Rania M. Yehia

Microneedles (MNs) offer a promising alternative for transdermal delivery of hydrophilic drugs such as sitagliptin, evading the gastrointestinal side effects associated with oral administration. Thus, the study focuses on the transdermal delivery of sitagliptin, an antidiabetic drug that inhibits dipeptidyl peptidase-4 (DPP-4). The research includes the formulation and in-vitro, ex-vivo, and in-vivo characterization of MNs for sitagliptin delivery. MN molds were fabricated using Stereolithography (3D Printing), and biocompatible MNs were made from hyaluronic acid (HA), chitosan, polyvinylpyrrolidone and polyvinyl alcohol (PVA). Sitagliptin MNs with PVA (SMP) and HA (SMH) exhibited favorable physical and mechanical properties, with drug content of 3.5 ± 0.14 mg/g and 3.8 ± 0.12 mg/g, respectively. SMH showed superior skin penetration due to sharper, stiffer tips. Ex-vivo studies using rat skin indicated that the SMH yielded a higher cumulative permeation (36.58%) compared to SMP (24.04%). Additionally, sitagliptin primarily accumulated in the epidermis, with approximately 56% for SMH and 50% for SMP. In-vivo results demonstrated that both SMP and SMH effectively lowered fasting blood glucose levels, with SMH notably improving postprandial glucose and insulin levels. Overall, HA-based biodegradable microneedles present a promising, minimally invasive strategy for sitagliptin delivery, enabling effective type 2 diabetes management while avoiding its gastrointestinal side effects.

Individuals experiencing hair loss, irrespective of gender, confront significant psychological challenges. This study explores the untapped potential of rosemary oil (ROS) to stimulate hair growth, addressing its limited permeability. The focus is on innovating ROS-loaded microsponges (MS) for enhanced topical application. Utilizing Box-Behnken design (3³), the study optimizes ROS-MS compositions by varying solvent volume, polymer mix, and drug concentration. The optimized ROS-MS formulation exhibits noteworthy attributes: a 94% ± 0.04 production yield, 99.6% ± 0.5 encapsulation efficiency, and 96.4% ± 1.6 cumulative ROS release within 24 h. These microsponges exhibit uniformity with a particle size of 14.1 µm ± 4.5. The OPT-ROSMS-gel showcases favorable characteristics in appearance, spreadability, pH, drug content, and extrudability. Ex-vivo skin deposition tests highlight heightened permeability of OPT-ROSMS-gel compared to pure ROS-gel, resulting in three-fold increased follicular retention. In-vivo studies underscore the superior efficacy of OPT-ROSMS-gel, revealing enhanced hair development in length, thickness, and bulb diameter, surpassing ROS-gel and minoxidil by approximately 1.2 and 1.5 times, respectively, along with nearly two-fold increase in β-catenin levels. In conclusion, microsponges emerge as a promising ROS delivery method, effectively addressing hair loss. This research advances hair loss treatments and underscores the significance of this innovative paradigm in fostering hair growth.

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box–Behnken design 3³. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.

Purpose: The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug. Methods: Data modelling was implemented using Plackett-Burman design to identify the main variables affecting the formulation of ADA-MS. The adopted method of preparation for MS was quasi-emulsion solvent diffusion method. The nominated independent variables were volume of organic phase, sonication time, stirring speed, drug percent, polymer type, emulsifier concentration, and method of organic phase addition. As for the dependent variables, they included entrapment efficiency (E.E.%), production yield (P.Y.%), particle size (P.S.) and morphology. Furthermore, selected ADA loaded microsponges (ADA-MS) were in vitro assayed for their biological activities via cytotoxicity, UVA irradiation and cell viability, and antimicrobial activity. Results: The study indicated that the drug percent, polymer type and surfactant concentration have the key significant effect on E.E.% and P.Y.%, while, the drug percent, stirring speed and volume of organic phase have had a significant effect on P.S. and their morphology. Furthermore, ADA-MS had a momentous cytotoxic effect on A431 and M10 cell-lines with exceptional enrichment when the polymer Eudragit RS100 was used. Also, the ADA-MS increased the cell viability after UVA irradiation on HFB-4 cell-line by 14% to 43%, especially when using Ethyl Cellulose as a polymer. Lastly, the antimicrobial activity of ADA against Propionibacterium acnes was boosted when incorporated into MS. Conclusion: The Plackett−Burman design proved its impact in discerning preparation variables affecting the quality of ADA-MS formulation, with heightening of the in vitro biological activities of ADA. Thus, MS was presumed to be an auspicious carrier system for ADA. Graphical Abstract:

Microemulsion (ME) systems are now considered of the most successful transdermal drug delivery systems. This is due to their nanodroplets size in the one hand and to their composition that enables the use of several mechanistically penetration enhancers in the same formulation on the other hand. This work summarizes the types, properties, and the merits of the use of MEs for transdermal delivery and reviews the successful studies that were performed to deliver several drugs through this important route during the past 10–12 years.