Padma V. Devarajan

HIV/AIDS is an intracellular infection of the macrophages and play an important role in dissemination of the infection across the body. Nevirapine although remains a drug of choice for the treatment; the life threatening hepatotoxicity limits its clinical application. Present study reports preparation, characterization and surface modification of nevirapine nanoparticles. The anti-HIV potential of gold nanoparticles prompted us to prepare nevirapine loaded gold nanoparticles using a biodegradable in house polymer polyethylene sebacate. Core shell nevirapine nanoparticles comprising gold in the core and nevirapine loaded polyethylene sebacate as shell (average particle size ~ 250nm) were successfully prepared using double emulsion solvent evaporation method followed by surface modification with macrophage mannose receptor targeting ligand Concanavalin A by simple incubation. Concanavalin A was selected as a targeting ligand as the molecular docking studies of Concanavalin A with excipients suggested possible interactions. Concanavalin A anchoring was confirmed by spectrofluoremetrically, FTIR and zeta potential analysis. UV analysis of nevirapine nanoparticles revealed shell formation and NVP loading. SEM-EDAX analysis indicated presence of Au in the spherical nanoparticles while TEM confirmed formation of core shell nanoparticles with smooth surface. DSC and XRD analysis demonstrated amorphization of NVP in nanoparticles. Residual solvent analysis complied ICH standards. Nanoparticles with and without CON exhibited sustained release till 24 h in phosphate buffer pH 7.4 and good stability for 1 year as per ICH guidelines.

The present study discusses scale up of asymmetric doxycycline hydrochloride (DH) LIPOMER (lipid polymer nanostructures) by nanoprecipitation. A solution of Doxycycline hydrochloride , Glyceryl monostearate and Gantrez AN119 in tetrahydrofuran was added to a non solvent phase comprising Isopropyl alcohol and water, under stirring to obtain doxycycline hydrochloride LIPOMER. At the 1X (400mg solids) scale the process was optimized to increase solute concentration and solvent to non solvent ratio while decreasing total solvent volume. At 10X scale varying the agitator speed, agitator type and number of baffles, at a maximum addition rate of 4mL/min, particles with an average size of ~455 nm were obtained with a 45° pitched six blade turbine agitator and baffles. Using the principle of geometric similarity the 10X batch, gradually scaled up to 240X (96 gm solids), revealed average particle size in the range 454 to 510 nm with >80% entrapment efficiency (EE).Using air atomization introducing small globules of the solvent phase (100 mL/min), in to the non solvent phase enabled  a size of ~340 nm with 84%  EE at  120X and 240X. DH LIPOMER exhibited good stability and asymmetric shape. More importantly LIPOMER in the desired size range (~300-600nm) for RES uptake was optimized.  Air atomization presents a simple and practical approach for scaleup of nanoparticles by nanoprecipitation.

The present study reports the role of the nanoparticulate drug delivery systems of rifampicin-lopinavir combinations on enhanced bioavailability of the drugs following oral administration. Entrapping both drugs in the ratio 1:1 is an additional objective. Poly (ethylene sebacate), a novel hydrolytically stable, nonionic, biocompatible and biodegradable, non-mutagenic and non-genotoxic polymer was selected for the study. PLGA and PLA were selected for comparative evaluation. Nanoparticles with adequate drug loading and particle size 350-450nm were developed and freeze dried using a combination of trehalose and lutrol-f-68 as cryoprotectant and characterized for zeta potential, hydrophobicity, SEM, DSC, pXRD etc. Nanoparticles found to be stable as per ICH guidelines. Pharmacokinetic evaluation of RIF-LOPI PES and PLGA nanoparticles revealed comparable plasma drug concentration, delayed Tmax and enhanced oral bioavailability, PLA nanoparticle revealed significantly higher bioavailability. T1/2 values were significantly higher with the nanoparticles for both RIF and LOPI. Following oral administration revealed high concentration of drugs in the RES organs lungs, liver and spleen compared to plain drugs was observed. The high bioavailability of both RIF and LOPI confirms the ability of nanoparticles both to enhance drug absorption and also provide protection in vivo. This protective effect of the nanoparticles enabled high bioavailability of LOPI despite being in combination with RIF an inducer of cytochrome P450.