Publications by authors named "Essyrose Mathew"

12 Publications

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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.
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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.
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http://dx.doi.org/10.1007/s13346-022-01115-8DOI 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.
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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.
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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.
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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.
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http://dx.doi.org/10.1007/s13346-021-01078-2DOI Listing
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.
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http://dx.doi.org/10.1093/jpp/rgab136DOI 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.
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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.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120570DOI Listing
May 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.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120145DOI Listing
January 2021

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

Fused Deposition Modeling as an Effective Tool for Anti-Infective Dialysis Catheter Fabrication.

ACS Biomater Sci Eng 2019 Nov 7;5(11):6300-6310. Epub 2019 Oct 7.

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

Catheter-associated infections are a common complication that occurs in dialysis patients. Current strategies to prevent infection include catheter coatings containing heparin, pyrogallol, or silver nanoparticles, which all have an increased risk of causing resistance in bacteria. Therefore, a novel approach for manufacture, such as the use of additive manufacturing (AM), also known as three-dimensional (3D) printing, is required. Filaments were produced by extrusion using thermoplastic polyurethane (TPU) and tetracycline hydrochloride (TC) in various concentrations (e.g., 0, 0.25, 0.5, and 1%). The extruded filaments were used in a fused deposition modeling (FDM) 3D printer to print catheter constructs at varying concentrations. Release studies in phosphate-buffered saline, microbiology studies, thermal analysis, contact angle, attenuated total reflection-Fourier transform infrared, scanning electron microscopy, and X-ray microcomputer tomography (μCT) analysis were conducted on the printed catheters. The results suggested that TC was uniformly distributed within the TPU matrix. The microbiology testing of the catheters showed that devices containing TC had an inhibitory effect on the growth of NCTC 10788 bacteria. Catheters containing 1% TC maintained inhibitory effect after 10 day release studies. After an initial burst release in the first 24 h, there was a steady release of TC in all concentrations of catheters. 3D-printed antibiotic catheters were successfully printed with inhibitory effect on bacteria. Finally, TC containing catheters showed resistance to adherence to their surfaces when compared with catheters containing no TC. Catheters containing 1% of TC showed a bacterial adherence reduction of up to 99.97%. Accordingly, the incorporation of TC to TPU materials can be effectively used to prepare anti-infective catheters using FDM. This study highlights the potential for drug-impregnated medical devices to be created through AM.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01185DOI Listing
November 2019
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