Fabrication of dual drug loaded bilayered chitosan based composite scaffolds as osteochondral substitutes and evaluation of in vitro cell response using the MC3T3 pre-osteoblast cell line

Osteochondral defects are relatively common in weight-bearing joints of the lower extremities and require multiple approaches of treatment. This work is focused on designing three-dimensional (3D) bilayered scaffolds fully integrating a top chitosan/hydroxypropylmethyl cellulose layer (CS/HPMC) mimicking cartilage and a bottom chitosan/hydroxypropylmethyl cellulose/nano-hydroxyapatite layer (CS/HPMC/nHAp) imitating bone for the treatment of osteochondral defects prepared by freeze drying. Additionally, an anti-inflammatory drug (in the bottom layer) and an antibiotic drug (in the top layer) are incorporated in the form of microspheres and nanofibers, respectively, into these scaffolds to diminish/prevent post-surgical inflammation/infection through sustained release of the drugs. The scaffolds were characterized by a variety of techniques. FT-IR analysis confirmed that there is no/weak interactions between the components, SEM images showed that both layers of the scaffolds have homogenous pore distribution, and scaffolds exhibited reproducible swelling and degradation behavior. Drug release was shown to take place over a period of 14 days in PBS. The scaffolds supported the growth and proliferation of MC3T3 pre-osteoblast cells in vitro and have potential for use in vivo application in the future

Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers

© 2020 Pakistan Journal of Pharmaceutical Sciences. All rights reserved. The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ

Synthesis, characterization and docking studies of amide ligands as anti-leishmanial agents

Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protease enzyme and to evaluate their intended biological activity. A3D model of an enzyme was generated via homology modeling and series of novel amide ligands were synthesized by using a short high yield process, subsequently, analyzed in-silico and in-vitro anti-leishmanial activities. Characterization and identification was accomplished via NMR (H1& C13), infrared and mass spectroscopic techniques. Among all compound (4) was found to show significant activity (IC50 58±0.01) against Leishmania major (L. major) species. Furthermore, docking studies confirmed the inhibition of a targeted enzyme that supported the interaction of potent compound (4) with key residues (aspartic protease) via hydrogen bonds. Present study conferred about novel compound (4) as a promising compound to antagonize L. major activities in future