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Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

It is estimated that nearly a half of the world's population over 30 years old suffer from some kind of periodontal disease (PD). Although preventable, PD can pose a significant health burden to patients, causing from pain and discomfort to disfigurement and death. The management of PD often requires surgical procedures accompanied of systemic antibiotic and anti-inflammatory treatments. Curcumin (CUR), a potent anti-inflammatory and antimicrobial active, has shown great promise in the management of PD; however, its effects are often limited by its low bioavailability. In this work, we report the development of electrospun nanofibres (NFs) loaded with CUR nanocrystals (NCs) for the management of PD. NCs of 100 nm were obtained by media milling and loaded into dissolving polyvinyl alcohol NFs using electrospinning. The resultant NCs-in-NFs dissolved in water spontaneously, releasing NCs with a particle size of ∼120 nm. The physiochemical characterisation of the systems indicated the absence of chemical interactions between drug and polymer, and nanofibres with an amorphous nature. In vitro release profiles demonstrated that the NCs had a significantly higher dissolution rate (∼100 % at day 40) than the control group (approximately 6 % at day 40), which consisted of NFs containing a physical mixture of the drug and stabiliser. Finally, mucosal deposition studies demonstrated a 10-fold higher capacity of the novel NCs-in-NFs system to deposit CUR ex vivo using excised neonatal porcine mucosal tissue, when compared to the control group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture were greater than 10⁵ cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 10⁴ microorganisms penetrated into the viable tissue and 10⁶ cfu of Candida albicans and Staphylococcus epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Swelling kinetics, ionic conductivity and electrically assisted solute permeation (theophylline, methylene blue and fluorescein sodium) of poly(ethylene glycol) (PEG) crosslinked poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) hydrogels are presented. The effects of PMVE/MA concentration and PEG molecular weight (MW) on swelling behaviour and network parameters were investigated in phosphate buffered saline (pH 7.4). The percentage swelling of hydrogels increased, and the crosslink density decreased, with a decrease in PMVE/MA content and with an increase in PEG MW. The ionic conductivity of the formulation was found to increase with an increase in PEG MW. The application of an electrical current led to a significant enhancement in the rate and extent of solute permeation across the swollen hydrogels. Furthermore, it was found that the extent of solute permeation enhancement following current application was dependent upon the crosslink density and ionic conductivity of the formulation. In general, a decrease in crosslink density and an increase in ionic conductivity led to a greater enhancement in solute permeation following current application. The electro-responsive nature of these hydrogels suggests that have a potential application in electrically controlled drug delivery systems., (Copyright © 2011 Elsevier B.V. All rights reserved.)