusion, respectively. Similarly, propofol showed 70% liberation from the polymer aggregate after 24 h, compared with only 30% liberation pre-PEGylation. These studies give an insight into the potential of the HMPA based amphiphiles as thermally responsive cargo carrier/release systems which could be exploited in the delivery of poorly soluble drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120570DOI Listing
May 2021

3D scaffolds in the treatment of diabetic foot ulcers: New trends vs conventional approaches.

Int J Pharm 2021 Apr 27;599:120423. Epub 2021 Feb 27.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, affecting roughly 25% of diabetic patients and resulting in lower limb amputation in over 70% of known cases. In addition to the devastating physiological consequences of DFU and its impact on patient quality of life, DFU has significant clinical and economic implications. Various traditional therapies are implemented to effectively treat DFU. However, emerging technologies such as bioprinting and electrospinning, present an exciting opportunity to improve current treatment strategies through the development of 3D scaffolds, by overcoming the limitations of current wound healing strategies. This review provides a summary on (i) current prevention and treatment strategies available for DFU; (ii) methods of fabrication of 3D scaffolds relevant for this condition; (iii) suitable materials and commonly used molecules for the treatment of DFU; and (iv) future directions offered by emerging technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120423DOI Listing
April 2021

Fused deposition modelling for the development of drug loaded cardiovascular prosthesis.

Int J Pharm 2021 Feb 21;595:120243. Epub 2021 Jan 21.

School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK. Electronic address:

Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120243DOI Listing
February 2021

3D printed estradiol-eluting urogynecological mesh implants: Influence of material and mesh geometry on their mechanical properties.

Int J Pharm 2021 Jan 10;593:120145. Epub 2020 Dec 10.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

Current treatment for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) involves transvaginal implantation of surgical mesh, conventionally made of polypropylene (PP). However, it has recently become apparent that the mechanical properties of PP are unsuitable, resulting in serious complications such as tissue erosion. In this study, thermoplastic polyurethane (TPU) was chosen as an alternative material, and hormone-loaded meshes were produced by fused deposition modelling (FDM). Filaments containing various concentrations (0%, 0.25%, 1%) of 17-β-estradiol (E2) were prepared by hot-melt extrusion (HME) and were 3D printed into meshes with various geometries. The resulting meshes were characterised through a variety of instruments such as attenuated total reflection-Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), thermal analysis, fracture force and in vitro release studies. The results showed that E2 was homogeneously distributed throughout the TPU matrix. Moreover, the thermogravimetric analysis (TGA) showed degradation temperatures above those used during the FDM process, showing that the meshes can be produced below the degradation temperatures of the materials. The fracture force testing showed that material and mesh geometry influence mechanical properties, with TPU meshes appearing more elastic and therefore more suitable for pelvic floor repair than PP mesh. However, interestingly the mechanical properties of the TPU70 filament was not affected by the inclusion of E2. In addition, the 3D printed meshes showed a linear E2 release profile over a two weeks period, which can be modified according to the percentage of E2 added to the 3D printed construct. This proof of concept study demonstrates the potential of using FDM to create a new generation of safer mesh implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2020.120145DOI Listing
January 2021

Novel combination of non-invasive morphological and solid-state characterisation of drug-loaded core-shell electrospun fibres.

Int J Pharm 2020 Sep 31;587:119706. Epub 2020 Jul 31.

University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre utca 7-9, H-1092 Budapest, Hungary. Electronic address:

In recent years, core-shell nanofibrous drug delivery systems have received increasing attention due to their ability to incorporate two or more active pharmaceutical ingredients (APIs) individually into the desired layer (either core or sheath) and thereby finely tune the release profiles of even incompatible drugs in one system. This study aims to perform formulation and solid-state characterisation of levofloxacin-loaded polylactic acid (PLA) - naproxen-sodium-loaded polyvinyl pyrrolidone (PVP) bicomponent core-shell fibrous sheets and examine the electro spinnability of the precursor combinations. The selected drugs have potential therapeutic relevance in similar systems intended for wound healing; however, in this study, they are used as model drugs to understand the physicochemical properties of a drug loaded system. In order to determine the best core- and shell-solution combination, a full factorial experimental design is used. A combination of various morphological (scanning electron microscopy and transmission electron microscopy) and microstructural characterisation techniques (X-ray photoelectron spectroscopy and Raman spectroscopy) was applied to non-invasively obtain information about the structure of the fibres and the embedded drugs. The results indicate that core-shell fibres of different compositions could be successfully prepared with various structural homogeneities. The best core-shell structure was obtained using a combination of 15% (w/w) shell concentration and 8% (w/w) PLA solution concentration. In addition to the conventional core-shell structural verification methods, the Raman spectroscopy method was implemented to reveal not only the core-shell structure of the PLA/PVP nanofibers but also the form of the embedded drugs. The Raman mapping of the fibres confirm the above results, and it is shown that an amorphous solid dispersion is formed as a result of the coaxial electrospinning process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2020.119706DOI Listing
September 2020

Emerging technologies for diagnostics and drug delivery in the fight against COVID-19 and other pandemics.

Expert Rev Med Devices 2020 Oct 17;17(10):1007-1012. Epub 2020 Jul 17.

School of Pharmacy, Queen's University Belfast , Belfast, UK.

Introduction: A pandemic is the worst-case scenario in the field of infectious diseases. Innovative technologies have the potential to address the challenges associated with the manufacture of personalized drug delivery systems, biosensors, and medical devices during a pandemic. 3D-Printing, microfluidics, and Microelectromechanical systems (MEMS) can provide an important part on this fight, as are cheap, easy to be operated, capable to provide rapid detection and monitoring of a disease, and deliver medicines.

Areas Covered: This manuscript answers the question of how these emerging technologies can save lives during a pandemic by avoiding supply chain delays and also by providing rapid diagnostics, disease monitoring, or by offering personalized treatments. The manuscript covers recent approaches in the topic with a focus in manuscripts published in the last year and by emphasising recent regulatory considerations by regulatory agencies in the manufacturing of 3DP systems or other medical devices during COVID.

Expert Opinion: New manufacturing techniques are emerging with the ability to address the challenges associated with the development of medical devices or diagnostics, during a pandemic. Are many challenges in order to achieve this and especially in short times that are required under a pandemic attack, which will also be covered in this manuscript.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17434440.2020.1792287DOI Listing
October 2020

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs.

Mol Pharm 2020 09 3;17(9):3487-3500. Epub 2020 Aug 3.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, U.K.

Implantable devices are versatile and promising drug delivery systems, and their advantages are well established. Of these advantages, long-acting drug delivery is perhaps the most valuable. Hydrophilic compounds are particularly difficult to deliver for prolonged times. This work investigates the use of poly(caprolactone) (PCL)-based implant coatings as a novel strategy to prolong the delivery of hydrophilic compounds from implantable devices that have been prepared by additive manufacturing (AM). Hollow implants were prepared from poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) using fused filament fabrication (FFF) AM and subsequently coated in a PCL-based coating. Coatings were prepared by solution-casting mixtures of differing molecular weights of PCL and poly(ethylene glycol) (PEG). Increasing the proportion of low-molecular-weight PCL up to 60% in the formulations decreased the crystallinity by over 20%, melting temperature by over 4 °C, and water contact angle by over 40°, resulting in an increased degradation rate when compared to pure high-molecular-weight PCL. Addition of 30% PEG to the formulation increased the porosity of the formulation by over 50% when compared to an equivalent PCL-only formulation. These implants demonstrated release rates for hydrophilic model compounds (methylene blue and ibuprofen sodium) ranging from 0.01 to 34.09 mg/day, depending on the drug used. The versatility of the devices produced in this work and the range of release rates achievable show great potential. Implants could be specifically developed in order to match the specific release rate required for a number of drugs for a wide range of conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482401PMC
September 2020

Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies.

Pharmaceutics 2020 Jun 11;12(6). Epub 2020 Jun 11.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12060542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356280PMC
June 2020

Urogynecological surgical mesh implants: New trends in materials, manufacturing and therapeutic approaches.

Int J Pharm 2020 Jul 8;585:119512. Epub 2020 Jun 8.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI) are two prevalent disorders affecting 30-40% of women worldwide. Current strategies to repair or improve these medical conditions are non-surgical options such as physiotherapy, or surgical options such as the use of vaginal meshes. The synthetic material polypropylene (PP), which has long been used for manufacturing these vaginal meshes, is associated with severe complications such as chronic pain, infection or mesh erosion. As a result of a widespread reporting and unacceptably high rates of complications, these issues have become a public health concern. Regulatory bodies have recently deemed the transvaginal placement of PP mesh in the pelvic floor (PF) no longer a suitable treatment method for PF repair, leading to the need for a novel approach to the manufacture and selection of materials for urogynecological meshes. Medical devices, such as vaginal meshes can be manufactured using a variety of techniques including injection moulding, electrospinning, hot-melt extrusion (HME) or more recently 3D printing. Over the past decade, the use of 3D printing within the medical device industry has expanded and offers a promising approach to manufacture patient-specific surgical mesh when combined with imaging tools. This review will summarise the current strategies to treat POP and SUI, the issues and use of current meshes for the treatment of these pelvic floor disorders (PFDs), and the future directions for the manufacture of more suitable urogynecological meshes, as well as their potential materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2020.119512DOI Listing
July 2020

3D Printing of Pharmaceuticals and Drug Delivery Devices.

Pharmaceutics 2020 Mar 15;12(3). Epub 2020 Mar 15.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

The process of 3D printing (3DP) was patented in 1986; however, the research in the field of 3DP did not become popular until the last decade. There has been an increasing research into the areas of 3DP for medical applications for fabricating prosthetics, bioprinting and pharmaceutics. This novel method allows the manufacture of dosage forms on demand, with modifications in the geometry and size resulting in changes to the release and dosage behaviour of the product. 3DP will allow wider adoption of personalised medicine due to the diversity and simplicity to change the design and dosage of the products, allowing the devices to be designed specific to the individual with the ability to alternate the drugs added to the product. Personalisation also has the potential to decrease the common side effects associated with generic dosage forms. This Special Issue Editorial outlines the current innovative research surrounding the topic of 3DP, focusing on bioprinting and various types of 3DP on applications for drug delivery as well advantages and future directions in this field of research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12030266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150971PMC
March 2020

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing.

Pharmaceutics 2020 Jan 28;12(2). Epub 2020 Jan 28.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Implantable drug delivery devices offer many advantages over other routes of drug delivery. Most significantly, the delivery of lower doses of drug, thus, potentially reducing side-effects and improving patient compliance. Three dimensional (3D) printing is a flexible technique, which has been subject to increasing interest in the past few years, especially in the area of medical devices. The present work focussed on the use of 3D printing as a tool to manufacture implantable drug delivery devices to deliver a range of model compounds (methylene blue, ibuprofen sodium and ibuprofen acid) in two in vitro models. Five implant designs were produced, and the release rate varied, depending on the implant design and the drug properties. Additionally, a rate controlling membrane was produced, which further prolonged the release from the produced implants, signalling the potential use of these devices for chronic conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12020105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076405PMC
January 2020

3D Printing of Drug-Loaded Thermoplastic Polyurethane Meshes: A Potential Material for Soft Tissue Reinforcement in Vaginal Surgery.

Pharmaceutics 2020 Jan 13;12(1). Epub 2020 Jan 13.

School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.

Current strategies to treat pelvic organ prolapse (POP) or stress urinary incontinence (SUI), include the surgical implantation of vaginal meshes. Recently, there have been multiple reports of issues generated by these meshes conventionally made of poly(propylene). This material is not the ideal candidate, due to its mechanical properties leading to complications such as chronic pain and infection. In the present manuscript, we propose the use of an alternative material, thermoplastic polyurethane (TPU), loaded with an antibiotic in combination with fused deposition modelling (FDM) to prepare safer vaginal meshes. For this purpose, TPU filaments containing levofloxacin (LFX) in various concentrations (e.g., 0.25%, 0.5%, and 1%) were produced by extrusion. These filaments were used to 3D print vaginal meshes. The printed meshes were fully characterized through different tests/analyses such as fracture force studies, attenuated total reflection-Fourier transform infrared, thermal analysis, scanning electron microscopy, X-ray microcomputed tomography (μCT), release studies and microbiology testing. The results showed that LFX was uniformly distributed within the TPU matrix, regardless the concentration loaded. The mechanical properties showed that poly(propylene) (PP) is a tougher material with a lower elasticity than TPU, which seemed to be a more suitable material due to its elasticity. In addition, the printed meshes showed a significant bacteriostatic activity on both and cultures, minimising the risk of infection after implanting them. Therefore, the incorporation of LFX to the TPU matrix can be used to prepare anti-infective vaginal meshes with enhanced mechanical properties compared with current PP vaginal meshes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023419PMC
January 2020

Recent Development of Electrospinning for Drug Delivery.

Pharmaceutics 2019 Dec 19;12(1). Epub 2019 Dec 19.

University Pharmacy Department of Pharmacy Administration, Semmelweis University, 7-9 Hőgyes Street, H-1092 Budapest, Hungary.

Electrospinning is one of the most widely used techniques for the fabrication of nano/microparticles and nano/microfibers, induced by a high voltage applied to the drug-loaded solution [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022792PMC
December 2019
-->