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The aim of the investigation was to develop nanoemulsion (NE) based emulgel of Mentha essential oil (MEO: potent antifungal property) to ensure enriched and extended therapeutic effectiveness against various species of Candidaand vaginal candidiasis. NE was prepared and optimized using central composite design. pH-triggered crosslinking of NE in carbopol 940 matrix (emulgel) was achieved by triethanolamine. Emulgel was evaluated for in vitro(against Candidaspp.) and in vivo(efficacy in Swiss albino female mice infected by installing 4 × 107 cfu/ml of Candida albicans) activity against the standard control and simple gel of MEO. NE droplets were observed to be spherical and uniform in size (178.087 ± 0.834 nm). Zeta potential and polydispersibility index (PDI) were measured using a diffraction light scattering technique and was found to be 31.56 ± 1.987 mV and 0.176, respectively. Emulgel demonstrated a significantly broader zone of growth inhibition than simple gel (gel of coarse emulsion) when studied against Candidaspp. In vivocolony counts of C. albicansin the case of emulgel were observed to be significantly lesser in number (165 cfu/ml) than simple gel (380 cfu/ml). Texture and viscosity of emulgel were measured using a texture analyser and Brookfield viscometer, respectively and were found to be reasonably acceptable for mucosal administration. Texture parameters of emulgel were consistent over 90 days (prolonged stability). Encapsulation of MEO in NE followed by crosslinking in cellulosic polymer ensures reduced volatility and improved effectiveness against candidiasis like condition.

Cyclosporine (CsA) delivery causes liver and kidney toxicities in long-term oral use, and its injections are inconvenient for frequent administration in psoriatic patients. Therefore, we aimed to develop polyvinyl alcohol (PVA) microneedle (MNs) arrays for poke and release of cyclosporine transcutaneously for systemic effect against psoriasis-like inflammation. Microneedles were fabricated using the micro-molding-cum-solvent casting method, characterized for patch dimensions and strength. Prepared MNs evaluated for drug loading, in vitrorelease, skin permeation studies, and in vivoanti-psoriatic activity. MNs showed the desired mechanical strength and dimensions with 6.8 ± 0.29 mg drug coated on needles surface per patch. MNs showed slow moisture gain in humid conditions with good skin penetration strength (up to 630 μm). More than a 60% reduction in the needle length was observed within 30 min of skin insertion. MNs showed fast (87% in 60 min) drug release and efficient permeation through the skin layer 60 min post-insertion into porcine skin. The developed MNs showed a significant reduction in PASI scoring and pro-inflammatory cytokines levels and a remarkable reduction in the spleen size. It was found stable for 6 months in accelerated conditions. In conclusion, the developed MNs array could be an excellent alternative to the existing dosage forms that can deliver cyclosporine transdermally to the systemic circulation to treat psoriasis-like inflammation in long-term use.

Tacrolimus ointment (Tac-Oint) treats mild, moderate, and severe psoriasiforms. However, thickened (inefficient penetration), dehydrated, and lipid deficient skin (low retention) limit its utility in severe psoriasiform. The microneedling process improves skin penetration, and nanostructured lipidic carrier (NLC) improves water and lipid level in the skin and its drug retention ability. Therefore, we developed Tac-NLC-Gel using Quality-by-Design-approach and compared its efficacy, with Tac-Oint-MN, against the Imiquimod-induced severe psoriasiform mice model. Spherical shape, negative charged NLC with diameter between 120 to 180 nm was transformed into Tac-NLC-Gel that possessed 5.3 ± 0.41 pH, 3200.89 ± 279.85 mPa viscosity, and excellent texture properties. Tac-NLC-Gel, due to hydrous polymer network and liquid lipid in NLC core, showed slow-release (52%), low permeation flux (3.12 ± 0.38 μgcm−2h−1), and high drug retention (67%) as compared to Tac-Oint in 24 h with 33% skin hydration in 8 days. However, microneedling resulted in low skin hydration, low retention, and 604 folds higher permeation due to increased porosity. Unlike Tac-Oint (followed paracellular diffusion), the distribution pattern of Tac-Oint-MN showed trans- and paracellular and Tac-NLC-Gel portrayed formation of carrier micro-conduits after trans-appendageal accumulation and transcellular diffusion. Tac-Oint-MN and Tac-NLC-Gel alleviated splenomegaly, Psoriasis area, severity index scores, and cytokine levels with improved macroscopic and behavioral conditions compared to those with the disease control group. Stability study supports the storage of the developed gel at 2–8 °C. In conclusion, both Tac-NLC-Gel and Tac-Oint-MN technologies have shown competitive relevance in treating severe psoriasiform; however, we recommend using Tac-NLC-Gel over Tac-Oint-MN in the hypothesized condition. The NLC-Gel benefits drug penetration and localization by improving skin hydration; however, Oint-MN provides faster skin penetration.