Potentiation of Brain Bioavailability Using Thermoreversible Cubosomal Formulation.

The aim of the present study was to develop and evaluate intranasal formulations of the thermoreversible fluoxetine cubosomal in situ gel. This gel was intended for permeation and bioavailability enhancement to target the brain effectively by bypassing the blood-brain barrier (BBB). Fluoxetine-loaded cubosomes were prepared by the homogenization method followed by the cold method approach to develop in situ gel. Fluoxetine-loaded cubosomes displayed a higher encapsulation efficiency (82.60 ± 1.25%) than fluoxetine. This might be due to the solubilizing activity of the polymer to cause partitioning of the lipophilic drug into the aqueous phase during the change from the cubic gel phase to cubosomes. In vitro analysis of fluoxetine-loaded cubosomal in situ gel showed a sustained release profile (93.22 ± 2.47%) due to limited diffusion of fluoxetine. The formation of strong affinity bonds of the drug with GMO (drug transporter) decreased the drug release in comparison to that with fluoxetine-loaded cubosomes (90.68 ± 1.74%). The ex vivo drug release profile revealed the drug release of 96.31 ± 2.88% by the end of 24 h. This is attributed to the higher capability of the intranasal cubosomal in situ gel to prolong the retention and enable better permeation through the nasal mucosa. In male Wistar rats, in vivo biodistribution studies for cubosomal in situ gel administered via the intranasal route at a dose of 3.5 mg/kg demonstrated an increase in pharmacokinetic parameters like the AUC (406 ± 75.35 µg/mL), Cmax (368.07 ± 0.23 µg/mL), Tmax (4 h), and t1/2 (14.06 h). The mucoadhesive nature of the in situ gel led to an increase in the residence time of the gel in the nasal mucosa. The biodistribution study of intranasal in situ cubosomal gel improved the bioavailability 2.21-fold in comparison to that with the cubosomal dispersion but 2.83-fold in comparison to that with the drug solution. Therefore, fluoxetine-loaded cubosomal in situ gel proved as a promising carrier for effective transportation of fluoxetine via the intranasal route with significant brain bioavailability.

Success and Complication Rates of Revascularization Procedures for Immature Necrotic Teeth: A Systematic Review.

Frequently, adolescents exhibit instances of immature necrotic teeth, which are identifiable by their slender root walls and unclosed root tips. The lack of a natural narrowing near the root's end creates difficulty when using standard endodontic procedures, making the effective sealing of the immature root canal difficult or impractical. Revascularization therapy surfaces as a prospective strategy for addressing the management of undeveloped, non-vital, immature, necrotic teeth. Notwithstanding this, apexification continues to hold prominence in the preferences of clinicians owing to its perceived predictability in treatment outcomes. A systematic investigation was conducted involving various search engines and databases, covering the period from 2001 to 2023. The main aim of this investigation was to find randomized clinical trials that compared the efficacy of revascularization therapy to apexification for treating immature necrotic teeth. The evaluation included a thorough examination of both clinical and radiographic outcomes assessing the success rates and complications. Out of the 850 identified articles, 15 studies were chosen for comprehensive analysis. Notable dissimilarities were not identified between the revascularization therapy and apexification groups concerning parameters such as rates of periapical healing, overall effectiveness/invalidation, and apical closure. However, concentrating on measurable factors, it became clear that the revascularization treatment group displayed a notable rise in root length compared to the apexification group. Both revascularization endodontic therapy and apexification demonstrated effectiveness in addressing periapical periodontitis healing and open apex closure. Pulp revascularization stood out for its notable efficacy in enhancing root elongation and thickening, all while having a reduced likelihood of treatment being deemed ineffective overall.