Amphiphilic PHA-mPEG copolymeric nanocontainers for drug delivery: preparation, characterization and in vitro evaluation.
Amphiphilic biodegradable core-shell nanoparticles were prepared by emulsification-solvent evaporation technique from diblock copolymers which were synthesized by chemical coupling of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) P(3HB-co-4HB) to monomethoxy poly(ethylene glycol) (mPEG) through transesterification reaction. The nanoparticles were found to be assembled in aqueous solution into an outer hydrophilic shell of mPEG connected to the interior hydrophobic polyhydroxyalkanoate (PHA) copolymer core, which was identified by a comparative analysis of enzymatic degradation of the mPEG-coupled and non-coupled PHA nanoparticles. Morphological examination under atomic force microscope showed the formation of smooth spherically shaped nanoparticles. The average particle sizes and zeta potentials of amphiphilic nanoparticles were in the range of 112-162 nm and -18 to -27 mV, respectively. A hydrophobic drug thymoquinone was encapsulated in the nanoparticles and its release kinetics was studied. The in vitro cytotoxicity evaluation of the nanoparticles on prenatal rat neuronal hippocampal and fibroblast cells revealed that biocompatibility of the amphiphilic nanoparticles was generally independent of the ratio of comonomer units in the PHA block. In conclusion, the amphiphilic nanoparticles contained the hydrophobic PHA segments buried in the core and could thus be used as safe carriers for the controlled release of variety of hydrophobic drugs.
Shah
Mohsin
M
Nano-Biomaterials Science Laboratory, Division of Applied Life Sciences (BK21), Graduate School and Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Naseer
Muhammad Imran
MI
Choi
Mun Hwan
MH
Kim
Myeong Ok
MO
Yoon
Sung Chul
SC
D016475:3T3 Cells; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry; D018929:Cell Culture Techniques; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D051379:Mice; D053758:Nanoparticles; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D054813:Polyhydroxyalkanoates / Q000737:chemistry*; D051381:Rats; D012996:Solutions
D016227:Benzoquinones; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D054813:Polyhydroxyalkanoates; D012996:Solutions; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C003466:thymoquinone