Subconjunctival Delivery of Sorafenib-Tosylate-Loaded Cubosomes for Facilitated Diabetic Retinopathy Treatment: Formulation Development, Evaluation, Pharmacokinetic and Pharmacodynamic (PKPD) Studies.

Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.

Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal candidiasis.

The aim of the present investigation was to prepare and evaluate novel bioadhesive vaginal tablets containing clotrimazole loaded microspheres in order to provide long-term therapeutic activity at the site of infection. Tablets were prepared by incorporating drug loaded microspheres and using bioadhesive polymers hydroxypropylmethylcellulose, sodium carboxymethylcellulose and Carbopol. Microspheres were prepared by the spray drying technique using Eudragit RS-100 and Eudragit RL-100. Microspheres were characterized by SEM, DSC, FTIR, particle size analysis and evaluated for percentage yield, drug loading, encapsulation efficiency and in vitro drug release. To achieve bioadhesion to the mucosal tissue, optimized microspheres were incorporated into bioadhesive tablets and were evaluated for in vitro drug release, in vitro and in vivo mucoadhesion. FTIR and DSC studies showed that no chemical interaction occurred between the drug and polymers. The sphericity factor indicated that the prepared microspheres were spherical. Formulation Mt6 indicated a controlled in vitro drug release and good bioadhesive strength. The in vivo images confirmed the bioadhesion and retention property of tablets up to 24 h. The results indicated that this drug delivery system can be explored for controlled intravaginal drug release.