Injectable controlled release depots for large molecules

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable...

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Bibliographic Details
Published in:Journal of controlled release Vol. 190; pp. 240 - 253
Main Authors: Schwendeman, Steven P., Shah, Ronak B., Bailey, Brittany A., Schwendeman, Anna S.
Format: Journal Article
Language:English
Published: Netherlands 28.09.2014
Subjects:
biocompatible materials
Biocompatible Materials - administration & dosage
biodegradability
children
Delayed-Action Preparations - administration & dosage
Drug Carriers
Drug Compounding
drug delivery systems
drug formulations
drugs
encapsulation
Humans
Injections
Lactic Acid
Macromolecular Substances - administration & dosage
peptides
Pharmacokinetics
Polyglycolic Acid
Polylactic Acid-Polyglycolic Acid Copolymer
Polymers
proteins
United States
United States
Depot
Biodegradable
PLGA
Peptide
Controlled release
Protein
ISSN:0168-3659, 1873-4995, 1873-4995
Online Access:Get full text
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Summary:Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few "real world" biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LARproducts, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.
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ISSN:0168-3659
1873-4995
1873-4995
DOI:10.1016/j.jconrel.2014.05.057