Sanders / Hendren Protein Delivery

Physical Systems
1. Auflage 2005
ISBN: 978-0-306-46803-2
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 10, 447 Seiten, eBook

Reihe: Pharmaceutical Biotechnology

Thirteen chapters by industrial and academic authorities in this rapidly evolving field present detailed case histories and reviews of current sophisticated protein-drug delivery technologies. Highlights include a comprehensive overview of insulin delivery and a discussion of the use of biodegradable microspheres.

Zielgruppe

Research

Autoren/Hrsg.

Sanders, Lynda M.

Hendren, R. Wayne

Inhaltsverzeichnis

Protein Delivery from Biodegradable Microspheres.- Degradable Controlled Release Systems Useful for Protein Delivery.- Delivery of Proteins from a Controlled Release Injectable Implant.- Protein Delivery from Nondegradable Polymer Matrices.- Diffusion-Controlled Delivery of Proteins from Hydrogels and Other Hydrophilic Systems.- Poly(ethyleneglycol)-Coated Nanospheres: Potential Carriers for Intravenous Drug Administration.- Multiple Emulsions for the Delivery of Proteins.- Transdermal Peptide Delivery Using Electroporation.- Protein Delivery with Infusion Pumps.- Oral Delivery of Microencapsulated Proteins.- Controlled Delivery of Somatotropins.- Insulin Iontophoresis.- Insulin Formulation and Delivery.

Leseproben

Chapter 3
Delivery of Proteins from a Controlled Release Injectable Implant (p. 93-94)

GeraldL. Yewey, Ellen G. Duysen,
S. Mark Cox, and Richard L. Dunn

1. THE ATRIGEL™ DRUG DELIVERY SYSTEM

Development of controlled release systems for the delivery of recombinant proteins remains a critical research challenge for the biotechnology industry. Current therapies with these biopharmaceutical agents require frequent injections or infusion owing to the short half-lives of the proteins (Bodmer et al., 1992). Biodegradable implants and microspheres for parenteral administration could extend the half-life of serum-labile proteins and provide an effective mechanism for localized as well as systemic delivery. Although such sustained release therapies may result in higher formulation costs, they have the potential to reduce overall medical costs by decreasing the frequency of administration. They are also more convenient for the patient to use, with a resulting improvement in compliance. Biodegradable systems that allow repetitive courses of therapy to be administered without the need for a subsequent medical procedure to remove the device contribute even more to lower costs.

Recently, a liquid polymer system (ATRIGEL™) has been developed which has both the simplicity and control of solid biodegradable implants and the injectability of microspheres for delivering drugs (Dunn et al., 1992). This drug delivery system combines a biodegradable polymer with a biocompatible solvent, resulting in a solution that can be injected using standard syringes and needles. When the system contacts physiologic fluid, the polymer precipitates as the solvent diffuses into the surrounding tissues. As a result, a biodegradable polymeric implant is formed. For controlled release applications, a drug can be incorporated into the delivery system. The incorporated drug is physically entrapped within the precipitated polymer matrix and is then slowly released. The polymer type, concentration, and molecular weight as well as the carrier solvent, drug load and formulation additives each influence the release kinetics. Manipulation of these formulation variables provides diverse drug delivery profiles as well as polymer biodegradation rates for specific applications.

Candidate biodegradable polymers for use in the drug delivery system include homopolymers of poly( DL -lactide) (PLA) and copolymers of poly(DL -lactide-co-glycolide) (PLG) and poly(DL-lactide-co-caprolactone) (PLC). These polymers are similar in chemical composition to biodegradable sutures and have been well characterized in the literature (Kulkarni et al., 1971, Cutright et al., 1971, Gourlay et al., 1978, Rice et al., 1978, Nakamura et al., 1989). They are well tolerated in the body and generally accepted as safe by the medical/pharmaceutical community. Biodegradation of the polymers is effected by their hydrolysis to lactic, glycolic, and hydroxycaproic acids, respectively. These are either metabolized by the Krebs (or tricarboxylic acid) cycle to CO2 and H2O (Brady et al., 1973, Gilding, 1981, Woodward et al., 1985, Hollinger and Battistone, 1986) or, in the case of D-lactic acid, are excreted unchanged by the kidney. Biocompatible solvents utilized with the system include N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). Safety studies conducted with pharmaceutical-grade solvents provide extensive toxicological profiles that support substantial margins of safety for both the neat solvents and ATRIGEL™ formulations prepared with these solvents (Wilson et al., 1965, Jacob and Wood, 1971, David, 1972, Bartsch et al., 1976, Wells and Digenis, 1988, Shirley et al., 1988, Wells et al., 1992, International Specialty Products, unpublished results).