ABSTRACT
PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. It is characterized by irregular menstrual cycles, hyperandrogenism, and polycystic ovaries. The syndrome's etiology is multifactorial, involving genetic, hormonal, metabolic, and environmental factors. Given its diverse effects, managing PCOS requires a comprehensive approach. METHODS: This study employed a Sprague-Dawley rat model to investigate the effects of ellagic acid on polycystic ovary syndrome (PCOS). Forty adult female rats were randomly divided into four groups: a control group, a healthy group receiving ellagic acid (200 mg/kg), a PCOS group, and an ellagic acid + PCOS group. PCOS was induced in the relevant groups through subcutaneous injection of estradiol valerate (2 mg/kg), and ellagic acid was administered via subcutaneous injections for 14 days. Blood samples were collected for hormone analysis using the ELISA method, and ovarian tissues were processed for histological examination. RESULT: Ellagic acid treatment showed reduced LH levels and restoration of follicular development, particularly primordial and graafian follicles, along with modulation of miRNA-21 expression. Moreover, ellagic acid exhibited positive effects on ovarian morphology, including decreased theca layer thickness, increased oocyte diameter, and improvements in antral and preovulatory follicles. This suggests ellagic acid's potential in addressing follicular development and oocyte quality in PCOS. CONCLUSIONS: These findings suggest ellagic acid as a potential complementary approach in PCOS management. While the study is promising, further research, including clinical trials, is required to elucidate ellagic acid's mechanisms and clinical efficacy in human PCOS subjects.
ABSTRACT
Transdermal drug delivery systems offer several advantages over conventional oral or hypodermic administration due to the avoidance of first-pass drug metabolism and gastrointestinal degradation as well as patients' convenience due to a minimally invasive and painless approach. A novel transdermal drug delivery system, comprising a combination of transfersomes with either solid silicon or solid polycarbonate microneedles has been developed for the transdermal delivery of aspirin. Aspirin was encapsulated inside transfersomes using a "thin-film hydration sonication" technique, yielding an encapsulation efficiency of approximately 67.5%. The fabricated transfersomes have been optimised and fully characterised in terms of average size distribution and uniformity, surface charge and stability (shelf-life). Transdermal delivery, enhanced by microneedle penetration, allows the superior permeation of transfersomes into perforated porcine skin and has been extensively characterised using optical coherence tomography (OCT) and transmission electron microscopy (TEM). In vitro permeation studies revealed that transfersomes enhanced the permeability of aspirin by more than four times in comparison to the delivery of unencapsulated "free" aspirin. The microneedle-assisted delivery of transfersomes encapsulating aspirin yielded 13-fold and 10-fold increases in permeation using silicon and polycarbonate microneedles, respectively, in comparison with delivery using only transfersomes. The cytotoxicity of different dose regimens of transfersomes encapsulating aspirin showed that encapsulated aspirin became cytotoxic at concentrations of ≥100 µg/mL. The results presented demonstrate that the transfersomes could resolve the solubility issues of low-water-soluble drugs and enable their slow and controlled release. Microneedles enhance the delivery of transfersomes into deeper skin layers, providing a very effective system for the systemic delivery of drugs. This combined drug delivery system can potentially be utilised for numerous drug treatments.
ABSTRACT
Polymer-based solid microstructures (MSts) have the potential to significantly increase the quantity and range of drugs that can be administered across the skin. MSt arrays are used to demonstrate their capacity to bypass the skin barrier and enhance permeability by creating microchannels through the stratum corneum, in a minimally invasive manner. This study is designed to demonstrate the ability of MSts to exceed the current boundaries for transdermal delivery of compounds with different molecular weights, partition coefficients, acid dissociation constants, melting points, and water solubilities. In vitro permeation of a range of selected molecules, including acetyl salicylic acid (aspirin), galantamine, selegiline hydrochloride (Sel-HCl), insulin, caffeine, hydrocortisone (HC), hydrocortisone 21-hemisuccinate sodium salt (HC-HS) and bovine serum albumin (BSA) has been studied across excised porcine skin with and without poke and patch application of MSts. Permeation of the molecules was monitored using Franz diffusion cells over 24 h. MSts significantly increased the permeation of all selected molecules up to 40 times, compared to topical applications of the molecules without MSts. The greatest increase in permeation was observed for caffeine with 70 ± 8% permeation and the lowest enhancement was observed for HC with a 2.4 ± 1.3% increase in permeation. The highest obtained flux was BSA (8133 ± 1365 µg/cm2/h) and the lowest flux observed for HC (11 ± 4 µg/cm2/h). BSA and HC also showed the highest (16,275 ± 3078 µg) and the lowest (73 ± 47 µg) permeation amount after 24 h respectively. MSt-treated skin exhibits greatly increased permeation. The molecule parameters (size, acid dissociation constant, partition coefficient and solubility)-traditional hurdles associated with passive diffusion through intact skin-are overcome using MSt skin treatment.
