Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: In Vivo Study in a Fungal Keratitis Model.

Fungal keratitis (FK) is a fungal infection of the cornea, which is part of the eye and causes corneal ulcers and an increased risk of permanent blindness, which is often found in Candida albicans species. Amphotericin B (AMB), which is a group of polyenes as the first-line treatment of FK, is effective in annihilating C. albicans. However, AMB preparations such as eye drops and ointments have major drawbacks, for instance, requiring more frequent administrations, loss of the drug by the drainage process, and rapid elimination in the precornea, which result in low bioavailability of the drug. An ocular dissolving microneedle containing the solid dispersion amphotericin B (DMN-SD-AMB) had been developed using a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers, while the solid dispersion AMB (SD-AMB) was contained in the needle as a drug. This study aims to determine the most optimal and safest DMN-SD-AMB formula for the treatment of FK in the eye as well as a solution to overcome the low bioavailability of AMB eye drops and ointment preparations. SD-AMB had been successfully developed, which was characterized by increased antifungal activity and drug release in vitro compared to other treatments. Furthermore, DMN-SD-AMB studies had also been successfully performed with the best formulation, which exhibited the best ex vivo corneal permeation profile and antifungal activity as well as being safe from eye irritation. In addition, an in vivo antifungal activity using a rabbit infection model shows that the number of fungal colonies was 0.98 ± 0.11 log10 CFU/mL (F3), 5.76 ± 0.32 log10 CFU/mL (AMB eye drops), 4.01 ± 0.28 log10 CFU/mL (AMB ointments), and 9.09 ± 0.65 log10 CFU/mL (control), which differed significantly (p < 0.05). All of these results evidence that DMN-SD-AMB is a new approach to developing intraocular preparations for the treatment of FK.

Enhancement of skin localization of ß-carotene from red fruit (Pandanus conoideus Lam.) using solid dispersion-thermoresponsive gel delivered via polymeric solid microneedles.

Red fruit (Pandanus conoideus Lam.) boasts high ß-carotene (BC) content, often consumed orally. However, absorption issues and low bioavailability due to food matrix interaction have led to transdermal delivery exploration. Nevertheless, BC has a short skin retention time. To address these limitations, this study formulates a ß-carotene solid dispersion (SD-BC) loaded thermoresponsive gel combined with polymeric solid microneedles (PSM) to enhance in vivo skin bioavailability. Characterization of SD-BC includes saturation solubility, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in vitro release. Characterization of SD-BC thermoresponsive gel includes gelation temperature, viscosity, rheological behaviour, pH, bio-adhesiveness, spreadability, and extrudability. PSM's mechanical properties and insertion capability were assessed. Ex vivo and in vivo dermato-pharmacokinetic studies, drug content, hemolysis, and skin irritation assessments were conducted to evaluate overall performance. Results confirm amorphous SD-BC formation, enhancing solubility. Both SD-BC thermoresponsive gel and PSM exhibit favourable characteristics, including rheological properties and mechanical strength. In vitro release studies showed a seven-fold increase in BC release compared to plain hydrogel. SD-BC thermoresponsive gel combined with PSM achieves superior ex vivo permeation (Cmax = 305.43 ± 32.07 µg.mL-1) and enhances in vivo dermato-pharmacokinetic parameters by 200-400 %. Drug content, hemolysis, and skin irritation studies confirmed its safety and non-toxicity.

Hydrogel forming microneedle-mediated transdermal delivery of sildenafil citrate from polyethylene glycol reservoir: An ex vivo proof of concept study.

Erectile dysfunction (ED) is a disorder that often occurs in men worldwide. One of the drugs used as the first-line therapy for erectile dysfunction is sildenafil citrate (SC). Unfortunately, SC was commonly found in oral, injection, and transdermal dosage forms with some limitations, mainly related to low oral bioavailability caused by the occurrence of first-pass metabolism in the liver, and poor patient comfort and compliance. Therefore, it was essential to develop dosage forms to overcome these limitations. We developed hydrogel-forming microneedles (HFM) that can facilitate transdermal delivery of SC by penetrating the stratum corneum. HFM was made using polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) as polymers and several variations of tartaric acid as crosslinking agents. The evaluation of swelling properties, mechanical resistance, and penetration ability showed that the HFM produced had good insertion properties and swelling capabilities ranging from 300% to 700%. This HFM was designed to be integrated with a polyethylene glycol (PEG) reservoir prepared using several types of PEG with different molecular weights. The ex vivo permeation study showed that up to 80% of SC (equivalent to 20.2 ± 0.29 mg/mL) was delivered transdermally from this combined dosage form. For the first time, SC has been successfully developed into an HFM that was integrated with a PEG reservoir which was non-irritating, safe, and painless. It also had promising results for increasing the effectiveness of ED therapy.