Anil B. Jindal

Particle Shape: A New Design Parameter for Passive Targeting In Splenotropic Drug Delivery

The role of particle size and surface modification on biodistribution of nanocarriers is widely reported. We report for the first time the role of nanoparticle shape on biodistribution. Our study demonstrates that irregular shaped polymer lipid nanoparticles (LIPOMER) evade kupffer cells and localize in the spleen. We also demonstrate the macrophage-evading characteristic of the irregular-shaped LIPOMER. Our results suggest particle shape as an important tool for passive targeting of nanocarriers in splenotropic drug delivery.

Microemulsions and Nanoemulsions for Targeted Drug Delivery to the Brain

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.

Synthesis of thiolated alginate and evaluation of mucoadhesiveness, cytotoxicity and release retardant properties

Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate–cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03–324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate–cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate–cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems.

Multi-objective fuzzy mathematical modelling of closed-loop supply chain considering economical and environmental factors

The growing concern for sustainability has forced the researchers and managers to incorporate the environmental and social factors along with the economical factors in the design of supply chains. This paper presents the design and optimization of a multi-objective closed-loop supply chain considering the economical and environmental factors with uncertainty in parameters. The proposed network is modeled as fuzzy multi-objective mixed integer linear programming problem considering multi-customer zones, multi-collection centers, multi-disassembly centers, multi-refurbishing centers, multi-external suppliers, and different product recovery processes; to take care for purchasing cost, transportation cost, processing cost, set-up cost, and capacity constraints simultaneously. The model is solved using an interactive

The effect of particle shape on cellular interaction and drug delivery applications of micro- and nanoparticles

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Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential

ε-constraint method. A case example is solved using LINGO 14.0 to demonstrate the significance and applicability of the developed fuzzy optimization model for closed-loop supply chain.

Nano-natural Products as Anticancer Agents

Asymmetric lipid polymer nanostructures (LIPOMER) comprising glyceryl monostearate (GMS) as lipid and Gantrez AN 119 (Gantrez) as polymer, revealed enhanced splenic accumulation. In the present paper, we attempt to explain the formation of asymmetric GMS LIPOMER using real time imaging. Particles were prepared by precipitation under static conditions using different non-solvent phase compositions. The process was video recorded and the videos converted to time elapsed images using the FFmpeg 0.10.2 software at 25 frames/sec. Non-solvent compositions comprising >30% of IPA/Acetone revealed significant stranding of the solvent phase and slower onset of precipitation(2-6s). At lower concentrations of IPA and acetone, and in non-solvent compositions comprising ethanol/water the stranding phenomenon was not evident. Further, rapid precipitation(<1 s) was evident. Nanoprecipitation based on the Marangoni effect is a result of diffusion stranding, interfacial turbulence, and mass transfer of solvent and non-solvent resulting in solute precipitation. Enhanced diffusion stranding favored by high interaction of GMS and Gantrez(low ΔPol), and the low solubility parameter(Δδtotal) and high mixing enthalpy(ΔHM) of GMS in IPA resulted in droplets with random shapes analogous to an amoeba with pseudopodia, which on precipitation formed asymmetric particles. Asymmetric particles could be readily designed through appropriate selection of solutes and non-solvent phase by modified nanoprecipitation.

Influence of particle shape on plasma protein adsorption and macrophage uptake.

Encapsulation of therapeutic agents in nanoparticles offers several benefits including improved bioavailability, site specific delivery, reduced toxicity and in vivo stability of proteins and nucleotides over conventional delivery options. These benefits are consequence of distinct in vivo pharmacokinetic and biodistribution profile of nanoparticles, which is dictated by the complex interplay of size, surface charge and surface hydrophobicity. Recently, particle shape has been identified as a new physical parameter which has exerted tremendous impact on cellular uptake and biodistribution, thereby in vivo performance of nanoparticles. Improved therapeutic efficacy of anticancer agents using non-spherical particles is the recent development in the field. Additionally, immunological response of nanoparticles was also altered when antigens were loaded in non-spherical nanovehicles. The apparent impact of particle shape inspired the new research in the field of drug delivery. The present review therefore details the research in this field. The review focuses on methods of fabrication of particles of non-spherical geometries and impact of particle shape on cellular uptake, biodistribution, tumor targeting and production of immunological responses.