Effects of Bovine Serum Albumin and Heparin on the Basic Fibroblast Growth Factor Release from Smart Poly(N-isopropylacrylamide) Nanoparticles for Induction of Angiogenesis in Adult Stem Cells

Background and Aim: Growth factor (GFs) delivery with a certainconcentration and release kinetic is one of the main challenges in tissueengineering. Using controlled spatiotemporal release of the GFs can bean approach to achieve this aim. Poly(N-isopropylacrylamide) (PNIPAM)is the most prominent candidate thermally responsive polymer todeliver the drug due to its sharp transition which is around physiologicaltemperature. The aim of this research was to investigate the basicfibroblast growth factor (bFGF) release from PNIPAM nanoparticles indifferent bFGF loading conditions.Methods: In this study, temperature-sensitive PNIPAM nanoparticleswere first synthesized by free radical polymerization technique.Nanoprecipitation and diffusion methods were studied to load the basicfibroblast growth factor (bFGF) in PNIPAM nanoparticles. According tothe results, the diffusion method is more suitable to load the GFs. Twodifferent formulations of bFGF with and without Bovine Serum Albumin(BSA) and Heparin (Hep) were used to load the bFGF in PNIPAMnanoparticles by the diffusion method. The effects of BSA and Hep on thebFGF release kinetic profile were carefully investigated. BSA and Hepwere used to prevent adsorption to microtube walls and to stabilize theGFs, respectively. The biological evaluation of PNIPAM nanoparticleson human bone marrow stem cells (hBMSCs) was also studied via anindirect method, according to the ISO 10993-5 cytotoxicity standard.Results: Morphology of the PNIPAM nanoparticles before and after thenanoprecipitation process and diffusion method was studied by scanningelectron microscope. The results showed that the nanoprecipitationprocess caused polymer degradation due to using the organic N,NDimethylacetamidesolvent, as a result, the diffusion method is moresuitable to load the GFs. The PNIPAM nanoparticles had spherical grainsin the range of 50–150 nm. The cumulative percentage bFGF releaseafter 72 h for pure bFGF loaded PNIPAM (bFGF-PNIPAM) and bFGFBSA-Hep added loaded PNIPAM (bFBH-PNIPAM) were 100 and 80%,respectively. The presence of BSA and heparin decreased the bFGF burstrelease from bFBH-PNIPAM compare to bFGF-PNIPAM. The biologicalevaluation revealed the particles up to a concentration of 3 mg/mL didnot show any toxicity on hBMSCs.Conclusion: According to the given data the GFs loaded PNIPAMnanoparticles is promising nanosystem that can be applied to deliverthe bioactive GFs for tissue engineering applications. By using heparinand BSA, the bFGF release was better controlled as it had diminishedburst release and more slowly drug release kinetic. Our data showed thePNIPAM NPs have the potential to load and release the angiogenic GFsfor stimulation of angiogenesis in bone tissue engineering.

کلیدواژه ها:

Temperature-sensitive PNIPAM nanoparticles ، Growth factor delivery ، Angiogenesis ، Human bone marrow stem cells (hBMSCs)