Solid lipid nanoparticles (SLNs) are promising drug delivery vehicles for the delivery of various drugs, especially poorly water-soluble drugs. However, the aqueous stability, drug release, and biocompatibility of SLNs are some of the issues that need attention. In this work, curcumin-loaded SLNs were prepared, and morphology, particle size, and entrapment efficiency were studied. For this, two amino acid-derived lipids were developed. The effect of the polarity of the lipid head on the aqueous stability of the SLN dispersion was investigated. Based on the stability, particle size, and polydispersity, an optimum formulation was obtained. The curcumin entrapment efficiency of the SLNs was found to be greater than those reported in the literature. The entrapped curcumin, as well as curcumin-loaded SLN suspensions, exhibited improved storage stability. The in vitro release kinetics indicated an enhanced rate of drug release in the case of curcumin-loaded SLNs consisting of the lipid containing −OH groups at the lipid head. The pure lipid and the blank SLN were found to have no significant cytotoxicity, but curcumin and curcumin-loaded SLNs induced cell death in a concentration-dependent manner in both human prostatic adenocarcinoma PC3 cell line and human breast carcinoma MCF7 cell line. This study has proposed a potential semisynthetic lipid for the stable SLN suspension for the delivery of curcumin.

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The entire study validates ZINC62579975 as a potent candidate molecule for PDE9A inhibition. The present study provides a roadmap for future drug designing of more potent xanthine derivatives. This study also explores the potential of xanthine scaffold in future drug development process.

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Background: Matrix metalloproteinase 1 is zinc dependent endopeptidase playing important role in the controlled breakdown of extracellular matrix in normal physiological condition resulting in maintenance of homeostasis. Dysregulation of MMP1 leads to progression of various pathological conditions as cancer, rheumatoid arthritis, cardiovascular disease, skin damage and fibrotic disorder. Thus, MMP1 inhibition may prove to be potential drug target. Many synthetic MMP1 inhibitors are available, but its clinical applicability is hindered by lack of substrate specificity. Hence, inhibitors from natural products have gained widespread attention. Objective: The present study attempts screening of novel MMP1 inhibitors from ZINC database based on experimentally reported natural inhibitors of MMP1 as scaffold. Method: Molecular docking study was performed with 19 experimentally reported natural inhibitors spanning across nine different classes followed by virtual screening using the selected compounds. The selected compounds were subjected to molecular dynamics simulation. Results: Twenty compounds were screened with a cut-off of -9.0 kcal/mol of predicted free energy of binding, which further converged to 6 hits after docking studies. After comparing the docking result of 6 screened hits, two best compounds were selected. ZINC02436922 had the best interaction with six hydrogen bond formation to a relatively confined region in the S1’site of MMP1 and -10.01 kcal/mol of predicted free energy of binding. ZINC03075557 was the second-best compound with -9.57 kcal/mol predicted binding free energy. Molecular dynamics simulation of ZINC02436922 and ZINC03075557 corroborates docking study. Conclusion: This study brings out phenolic compounds ZINC02436922 and ZINC03075557 as potential MMP1 inhibitors.