LORNOXICAM-LOADED NANOSPONGES FOR CONTROLLED ANTI-INFLAMMATORY EFFECT: IN VITRO/IN VIVO ASSESSMENT

Objective: To design a controlled topical delivery system of lornoxicam (LX) in order to enhance skin permeation and treatment efficacy. Nanosponges were selected as a novel carrier for this purpose. Methods: Nanosponges were formulated via the emulsion solvent evaporation method using ethyl cellulose (polymer) and polyvinyl alcohol (surfactant). Nanosponge dispersions were characterized for colloidal properties, entrapment efficiency and in vitro release study. The nanosponge formulation (LS1) was then incorporated into carboxymethyl cellulose sodium hydrogels and evaluated for pH, viscosity and in vitro drug release. Skin irritation was evaluated, and anti-inflammatory activity was assessed via rat hind paw edema method. Results: Nanosponges were in the nano-sized range and attained a uniform round shape with a spongy structure. LS1exhibited the highest LX release after 6 h, so it was incorporated as hydrogel. Formulated hydrogels showed acceptable physicochemical parameters (pH, drug content and rheological properties). Skin irritation testing proved LX-loaded nanosponge hydrogel formulation (G1) to be non-irritant. In vivo study revealed an enhanced anti-inflammatory activity of G1 for 6 h (p<0.001). Conclusion: The developed nanosponge hydrogel is an efficient nanocarrier for improved and controlled topical delivery of LX

Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics