Polymeric drug release control

Kopecek J, Rihova B, Krinick NL. Targetable photoactivatable polymeric drugs. J Control Release 1991 16 137-144. 

M Zandi, A Pourjavadi, S A Hashemi, H Arabi, Preparation of ethyl cellulose microcapsules containing perphenazine and polymeric perphenazine based on acryloyl chloride for physical and chemical studies of drug release control . Polymer Int, 1998 47 413-418... 

H. Maeda, T. Sawa and T. Konno, Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS, /. Control. Release, 74,47-61 (2001). 

H. Maeda, T. Sawa, and T. Konno, Mechanism of tumor-targeted dehvery of macromolec-ular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS, /. Control. Release, 74 (1-3), 47-61,2001 H. Yamamoto, T. Miki, T. Oda, T. Hirano, Y. Sera, M. Akagi, and H. Maeda, Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-maleic acid copolymer, Eur. J. Cancer, 26 (3), 253-260,1990. 

M. Nakayama, T. Okano, T. Miyazaki, F. Kohori, K. Sakai, and M. Yokoyama, Molecular design of biodegradable polymeric micelles for temperature-responsive drug release, / Control Release, 115 (1), 46-56, 2006. 

Rate of hydration of the polymeric materials has been shown to be an important consideration in regard to drug release. Gilding and Reed (24) demonstrated that water uptake increases as the glycolide ratio in the copolymer increases. The extent of block or random structure in the copolymer can also affect the rate of hydration and the rate of degradation (25). Careful control of the polymerization conditions is required in order to afford reproducible drug release behavior in a finished product. Kissel (26) showed drastic differences in water uptake between various homopolymers and copolymers of caprolactone, lactide, and glycolide. 

H. Goodman and G. Banker. Molecular-scale drug entrapment as a precise method of controlled drug release I Entrapment of cationic drugs by Polymeric flocculation, J. Pharm. Sci. 59 1131-1137, 1970. 

Bulmus V, Woodward M, Lin L, Murthy N, Stayton P, Hoffman A (2003) A new pH-responsive and glutathione-reactive, endosomal membrane-disruptive polymeric carrier for intracellular delivery of biomolecular drugs. J Control Release 93 105-120... 

With continuous development of systems for controlled drug release, new materials are being used whose influence on peptide stability must be carefully examined. Thus, the model hexapeptide Val-Tyr-Pro-Asn-Gly-Ala (Fig. 6.30) embedded in poly (vinyl alcohol) and poly(vinyl pyrrolidone) matrices had rates of deamidation that increased with increasing water content or water activity, and, hence, with decreasing glass transition temperature (Tg). However, the degradation behavior in the two polymers differed so that chemical reactivity could not be predicted from water content, water activity, or T% alone. Furthermore, the hexapeptide was less stable in such hydrated polymeric matrices than in aqueous buffer or lyophilized polymer-free powders [132],... 

Buccal dosage forms can be of the reservoir or the matrix type. Formulations of the reservoir type are surrounded by a polymeric membrane, which controls the release rate. Reservoir systems present a constant release profile provided (1) that the polymeric membrane is rate limiting, and (2) that an excess amoimt of drug is present in the reservoir. Condition (1) may be achieved with a thicker membrane (i.e., rate controlling) and lower diffusivity in which case the rate of drug release is directly proportional to the polymer solubility and membrane diffusivity, and inversely proportional to membrane thickness. Condition (2) may be achieved, if the intrinsic thermodynamic activity of the drug is very low and the device has a thick hydrodynamic diffusion layer. In this case the release rate of the drug is directly proportional to solution solubility and solution diffusivity, and inversely proportional to the thickness of the hydrodynamic diffusion layer. 

For an erosion-induced drug delivery system compactable cellulose ethers are suitable polymers [103]. Drug release, which is controlled by the erosion/dissolution of these polymeric layers, may be pH-dependent if an acid or basic polymer is used. 

Muscles contract and expand in response to electrical, thermal, and chemical stimuli. Certain polymers, such as synthetic polypeptides, are known to change shape on application of electric current, temperature, and chemical environment. For instance, selected bioelastic smart materials expand in salt solutions and may be used in desalination efforts and as salt concentration sensors. Polypeptides and other polymeric materials are being studied in tissue reconstruction, as adhesive barriers to prevent adhesion growth between surgically operated tissues, and in controlled drug release, where the material is designed to behave in a predetermined matter according to a specific chemical environment. 

Chung JE, Yokoyama M, Okano T. Inner core segment design for drug delivery control of thermo-responsive polymeric micelles. J Controlled Release 2000 65 93-103. 

Polymeric oxazolines have also been used as vehicles for controlled drug release ° ° and DNA transfection, as polymeric micelles, which serve as carriers for drug transport (e.g., paclitaxel), and as formulation additives for controlled-release of insecticides. ... 

This contribution will provide a review of polylectrolytes as biomaterials, with emphasis on recent developments. The first section will provide an overview of methods of synthesizing polyelectrolytes in the structures that are most commonly employed for biomedical applications linear polymers, crosslinked networks, and polymer grafts. In the remaining sections, the salient features of polyelectrolyte thermodynamics and the applications of polyelectrolytes for dental adhesives and restoratives, controlled release devices, polymeric drugs, prodrugs, or adjuvants, and biocompatibilizers will be discussed. These topics have been reviewed in the past, therefore previous reviews are cited and only the recent developments are considered here. 

This book is a companion volume to Pharmaceutical Technology Controlled Drug Release, Volume 1, edited by M.H.Rubinstein and published in 1987. It focused on the different types of polymeric materials used in controlled release. This book extends these concepts to include drug properties, design and optimization, coating, the effect of food and pharmacokinetics. It also reflects the growing interest in biodegradable polymers in oral and topical formulations and the use of sterile implants. 

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