Showing papers by "Padma V. Devarajan published in 2011"
TL;DR: The reviews discusses the development of ME/NE, design of functional ME/ NE by appropriate selection of primary Me/NE components which could provide improved brain delivery by functioning as stealth agent, absorption enhancer, efflux transporter inhibitor or even facilitate receptor mediated endocytosis.
Abstract: Brain disorders including neurological disorders, inflammatory and infectious conditions of brain, brain cancer and brain stroke pose a significant challenge globally. The blood brain barrier (BBB) an important physiological barrier limits access of drug to the site of action. While passive diffusion and endogenous carrier mediated transport are two important mechanisms for the transport of substances across the BBB into the luminal side, efflux transporters severely limit drug concentration. Drug delivery strategies must address on one hand methods to bypass the BBB and on the other hand methods to overcome efflux transporters. Lipid based nanocarriers, liposomes and solid lipid nanoparticles are widely investigated for brain targeting. Emulsion based lipid nanocarriers like microemulsions (ME) and nanoemulsions (NE) provide an additional advantage of greater bypass of the reticulo-endothelial system with improved brain targeting. More recently the promise of ME and NE for brain delivery has been cited. Oil, surfactants and water are the primary components of ME and NE. ME may additionally comprise cosurfactants. The reviews discusses the development of ME/NE, design of functional ME/NE by appropriate selection of primary ME/NE components which could provide improved brain delivery by functioning as stealth agent, absorption enhancer, efflux transporter inhibitor or even facilitate receptor mediated endocytosis. Engineering functional ME/NE into multifunctional ME/NE as a strategy to further enhance brain targeting is also presented. Functional and multifunctional excipients have been discussed. The possible routes of delivery namely intravenous, oral and intranasal and therapeutic applications of ME/NE designed for brain targeting is also reviewed.
56 citations
TL;DR: The MD simulation method provides a reasonable approximation of drug uptake that will be useful in developing polymer-based drug delivery systems.
Abstract: Drug uptake by polymer was modeled using a molecular dynamics (MD) simulation technique. Three drugs—doxorubicin (water soluble), silymarin (sparingly water soluble) and gliclazide (water insoluble)—and six polymers with varied functional groups—alginic acid, sodium alginate, chitosan, Gantrez AN119 (methyl-vinyl–ether-co-malic acid based), Eudragit L100 and Eudragit RSPO (both acrylic acid based)—were selected for the study. The structures were modeled and minimized using molecular mechanics force field (MM+). MD simulation (Gromacs-forcefield, 300 ps, 300 K) of the drug in the vicinity of the polymer molecule in the presence of water molecules was performed, and the interaction energy (IE) between them was calculated. This energy was evaluated with respect to electric-dipole, van der Waals and hydrogen bond forces. A good linear correlation was observed between IE and our own previous data on drug uptake* [R
2 = 0.65, $$ {\hbox{R}}_{\rm{adj}}^2 = 0.65,{\hbox{R}}_{\rm{pre}}^2 = 0.56, $$
and a F ratio of 30.25, P < 0.001; Devarajan et al. (2005) J Biomed Nanotechnol 1:1–9]. Maximum drug uptake by the polymeric nanoparticles (NP) was achieved in water as the solvent environment. Hydrophilic interaction between NP and water was inversely correlated with drug uptake. The MD simulation method provides a reasonable approximation of drug uptake that will be useful in developing polymer-based drug delivery systems.
48 citations
TL;DR: A series of cinnamide derivatives was designed as potential antimycobacterial agents using molecular hybridization approach and showed good to moderate activity with MIC in the range of 5-150 μM and good safety profile.
42 citations
TL;DR: Evaluation of pullulan-functionalized doxorubicin nanoparticles for asialoglycoprotein receptor-mediated uptake in the Hep G2 cell line suggests extracellular release of DOX as the mechanism of uptake from the nanoparticles.
Abstract: The present study discusses evaluation of pullulan-functionalized doxorubicin nanoparticles for asialoglycoprotein receptor-mediated uptake in the Hep G2 cell line. Doxorubicin hydrochloride (DOX) nanoparticles using polymers of different hydrophobic character, polyethylene sebacate (hydrophobic) and poly (lactic-co-glycolic acid) (intermediate hydrophobicity) with high entrapment efficiency and particle size were prepared by modified nanoprecipitation, using Gantrez AN 119 as complexing agent. Nanoparticles of Gantrez AN 119 were also prepared to represent a hydrophilic polymer. Cell uptake of DOX nanoparticles was found to be comparable to DOX solution irrespective of DOX concentration, nanoparticles size, and pullulan concentration. Furthermore, uptake of nanoparticles functionalized with or without pullulan prepared with polymers of different hydrophobic character revealed comparable uptake. Comparable uptake of DOX solution and DOX nanoparticles functionalized with or without pullulan suggest extracellular release of DOX as the mechanism of uptake from the nanoparticles. In vivo evaluation in hepatic cancer model is therefore essential to confirm the role of pullulan as asialoglycoprotein receptors ligand.
23 citations
Patent•
24 Oct 2011
TL;DR: In this article, the authors proposed a method for the preparation of drug loaded heterogeneous nanosystems resulting from mixing of two monophasic phases, the non-aqueous phase comprising of active agent/s, polymers, lipids, surfactants, solubilizer/s and other excipients and the aqueous phase consisting of buffers, isotonic solutions, sweetners, flavors, etc.
Abstract: The present invention relates to preparation of drug loaded heterogeneous nanosystems resulting from mixing of two monophasic phases, the non-aqueous phase comprising of active agent/s, polymers, lipids, surfactants, solubilizer/s and other excipients and the aqueous phase comprising of buffers, isotonic solutions, sweetners, flavors and other excipients.The novel technique enables formation of stable colloidal particles with high drug loading and predictable size at the time of use. The invention represents a major step in circumventing the technological challenges in the design of colloidal particles which can remain suspended for at least 4h maintaining an effective average particle size of <1μm. The unique delivery system makes part of the active agent/s readily bioavailable and part of the agent is present within the polymeric matrix. The invention is applicable to agent/s that contains electrical group, as the particles are formed due to electrostatic interaction. The novel technique avoids use of organic solvent and can reduce energy requirements compared to the conventional preparation methods. The invention is aimed at the overall improvement of therapeutic efficacy, enhance solubility, enhance oral bioavailability and rapid dissolution for in vivo delivery of the BCS class agent/s. The heterogeneous nanosystems /compositions produced according to the invention can be useful in drug delivery, imaging and diagnosis and can be administered by oral and parenteral route.
3 citations
TL;DR: It was observed that blank lipomer and lipomer DH were safe when administered intravenously at doses 2000mg/kg Bw and 18 mg/kg bw respectively.
Abstract: The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthesized for the treatment of Brucellosis to increase efficacy of the drug. The present study was undertaken to determine the intravenous safety of blank lipomer and Lipomer DH in terms of maximum tolerated dose in rats. It was observed that blank lipomer and lipomer DH were safe when administered intravenously at doses 2000 mg/kg Bw and 18 mg/kg bw respectively.
2 citations