Raisuddin Ali

Objective: We developed delafloxacin (Dela)-loaded PLGA nanoparticles (PNPs) for potential ocular application via a topical route to treat eye infections caused by Gram-positive and Gram-negative bacteria. Methodology: Dela-PNPs were formulated using the emulsification-solvent evaporation method and stabilized using poly(vinyl alcohol) (PVA). Size and morphology were characterized by using dynamic light scattering (DLS) and scanning electron microscopy (SEM). Drug loading and encapsulation efficiency were measured via HPLC. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) assessed the physical state and drug-polymer interaction. The in vitro drug release was evaluated using the dialysis bag method in simulated tear fluid (STF, pH 7.4) with Tween 80 (0.5%). The antimicrobial efficacy was determined by a minimum inhibitory concentration (MIC) and zone of inhibition tests against various bacteria. Results: Optimally sized PNPs were produced (238.9 +/- 10.2 nm) with a PDI of 0.258 +/- 0.084 and a zeta-potential of 2.78 +/- 0.34 mV. Using 40 mg of PLGA, 4 mg of Dela, and 1% PVA, drug encapsulation and loading were 84.6 +/- 7.3 and 12.9 +/- 1.7%, respectively. DSC indicated that Dela was entrapped in an amorphous state within the PNPs. FTIR spectra showed no drug-polymer interactions. The formulation showed 40.6 +/- 4.2% drug release within 24 h and 84.4 +/- 6.1% by 96 h. MIC tests showed high susceptibility of Streptococcus pneumoniae, Klebsiella pneumoniae, and Escherichia coli (similar to 0.31 mu g/mL) compared to Staphylococcus aureus and MRSA-6538 (similar to 0.63 mu g/mL) and Bacillus subtilis (2.5 mu g/mL). Stability studies showed minimal changes in particle characteristics over 3- and 6-month storage at 25 and 37 degrees C. Conclusion: Dela-PNPs exhibit significant potential as a nanoformulation for ocular applications.

Background/Objectives: Burn lesions damage the skin's outermost defensive layer, allowing pathogenic microbes including Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli to infiltrate. Silver sulfadiazine (SSD) is an effective antibacterial agent approved by U.S. Food and Drug Administration (US-FDA) and is considered as the gold standard for burn wound treatment. Despite the high degree of efficacy of SSD in burn wound management, it possesses some drawbacks, such as poor solubility, low topical bioavailability and skin irritations. The present study endeavours to develop nanosuspension based SSD nanogel for improving the deliverability of SSD and its therapeutic outcomes for the management of partial thickness burn; Methods: The SSD nanosuspension was formulated employing controlled nanoprecipitation approach using various surfactants; Results: The formulation was optimized utilizing one-factor-at-a-time approach and to fetch the optimized formulation of 134.6 nm size. The optimized nanosuspension was incorporated into chitosan gel that offer superior drug release potential, and also offered better spreadability (5.21 ± 0.38g) and extrudability (152.27 ± 0.22 gm) that represents the easy application over the skin and extrusion of gel from the tube; Conclusions: The formulation was well tolerated as shown by skin irritation study and offered a superior burn lesion healing characteristics vis-à-vis the marketed product, even at a lower concentration. Hence, the formulation offers a huge potential in enhancing the clinical outcomes of SSD, especially in the management of partial thickness burn. The developed system with the above mentioned outcomes could be a promising delivery system for partial thickness burn wound management.

Lung cancer is a major public health concern, with a high incidence and fatality rate. Its treatment is very difficult, as it is mostly diagnosed in advanced stages. Non-small cell lung carcinoma (NSCLC) is the major form of lung carcinoma that persists. Brigatinib (BGT), a powerful small-molecule tyrosine kinase inhibitor, has demonstrated significant therapeutic potential in the treatment of NSCLC with anaplastic lymphoma kinase (ALK) mutations. However, the therapeutic applicability of BGT is hampered by its low solubility and bioavailability. In this study, we developed a mixed micelle system comprising Soluplus and TPGS loaded with BGT. BGT was encapsulated into the mixed micelles using various combinations of Soluplus and TPGS, with encapsulation efficiency (EE%) ranging from 52.43 ± 1.07 to 97.88 ± 2.25%. The dynamic light scattering data showed that the mixed micelles ranged in size from 75.7 ± 0.46 to 204.3 ± 5.40 nm. The selected mixed micelles (F6) showed approximately 38% BGT release in the first 2 h, and subsequently, within 72 h, the release was 94.50 ± 5.90%. The NMR experiment confirmed the formation of micelles. Additionally, the mixed micelles showed significantly higher cellular uptake (p < 0.05) and increased cytotoxicity (p < 0.05) as compared to the free BGT. Specifically, the obtained IC₅₀ values for BGT-loaded Soluplus-TPGS mixed micelles and free BGT were 22.59 ± 6.07 and 61.45 ± 6.35 μg/mL, respectively. The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.