Jiaojiao Yu1,2,3, Qiongyan Wang1, Haofan Liu1, Xiaosong Shan2, Ziyan Pang3, Pengjin Song1, Feng Niu4, Liandong Hu5,6. 1. School of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, No. 180, Wusi East Road, Baoding, 071000, Hebei, China. 2. Affiliated Hospital of Hebei University, Baoding, 071000, China. 3. Xingtai Third Hospital, Xingtai, 054000, China. 4. NBP Pharmaceutical Company Limited, CSPC Pharmaceutical Group Limited, Shijiazhuang, 052165, China. 5. School of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, No. 180, Wusi East Road, Baoding, 071000, Hebei, China. gz1205@126.com. 6. Affiliated Hospital of Hebei University, Baoding, 071000, China. gz1205@126.com.
Abstract
BACKGROUND AND OBJECTIVES: Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy. METHODS: In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier. RESULTS: The microspheres had a good spherical structure with a particle size of 5 ~ 10 μm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating. CONCLUSIONS: The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.
BACKGROUND AND OBJECTIVES:Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy. METHODS: In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier. RESULTS: The microspheres had a good spherical structure with a particle size of 5 ~ 10 μm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating. CONCLUSIONS: The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.
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