A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.
A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Yi
Y
Wei
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Yuxia
Y
Wang
Shenyang Agriculture University, Shenyang, Liaoning 110161, People's Republic of China.
Huixia
H
Zhang
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Weiqing
W
Zhou
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China. Electronic address: ghma@home.ipe.ac.cn.
Guanghui
G
Ma
D002116:Calcitonin / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry*; D065546:Drug Liberation; D008863:Microspheres; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D013499:Surface Properties
D004337:Drug Carriers; D010455:Peptides; C028815:salmon calcitonin; D002116:Calcitonin
Narrow size distribution; Porous microspheres; Salmon calcitonin; Sustained release; mPEG-PLGA