The Preparation And Property Of Biotin Modified Poly (Lactic Acid)-A Potential Targeted Drug Carrier

The research work is on the basis of my predecessor in our laboratory. Firstly, Poly (ethylene glycol) (PEG)-modified Poly (lactic acid) (PPLA) was synthesized by grafting PEG onto MPLA. Then, in order to develop biomaterial which may be used in targeted drug delivery system, a biotinylated PLA (BPLA) was obtained by covalently grafting PPLA with biotin as raw material to synthesize a new polymer which may lead to potential applications in drug delivery system.As a new polymer, BPLA was made to be nanopaticles (NPs) by self-assembled in aqueous medium without naproxen to test its performance. Then we studied its drug loading properties when encapsulated with naproxen and targeting properties in vitro when we simulated the static and dynamic state of body fluid. Ultimately, we tested the biocompatibility by hemolysis test to prepare for potential application in vivo.The main contents of this research are shown below:(1) PPLA was synthesized by grafting H₂N-PEG-NH₂ onto MPLA and characterized its structure by Ninhydrin Coloration and Hydrogen Nuclear Magnetic Resonance (1H-NMR).(2) Using Dicyclohexylcarbodiimide (DCC) as a condenser, BPLA was prepared by Biotin N-hydroxysuccinimide ester (BNHS) to graft biotin onto PPLA. The product BPLA was characterized by Ninhydrin Coloration and 1H-NMR. The results indicated that biotin had successfully covalently grafted onto PPLA.(3) BPLA NPs was made by self-assembled in aqueous medium without naproxen to test its performance. The critical micelle concentration (CMC) of BPLA was 7.1×10-4mg/mL which was detected by fluorospectrophotometer and the result indicated its good heat stabilization. Analyzed by Transmission Electron Microscopy (TEM), the morphology of BPLA NPs was spherical and well separated. the size particle was about 200nm. The Dynamic Light Scattering (DLS) tests revealed that the zeta potential was -37.56mV, the particle size and size dispersion (PDI) were 161.6nm and 0.117 just after BPLA NPs was prepared; the zeta potential was -41.14mV, the particle size and PDI were 144.3nm and 0.138 after 30 days standing. It indicated that the BPLA NPs was stable at room temperature.(4) With hydrophobic naproxen as model drug, we prepared drug-loaded BPLA/naproxen NPs by solvent evaporation method. Analyzed by TEM, the morphology of BPLA/naproxen NPs was spherical and well separated. The particle size had increased after encapsulated of naproxen tested by DLS and the results also indicated that BPLA/naproxen NPs were stable after diluting with phosphate buffer solution (PBS) or changing the solution acidalcaline (PH). The naproxen entrapment efficiency (EE) was 51.88% and the release results showed that BPLA/naproxen NPs could stably release drug up to 7 days in PBS at 37℃and may be a drug delivery carrier for hydrophobic drug.(5) On the simulating static and dynamic state of liquid in vitro to test the targeting properties of BPLA NPs. The results showed BPLA NPs were able to combine with avidin and also can combine with biotin with the help of avidin. It proved that BPLA NPs had the potential to be a targeted drug delivery carrier. On the other hand, the hemolysis test indicated that hemolysis rate of BPLA NPs without or with naproxen were much lower than the national standard and suggested BPLA NPs were non-urgent toxic and biocompatible.