Quality by design for sumatriptan loaded nano-ethosomal mucoadhesive gel for the therapeutic management of nitroglycerin induced migraine.

Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1ß and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain.

Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation.

OBJECTIVES: Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated. RESULTS: RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs. CONCLUSIONS: All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.