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Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER's antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (-32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

Rheumatoid arthritis (RA) is a chronic inflammatory illness affecting the joints. The characteristic of RA is gradual joint deterioration. Current RA treatment alleviates signs such as inflammation and pain and substantially slows the progression of the disease. In this study, we aimed to boost the transdermal delivery of berberine (a natural product) by encapsulating it in chitosan, surface-modified bilosomes nanogel for better management of the inflammation of RA. The chitosan-coated bilosomes loaded with berberine (BER-CTS-BLS) were formulated according to the thin-film hydration approach and optimized for various causal variables, considering the effect of lipid, sodium deoxycholate, and chitosan concentrations on the size of the particles, entrapment, and the surface charge. The optimized BER-CTS-BLS has 202.3 nm mean diameter, 83.8% entrapment, and 30.8 mV surface charge. The optimized BER-CTS-BLS exhibited a delayed-release profile in vitro and increased skin permeability ex vivo. Additionally, histological examination revealed that the formulated BLS had no irritating effects on the skin. Furthermore, the optimized BER-CTS-BLS ability to reduce inflammation was evaluated in rats with carrageenan-induced paw edema. Our results demonstrate that the group treated with topical BER-CTS-BLS gel exhibited a dramatic reduction in rat paw edema swelling percentage to reach 24.4% after 12 h, which was substantially lower than other groups. Collectively, chitosan-coated bilosomes containing berberine have emerged as a promising therapeutic approach to control RA inflammation.

Luteolin is a natural drug used as an antioxidant and anti-inflammatory, but unfortunately, it possesses low water solubility, which hinders its delivery via the skin. The main objective of this study was to prepare a luteolin-loaded nanosuspension by the antisolvent precipitation/sonication technique and study the effects of four stabilizers (two nonionic stabilizers, Pluronic F127 and Tween 80, and two polymeric stabilizers, HPMC and alginate) on the physicochemical properties of the prepared formulations. The selected formulations were incorporated into a gel base to evaluate their skin permeability and anti-inflammatory efficacy. The particle size was in the nanosize range (in the range from 468.1 ± 18.6 nm to 1024.8 ± 15.9 nm), while the zeta potential was negative and in the range from -41.7 ± 6.3 mV to -15.3 ± 1.9 mV. In particular, alginate-stabilized nanosuspensions showed the smallest particle size, the highest zeta potential value, and excellent stability due to the dual stabilizing effects (electrostatic and steric effects). The DSC results revealed a less crystalline structure of luteolin in lyophilized NS2 and NS12. Formulations stabilized by 1% Pluronic (NS2) and 2% alginate (NS12) were incorporated into a carbopol 940 gel base and showed good organoleptic character (homogenous with no evidenced phase separation or grittiness). In vitro dissolution studies showed that NS12 enhanced luteolin release rates, indicating the effect of particle size on the drug release pattern. On the other hand, NS2 showed enhanced skin permeability and anti-inflammatory effect in a carrageenan-induced paw edema model, revealing the surface activity role of the stabilizers. In conclusion, while alginate increased the nanosuspension stability by means of dual stabilizing effects, Pluronic F127 improved the skin delivery and pharmacodynamic efficacy of luteolin.

Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.

Long-acting preparations containing the antipsychotic paliperidone for intramuscular injection has drawn considerable attention to achieve harmless long-term treatment. This study aimed to develop paliperidone loaded polycaprolactone (PCL) nanoparticles and investigate the influence of PCL/drug ratio, stabilizer type, and chitosan coating on physicochemical properties, protein adsorption, and cellular toxicity. Results showed that chitosan coating produced enlarged particle sizes, shifted the surface charges from negative into positive and did not influence encapsulation efficiencies. Chitosan coating relatively sustained the drug release especially in pluronic stabilized formulations. Pluronic F127 based formulations exhibited the least protein adsorption (384.3 μg/mL). Chitosan coating of Tween 80 and polyvinyl alcohol stabilized formulations significantly ( p < 0.05) increased protein adsorption. Cellular viability was concentration-dependent and negatively affected by stabilizers. All formulations did not show cellular death at 1.56 μg/mL. Inflammatory responses and oxidative stress were less affected by Tween 80 compared with other stabilizers. Chitosan minimized all aspects of cellular toxicity. Collectively, stabilizer type and chitosan coating play critical roles in developing safe and effective long-acting PCL nanoparticles intended for parenteral drug delivery. The coated formulations containing Tween 80 and Pluronic F127 as stabilizers are warranted a future in vivo study to delineate its safety and efficacy profiles.