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Abstract
Polymeric microparticles with covalently attached biotin are proposed as versatile targeting vehicles for drug delivery. The proposed microparticles made of 85/15 poly (lactic-co-glycolic acid) (PLGA) will have biotin available on the outside of the particle for the further attachment with an avidin group. Taking advantage of biotin’s high affinity for avidin, and avidin’s well-known chemistry, the particle has the potential to be easily coated with a variety of targeting moieties. This paper focuses on the design and resulting effect of adding biotin to PLGA microparticles using an integrated experimental and modeling approach. A fluorescent-tagged avidin (488-streptavidin) was used to confirm the presence and bioavailability of biotin on the outside of the particles. For the purpose of this study, bovine serum albumin (BSA) was used as a model therapeutic drug. Microparticles were created using two different types of polyvinyl alcohol 88 and 98 mol% hydrolyzed, which were then analyzed for their size, morphology, and encapsulation capacity of BSA. Release studies performed in vitro confirmed the slow release of the BSA over a 28-day period. Based on these release profiles, a release kinetics model was used to further quantify the effect of biotinylation of PLGA microparticles on their release characteristics by quantitatively extracting the effective drug diffusivity and drug desorption rate from the release profiles. It was found that the biotinylation of the PLGA microparticles slowed down both the drug desorption and drug diffusion process, which confirmed that biotinylated PLGA microparticles can be used for controlled drug release. The presented technology, as well as the proposed integrated experimental and modeling approach, forms a solid foundation for future studies using a cell-specific ligand that can be attached to avidin and incorporated onto the microparticles for targeted delivery.Electronic supplementary materialThe online version of this article (doi:10.1186/2194-0517-2-3) contains supplementary material, which is available to authorized users.
Highlights
Polymeric microparticles have been widely researched for their ability to serve as controlled drug delivery vehicles Brannon-Peppas (1995; Cleland 1997; Shive and Anderson 1997)
The primary goal of this paper is to evaluate the effect of the biotinylation of the poly(lactic-co-glycolic acid) (PLGA) microparticles on their morphology and release characteristics
Presence of green fluorophore around the microparticle indicates that the biotin attached to the perimeter, and was still biologically available for the streptavidin post-microparticle processing
Summary
Polymeric microparticles have been widely researched for their ability to serve as controlled drug delivery vehicles Brannon-Peppas (1995; Cleland 1997; Shive and Anderson 1997). The new goal in these designs, is to take them a step further and incorporate a method for targeting specific cells Brannon-Peppas and Blanchette (2004; Fung and Saltzman 1997). A method to target these cells directly would increase the potency of the drugs, and drastically improve the quality of life for the patients on these treatments. While biodegradable polymeric microparticles have been investigated for the controlled release of anticancer therapeutics Fung and Saltzman (1997; Datta et al 2006; Folger et al 2006), and to a limited extent, for antiviral drugs Datta et al (2006), the challenge of effective targeting still remains. With an evolving field of possible targets and ligands, the challenge for the engineers is to create a robust mechanism for incorporation of these new ligands to a polymeric delivery vehicle
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