Posaconazole-hemp seed oil loaded nanomicelles for invasive fungal disease.

Invasive fungal infections (IFI) pose a significant health burden, leading to high morbidity, mortality, and treatment costs. This study aims to develop and characterize nanomicelles for the codelivery of posaconazole and hemp seed oil for IFI via the oral route. The nanomicelles were prepared using a nanoprecipitation method and optimized through the Box Behnken design. The optimized nanomicelles resulted in satisfactory results for zeta potential, size, PDI, entrapment efficiency, TEM, and stability studies. FTIR and DSC results confirm the compatibility and amorphous state of the prepared nanomicelles. Confocal laser scanning microscopy showed that the optimized nanomicelles penetrated the tissue more deeply (44.9µm) than the suspension (25µm). The drug-loaded nanomicelles exhibited sustained cumulative drug release of 95.48 ± 3.27% for 24 h. The nanomicelles showed significant inhibition against Aspergillus niger and Candida albicans (22.4 ± 0.21 and 32.2 ± 0.46 mm, respectively). The pharmacokinetic study on Wistar rats exhibited a 1.8-fold increase in relative bioavailability for the nanomicelles compared to the suspension. These results confirm their therapeutic efficacy and lay the groundwork for future research and clinical applications, providing a promising synergistic antifungal nanomicelles approach for treating IFIs.

Hypothesizing the Oleic Acid-Mediated Enhanced and Sustained Transdermal Codelivery of Pregabalin and Diclofenac Adhesive Nanogel: A Proof of Concept.

Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120°, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.

Simultaneous Determination of Posaconazole and Hemp Seed Oil in Nanomicelles through RP-HPLC via a Quality-by-Design Approach.

The present study involves the development of a reverse-phase HPLC method employing the quality-by-design methodology for the estimation of posaconazole and hemp seed oil simultaneously in nanomicelles formulation. The successful separation of posaconazole and hemp seed oil was achieved together, and this is the first study to develop and quantify posaconazole and hemp seed oil nanomicelles with linoleic acid as the internal standard and developed a dual drug analytical method employing a quality-by-design approach. The study was performed on a Shimadzu Prominence-I LC-2030C 3D Plus HPLC system with a PDA detector and the Shim-pack Solar C8 column (250 mm × 4.6 mm × 5 µm) for analysis with a mobile phase ratio of methanol:water (80:20% v/v) maintaining the flow rate of 1.0 mL/min. The final wavelength was selected as 240 nm and the elution of hemp seed oil and posaconazole was obtained at 2.7 and 4.6 min, respectively, with a maximum run time of 8.0 min. Box Behnken design was employed to optimize the method, keeping the retention time, peak area, and theoretical plates as dependent variables, while the mobile phase composition, flow rate, and wavelengths were chosen as independent variables. Parameters such as specificity, accuracy, robustness, linearity, sensitivity, precision, ruggedness, and forced degradation study were performed to validate the method. The calibration curves of posaconazole and hemp seed oil were determined to be linear throughout the range for concentration. The suggested approach can be effectively utilized for estimating the content of drugs from their nanoformulation and proved suitable for both in vivo and in vitro research.

Decoding the bidirectional relationship between gut microbiota and COVID-19.

From late 2019, whole world has been facing COVID-19 pandemic which is caused by SARS-CoV-2 virus. This virus primarily attacks the respiratory tract and enter host cell by binding with angiotensin 2 converting enzyme receptors present on alveoli of the lungs. Despite its binding in the lungs, many patients have reported gastrointestinal symptoms and indeed, RNA of the virus have been found in faecal sample of patients. This observation gave a clue of the involvement of gut-lung axis in this disease development and progression. From several studies reported in past two years, intestinal microbiome has shown to have bidirectional link with lungs i.e., gut dysbiosis increases the tendency of infection with COVID-19 and coronavirus can also cause perturbations in intestinal microbial composition. Thus, in this review we have tried to figure out the mechanisms by which disturbances in the gut composition can increase the susceptibility to COVID-19. Understanding these mechanisms can play a crucial role in decreasing the disease outcomes by manipulating the gut microbiome using prebiotics, probiotics, or combination of two. Even, faecal microbiota transplantation can also show better results, but intensive clinical trials need to be done first.