Avi Domb

Biodegradable block copolymers

Recently, block copolymers have got tremendous impetus on the ongoing research in the area of drug delivery technology, due to their capability to provide a biomaterial having a broad range of amphiphilic characteristics, as well as targeting the drugs to specific site. This article is an attempt to review applications of block copolymers in surface modification, drug targeting, nano and microparticles, hydrogels, micelles etc. The physicochemical properties of block copolymers and various synthetic routes for block copolymers are also discussed.

Pharmaceutical Polymeric Controlled Drug Delivery Systems

Drug delivery systems have taken a great impetus to deliver a drug to the diseased lesions. Although this concept is not new great progress has recently been made in the treatment of a variety of diseases. A suitable carrier is needed to deliver a suitable and sufficient amount of the drug to a targeted point, hence, various kinds of formulations are being constantly developed. This paper reviews the present state of art regarding the synthetic methods and characterization of nanoparticles, the suitability of polymeric systems for various drugs, drug loading and drug release properties of various systems such as nanoparticles, hydrogels, microspheres, film and membranes, tablets, etc. The purpose of this review is to summarize the available information so that it will be helpful to beginners and serve as a useful tool for active researchers involved in this area.

Exploiting EPR in Polymer Drug Conjugate Delivery for Tumor Targeting

Treatment of tumor tissue without affecting normal cells has always been formidable task for drug delivery scientists and this task is effectively executed by polymer drug conjugate (PDC) delivery. The novelty of this concept lies in the utilization of a physical mechanism called enhanced permeability and retention (EPR) for targeting tumors. EPR is a physiological phenomenon that is customary for fast growing tumor and solves the problem of targeting the miscreant tissue. PDCs offer added advantages of reduced deleterious effects of anticancer drugs and augmentation of its formulation capability (e.g. Solubility). There are now at least eleven PDCs that have entered phase I/II/III clinical trial as anticancer drugs. PDCs once entered into the tumor tissue, taking advantage of EPR, are endocytosed into the cell either by simple or receptor mediated endocytosis. Various polymeric carriers have been used with hydrolyzable linker arm for conjugation with bioactive moiety. The hydrolyzable linkages of PDC are broken down by acid hydrolyses of lysosomes and releases the drug. High concentrations of the chemotherapeutic agent are maintained near the nucleus, the target site. Passive targeting by PDCs is due to the physiological event of EPR, which is becoming one of the major thrust areas for targeting solid tumors.

Perivascular delivery of heparin for the reduction of smooth muscle cell proliferation after endothelial injury.

Thin flexible sheets composed of poly(lactic acid) (PLA) laminated polyanhydride, poly(erucic acid dimer-sebacic anhydride) (P(EAD-SA)), loaded with heparin were evaluated in vitro and in vivo. PLA was used for coating the polyanhydride to improve the release profile and improve the strength of the films. Heparin was released constantly for 20 days from PLA-coated 2% loaded P(EAD-SA). The uncoated film of P(EAD-SA) released heparin for only 4 days. The localized delivery of heparin around the carotid artery was investigated by implanting polymer loaded with [3H]heparin around the carotid artery of rats and the heparin release and tissue distribution was monitored. The maximum heparin concentration in the artery exposed to the drug was on day 4 for the P(EAD-SA) uncoated device (fast releasing system) and day 11 for the coated devices. The control artery, the uncovered segments of the artery, and the surrounding tissue contained negligible amounts of radioactivity. These data confirm that heparin was delivered locally without systemic exposure. Two independent animal studies were conducted to evaluate the effectiveness of these heparin-releasing devices. In both studies the balloon catheter injury in a rat model was used. After inflicting an injury to the common carotid, a matrix oriented with its long axis along the artery was placed under the injured portion of the vessel. In both studies the treated rats showed a very thin layer of neointima where the control group showed a significant reduction of the artery internal diameter with SMC neointima ratio greater than 1.

Fatty acid based biodegradable polymer

Synthetic polymers have become an indispensable part of the daily‐life of human beings and the biodegradable class of polymers hold immense value in therapeutics. Fatty acid incorporation in biodegradable polymers renders flexibility, low melting point, hydrophobicity, and pliability properties. At the same time, degradation into naturally occurring compounds makes them environmentally friendly besides their utility in various applications like drug delivery and as implantable devices. Fatty acid monomers are integrated in the polymeric chain using carboxylic acid functional groups. Most fatty acids are monofunctional in nature and act only as chain terminator during polymerization. This limitation has been overcome by the dimerization of unsaturated fatty acids or by creating a functional group on the monomers. The most recent addition to this series is ricinoleic acid based polyanhydrides and copolyesters. In this article, the synthesis methods, the physical properties, the degradation, the stability, and the toxicological aspect and applications of each class of fatty acid based polymers are discussed.

Drug release from a new family of biodegradable polyanhydrides

Abstract Studies investigating the mechanism of drug release from poly (fatty acid dimer:sebacic acid) {p (FAD : SA)} polyanhydride are described. Acid orange (A.O.), a hydrophilic dye and Rhodamine B Base, a hydrophobic dye, were used as models. Light microscopy indicates there is a drug depleted zone which grows wider with time. The effect of drug incorporation method on release was also investigated. An emulsion method greatly reduced A.O.s ‘burst effect’. The effect of copolymer properties (e.g., hydrophobicity, crystallinity), drug properties (e.g., solubility) and drug loading on release was also investigated. A.O. release was affected by copolymer composition, and exhibited faster release than the more hydrophobic dye, Rhodamine B Base. Correlations between drug release and underlying polymer erosion are also described.

A Novel Device for Protecting Rectum During Prostate Cancer Irradiation: In Vivo Data on a Large Mammal Model

PURPOSE Hypofractionation schemes and associated higher rectal doses have evoked the need for improved protection of the rectum during prostate cancer irradiation. MATERIALS AND METHODS An implantable, biodegradable, inflatable, preshaped triangular balloon of commercially used poly(L-lactide-co-epsilon-caprolactone) co-polymer material was developed to provide separation between prostate and rectum. Biocompatibility and degradability of the balloon implanted subcutaneously or perineally, and in the context of transperineal implantation and local irradiation were evaluated in several in vivo studies. RESULTS The device was found to be biocompatible in subcutaneously implanted rabbits up to 42 days, in a transperineally implanted dog up to 12 months and in 8 transperineally implanted pigs up to 6 months. Upon inflation in situ the balloon separated the tissues, remained inflated for several months and subsequently biodegraded. No systemic or local toxicity was noted, as shown by histopathology. Device insertion into the perineal area using a dedicated introductory kit was convenient and feasible. Three-month followup in irradiated pigs that received 15 Gy in 3 fractions 1 week apart showed a stable balloon position with no local or systemic side effects. CONCLUSIONS This novel device was safe and effective for its intended use of separating tissues for a desired duration. A clinical study will commence to evaluate the safety and efficacy of this device during irradiation in patients with prostate cancer.

Structure and Biological Activity of Heparinoid

Heparin is a biogenic anionic charged sulfated polysaccharide that has a range of desired activities including inhibition of tumor metastasis and inhibition of restenosis. However, its clinical use is limited to treating blood-clotting disorders. Anionic macromolecules called heparinoids have been investigated with the objective of developing heparin-like molecules with reduced anti-coagulant activity and selective anti-metastasis and anti-restenosis activity. This mini-review summarizes the synthesis and biological activity of the main synthetic heparinoids reported in the past three decades.