NDLI: Osmotic-Driven Release Kinetics of Bioactive Therapeutic Proteins from a Biodegradable Elastomer are Linear, Constant, Similar, and Adjustable

Content Provider	Springer Nature Link
Author	Gu, Frank Neufeld, Ronald Amsden, Brian
Copyright Year	2006
Abstract	The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2) were embedded in the device as sample therapeutic proteins, and their release and bioactivity were compared to that achieved previously with interferon-γ (IFN-γ).A photo-cross-linkable biodegradable macromer consisting of acrylated star(ɛ-caprolactone-co-d,l-lactide) was prepared. VEGF, IL-2, and IFN-γ were co-lyophilized with serum albumin and trehalose at different ratios and were then embedded into the elastomer by photo-cross-linking the lyophilized particles in a macromer solution. The protein mass and the bioactivity in the release supernatant were measured by enzyme-linked immunosorbent and cell-based assays.VEGF, IL-2, and IFN-γ were released at the same, nearly constant rate of 25.4 ng/day for over 18 days. Using the optimum elastomer formulation, the release profiles of the proteins were essentially identical, and their rates were linear and constant. Cell-based bioactivity assays showed that 70 and 88% of the released VEGF and IL-2, respectively, were bioactive. The rate of protein release can be adjusted by changing the trehalose loading concentration in the elastomer matrix without altering the linear nature of the protein release kinetics. The elastomeric device degraded in PBS buffer within 85 days.The elastomer formulation shows promising potential as a sustained protein drug delivery vehicle for local delivery applications.
Starting Page	782
Ending Page	789
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	4
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-03-24
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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