Synthetic degradable polymers are commonly used for drug delivery and to aid in tissue regeneration. Drugs are routinely encapsulated in the material for subsequent diffusion- and/or degradation-mediated release. Limitations with encapsulation, however, include limited payload and the potential for premature exhaustion of the delivery system. To prolong release, drugs have been conjugated to polymers. Drug can be attached to the polymer via a linker that subsequently releases the molecule following cleavage, or it can be incorporated into the polymeric backbone during synthesis. The overarching goal of this project is to develop and characterize a polymer synthesized using drug molecules, in the present case simvastatin, as monomers. The working hypothesis is that the structure of simvastatin, with a lactone moiety in the prodrug, is amenable to ring-opening polymerization. As such, polymerized simvastatin could then be processed into films that degrade by hydrolysis to release bioactive simvastatin molecules, which have osteogenic, anti-inflammatory, and angiogenic properties in addition to their well-known known hypolipidemic effects.
Aim 1 will develop and characterize a degradable, polymerized form of simvastatin. With respect to this objective, it is hypothesized that the polymer can be processed into biodegradable films that release simvastatin.
Aim 2 will investigate whether polymerized films of simvastatin degrade in vivo to stimulate osteogenesis in a rodent supracalvarial implantation model. It is hypothesized that, as the polymer degrades, bioactive simvastatin is released to enhance local bone formation. If the proof-of-principle studies proposed for this Exploratory/Developmental Award are successful, the polymer may be fabricated into a variety of physical forms (e.g., microspheres and tissue engineering scaffolds) to exploit the pleiotropic effects of simvastatin for bone and other tissue applications, as well as the methods potentially being applicable to other members of the statin family.

Public Health Relevance

Synthetic degradable polymers are commonly employed for drug delivery and to aid in tissue regeneration. Although current materials are useful, limitations include limited payload and instability of drug. This project will develop a polymer directly composed of the drug simvastatin, which has several important biological activities, including osteogenic, anti-inflammatory, and angiogenic effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB017902-01
Application #
8622285
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Tucker, Jessica
Project Start
2014-09-22
Project End
2016-06-30
Budget Start
2014-09-22
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$186,334
Indirect Cost
$61,334
Name
University of Kentucky
Department
Biomedical Engineering
Type
Other Domestic Higher Education
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Asafo-Adjei, Theodora A; Dziubla, Thomas D; Puleo, David A (2014) Synthesis and Characterization of a Poly(ethylene glycol)-Poly(simvastatin) Diblock Copolymer. RSC Adv 4:58287-58298