Yashwant Pathak

Study of Rosin and Rosin esters as coating materials

Rosin esters were prepared by heating glycerol, sorbitol and mannitol. Aspirin granules were coated with solution of Rosin and Rosin esters in acetone. The coated granules were studied for moisture absorption, dissolution studies, and ageing studies. The results showed that rosin-coated granules release less than 10% drug in gastric media in 3 h and more than 75% drug in 15 min in intestinal media. Rosin can be used as enteric coating material. Rosin esters give quick release in gastric media and delayed release in intestinal media. Ageing does not have a significant effect in release characteristics. Rosin and Rosin esters are widely used as film-forming plasticizers for moisture protection and find use in chlorinated rubber, vinyl resins, paints and varnishes. Glycerol ester of Rosin has been used as an anhydrous binding agent in tablet formulation (Surowiecki et al., 1971). A formula is patented for repeat action beadlets using abietic acid-type Rosin and Zein (Butler and Vance, 1968). This communication explains the application of Rosin and Rosin esters as coating materials. It was found that Rosin can be used for moisture protection and enteric coating purpose while Rosin esters can be used for controlled release. Rosin esters of glycerol (Kogan, 1932) mannitol and sorbitol (Brown and Geopp, 1938) were prepared by heating Rosin (4 parts) and glycerol (1 part) at 210-220°C. Heating was continued until there was no further drop in acid value of the sample withdrawn from the reaction. The whole mass was poured in water, to remove excess of alcoholic compound, with constant stirring, filtered and dried at 50°C in the oven overnight.

Degradation of Materials in the Biological Environment

Publisher Summary This chapter introduces biodegradation issues for a number of classes of materials. Biodegradation is the chemical breakdown of materials by the action of living organisms that leads to changes in physical properties. It is a concept of vast scope, ranging from the decomposition of environmental waste involving microorganisms to the host-induced deterioration of biomaterials in implanted medical devices. The calcification of biomaterial implants is an important pathologic process affecting a variety of tissue-derived biomaterials as well as synthetic polymers in various functional configurations. The pathophysiology has been partially characterized with a number of useful animal models; a key common feature is the involvement of devitalized cells and cellular debris. To understand the biological degradation of implant materials, synergistic pathways should be considered. Degradation products can alter the local pH, stimulating further reaction. The hydrolysis of polymers can generate more hydrophilic species leading to polymer swelling and entry of degrading species into the bulk of the polymer.

Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228-270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery.

Study of rosin glycerol esters as microencapsulating materials

Rosin esters were prepared by heating rosin with glycerol and intermediate reaction products with different acid values were withdrawn. Salicylic acid granules were encapsulated using a 10 per cent solution of rosin esters in acetone. The coated microcapsules were evaluated for moisture absorption, flow properties and dissolution studies. The results showed that rosin and rosin-glycerol intermediates with acid values of 122, 105 and 55 had excellent moisture protection properties. Dissolution studies showed that these could be used for delayed release of drug.

Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for brain cancer.

Gliomas are some of the most aggressive types of cancers but the blood–brain barrier acts as an obstacle to therapeutic intervention in brain-related diseases. The blood–brain barrier blocks the permeation of potentially toxic compounds into neural tissue through the interactions of brain endothelial cells with glial cells (astrocytes and pericytes) which induce the formation of tight junctions in endothelial cells lining the blood capillaries. In the present study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA nanoparticle, show its in vitro drug release data along with cytotoxicity data in C6 and RG2 cells, and investigate its trans-blood–brain barrier permeation through the establishment of a Transwell cellular co-culture. We show that the docetaxel-loaded nanoparticle’s size enables its trans-blood–brain barrier permeation; the nanoparticle exhibits a steady, sustained release of docetaxel; the drug is able to induce cell death in glioma models; and the glutathione-coated nanoparticle is able to permeate through the Transwell in vitro blood–brain barrier model.

Artificial Neural Network in Drug Delivery and Pharmaceutical Research

Artificial neural networks (ANNs) technology models the pattern recognition capabilities of the neural networks of the brain. Similarly to a single neuron in the brain, artificial neuron unit receives inputs from many external sources, processes them, and makes decisions. Interestingly, ANN simulates the biological nervous system and draws on analogues of adaptive biological neurons. ANNs do not require rigidly structured experimental designs and can map functions using historical or incomplete data, which makes them a powerful tool for simulation of various non-linear systems.ANNs have many applications in various fields, including engineering, psychology, medicinal chemistry and pharmaceutical research. Because of their capacity for making predictions, pattern recognition, and modeling, ANNs have been very useful in many aspects of pharmaceutical research including modeling of the brain neural network, analytical data analysis, drug modeling, protein structure and function, dosage optimization and manufacturing, pharmacokinetics and pharmacodynamics modeling, and in vitro in vivo correlations. This review discusses the applications of ANNs in drug delivery and pharmacological research.

Triamcinolone acetonide nanoparticles incorporated in thermoreversible gels for age-related macular degeneration

Abstract Age-related macular degeneration (AMD) is one of the leading causes of blindness in the US affecting millions yearly. It is characterized by intraocular neovascularization, inflammation and retinal damage which can be ameliorated through intraocular injections of glucocorticoids. However, the complications that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this interesting territory for the development of novel drug delivery systems (DDS). In the present study, we described the development of a DDS composed of triamcinolone acetonide-encapsulated PEGylated PLGA nanoparticles (NP) incorporated into PLGA–PEG–PLGA thermoreversible gel and its use against VEGF expression characteristic of AMD. We found that the NP with mean size of 208 ± 1.0 nm showed uniform size distribution and exhibited sustained release of the drug. We also demonstrated that the polymer can be injected as a solution and transition to a gel phase based on the biological temperature of the eye. Additionally, the proposed DDS was non-cytotoxic to ARPE-19 cells and significantly reduced VEGF expression by 43.5 ± 3.9% as compared to a 1.53 ± 11.1% reduction with triamcinolone. These results suggest the proposed DDS will contribute to the development of novel therapeutic strategies for AMD.

Resveratrol and Omega-3 Fatty Acid: Its Implications in Cardiovascular Diseases

The present review aims at summarizing the major therapeutic roles of resveratrol and omega-3 fatty acids (O3FAs) along with their related pathways. This article reviews some of the key studies involving the health benefits of resveratrol and O3FAs. Oxidative stress has been considered as one of the most important pathophysiological factors associated with various cardiovascular disease conditions. Resveratrol, with the potent antioxidant and free radical scavenging properties, has been proven to be a significantly protective compound in restoring the normal cardiac health. A plethora of research also demonstrated the reduction of the risk of coronary heart disease, hypertension, and stroke, and their complications by O3FAs derived from fish and fish oils. This review describes the potential cardioprotective role of resveratrol and O3FAs in ameliorating the endoplasmic reticulum stress.

Polymeric Controlled Release of Cardiovascular Drugs

Controlled release drug-polymer implants have been useful for a variety of cardiovascular disease processes. Implanting a controlled release system at the site of a pathologic focus results in regional drug administration being optimized and the chance for systemic side effects greatly reduced. The general formulations, which have been useful, include nondegradable polymers such as silicone rubbers, polyurethanes, and ethylene:(vinyl acetate). In addition, biodegradable matrices composed of compounds such as high molecular weight polyanhydrides have also been valuable. These polymers may be combined with dispersed or dissolved drugs to form matrix systems, which release contained agents based on either diffusion or biodegradation or both. Furthermore, reservoir configured controlled release systems, with rate limiting membranes and refilling capability, also represent an important therapeutic advantage. Controlled release systems have been demonstrated by our group to be advantageous for the therapy of ventricular arrhythmias, cardiovascular calcification, and prevention of cardiac transplantation rejection. In addition, the work of others has demonstrated controlled release implants to be valuable for preventing prosthetic valve endocarditis and for preserving pacemaker lead electrical function. Future controlled release systems will be based on unique agents, advanced reservoir systems, and feedback-modulation capabilities.

Effect of pH on the release characteristics of pentaestergum microcapsules and a study of dissolution kinetics

Rosin and rosin esters have excellent film-forming properties. Pentaerythritol-rosin ester (penta-ester gum) is found to be useful as moisture-protecting material with delayed release of drug. This communication relates the effect of pH on the release characteristics of a drug from penta-ester gum coated microcapsules. Salicylic acid granules were encapsulated using a 10 per cent solution of penta-ester gum in acetone. The microcapsules were evaluated for their drug release characteristics. Various pH media (pH 1.2, 3.0, 5.0, 7.2 and 8.0) were used. The results showed that penta-ester gum exhibits excellent resistance to higher pH levels and can be used for the sustained release of the drug. Dissolution rate constants were calculated and they agree with the assumption of Hixson and Crowells cube-root equation.