Buspirone Hydrochloride Loaded In Situ Nanovesicular Gel as an Anxiolytic Nasal Drug Delivery System: In Vitro and Animal Studies.

Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).

Local administration of irinotecan using an implantable drug delivery device stops high-grade glioma tumor recurrence in a glioblastoma tumor model.

The treatment for Glioblastoma is limited due to the presence of the blood brain barrier, which restricts the entry of chemotherapeutic drugs into the brain. Local delivery into the tumor resection margin has the potential to improve efficacy of chemotherapy. We developed a safe and clinically translatable irinotecan implant for local delivery to increase its efficacy while minimizing systemic side effects. Irinotecan-loaded implants were manufactured using hot melt extrusion, gamma sterilized at 25 kGy, and characterized for their irinotecan content, release, and drug diffusion. Their therapeutic efficacy was evaluated in a patient-derived xenograft mouse resection model of glioblastoma. Their safety and translatability were evaluated using histological analysis of brain tissue and serum chemistry analysis. Implants containing 30% and 40% w/w irinotecan were manufactured without plasticizer. The 30% and 40% implants showed moderate local toxicity up to 2- and 6-day post-implantation. Histopathology of the implantation site showed signs of necrosis at days 45 and 14 for the 30% and 40% implants. Hematological analysis and clinical chemistry showed no signs of serious systemic toxicity for either implant. The 30% implants had an 80% survival at day 148, with no sign of tumor recurrence. Gamma sterilization and 12-month storage had no impact on the integrity of the 30% implants. This study demonstrates that the 30% implants are a promising novel treatment for glioblastoma that could be quickly translated into the clinic.

Response Surface Methodology for Optimization of Buspirone Hydrochloride-Loaded In Situ Gel for Pediatric Anxiety.

The purpose of the current investigation was to formulate, assess, and optimize oral in situ gels of buspirone hydrochloride (BH) with the specific end goal of expanding the time the medication spends in the stomach, thereby ensuring an extended medication discharge. This would allow the use of a once-a-day dose of liquid BH formulations, which is ideal for the treatment of pediatric anxiety. In situ gels loaded with BH were prepared using various concentrations of sodium alginate (Na alg.), calcium chloride (CaCl2), and hydroxypropyl methylcellulose (HPMC K15M). The in situ gels exhibited the desired consistency, drug distribution, pH, ability to form gel, and prolonged drug release in vitro. The (33) full factorial design was utilized for the revealing of the ideal figures for the selected independent variables, Na alg. (X1), HPMC (X2), and CaCl2 (X3) based on measurements of the viscosity (Y1) and percentage drug release after 6 h (Y2). A pharmacokinetic study of the optimum formulation on rabbits was also performed. The formulation containing 2% of Na alg., 0.9% of HPMC-K15M, and 0.1125% of CaCl2 was selected as the ideal formulation, which gave the theoretical values of 269.2 cP and 44.9% for viscosity and percentage of drug released after 6 h, respectively. The pharmacokinetic study showed that the selected oral Na alg. in situ gel formulation displayed a prolonged release effect compared to BH solution and the marketed tablet (Buspar®), which was confirmed by the low Cmax and high Tmax values. The optimum oral Na alg. in situ gel showed a 1.5-fold increment in bioavailability compared with the drug solution.