Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers

Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly l-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study

Development of biodegradable polymer based tamoxifen citrate loaded nanoparticles and effect of some manufacturing process parameters on them: a physicochemical and in-vitro evaluation

The aim of the present study was to develop nanoparticles of tamoxifen citrate, a non-steroidal antiestrogenic drug used for the treatment of breast cancer. Biodegradable poly (D, L- lactide-co-glycolide)-85:15 (PLGA) was used to develop nanoparticles of tamoxifen citrate by multiple emulsification (w/o/w) and solvent evaporation technique. Drug-polymer ratio, polyvinyl alcohol concentrations, and homogenizing speeds were varied at different stages of preparation to optimize the desired size and release profile of drug. The characterization of particle morphology and shape was performed by field emission scanning electron microscope (FE-SEM) and particle size distribution patterns were studied by direct light scattering method using zeta sizer. In vitro drug release study showed that release profile of tamoxifen from biodegradable nanoparticles varied due to the change in speed of centrifugation for separation. Drug loading efficiency varied from 18.60% to 71.98%. The FE-SEM study showed that biodegradable nanoparticles were smooth and spherical in shape. The stability studies of tamoxifen citrate in the experimental nanoparticles showed the structural integrity of tamoxifen citrate in PLGA nanoparticles up to 60°C in the tested temperatures. Nanoparticles containing tamoxifen citrate could be useful for the controlled delivery of the drug for a prolonged period

Arsenate and Arsenite Reaction Kinetics with Ferric Hydroxides Using Quantum Chemical Calculations

Received: 01.10.2018. Accepted: 25.10.2018. Published: 31.10.2018.The knowledge of the mechanism involved in the process of adsorption and desorption of arsenate and arsenite with ferric hydroxides is important to address the water toxicity problems and to tackle the adverse effect of these substances in nature. An essential outcome of previous studies on the kinetics of the arsenate adsorption on aluminum and iron oxide was that the adsorption is a two-phase (bi-phase) process. Quantum mechanical calculations using density functional theory were used to determine the thermodynamic variables governing the adsorption process to get an insight into the stability of the complexes formed. The previous investigation showed that the positively charged ferric hydroxide cluster had better stability at neutral pH. The chemisorbed charged monodentate complexes had Gibbs free energy of reaction –55.97 kcal/mol where the bidentate complex formation had Gibbs free energy of reaction –62.55 kcal/mol. The bidentate complex having a negative charge had more Gibbs free energy of reaction compared to uncharged one. The results of the study indicate that Gibbs free energy for the reaction has a significant role in controlling the kinetics of the adsorption and sorption process of arsenate on ferric hydroxide clusters.K. Giri acknowledges financial support from UGC, Govt. of India for Start-up Project Funding. S. Santra and G. V. Zyryanov thank Russian Science Foundation (Ref # 18‑73‑00301) for financial help

Effect of Alkylation on the Kinetic Stability of Arsenodiester and Organoarsenicals against Hydrolysis: A Theoretical Study

Received: 14.06.2018. Accepted: 27.07.2018. Published: 30.07.2018.Arsenic diesters have same structural and chemical properties as Pi (phosphate) diester. Beside this structural similarity, arsenate is not considered by cellular processes to replace phosphate. Quantum calculation reveals that this happens due to very high hydrolysis rate of Asi diester (As–O-bond-based compounds) as compared to Pi, but how organoarsenicals (As–C-bond-based compounds) that are produced by alkylation of Asi survive in highly aqueous tissues of marine organisms? We found that this alkylation results in lower hydrolysis rate of Asi diester. Our work concluded that alkylating effort by our body on Asi is to avoid structural ambiguity with phosphate and excrete out arsenic in the form of organoarsenicals from body

Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation

The current study deals with the development and optimization of ispaghula (Plantago ovata F.) husk mucilage- (IHM-) alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA) to IHM and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), as well as cumulative drug release after 10 hours (R10 h, %), were optimized using 32 factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited 94.43±4.80% w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order) pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration