Glucose-Responsive Microspheres as a Smart Drug Delivery System for Controlled Release of Insulin. 2020

Jiaojiao Yu, and Qiongyan Wang, and Haofan Liu, and Xiaosong Shan, and Ziyan Pang, and Pengjin Song, and Feng Niu, and Liandong Hu
School of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, No. 180, Wusi East Road, Baoding, 071000, Hebei, China.

OBJECTIVE 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.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297 Male Males
D008863 Microspheres Small uniformly-sized spherical particles, of micrometer dimensions, frequently labeled with radioisotopes or various reagents acting as tags or markers. Latex Beads,Latex Particles,Latex Spheres,Microbeads,Bead, Latex,Beads, Latex,Latex Bead,Latex Particle,Latex Sphere,Microbead,Microsphere,Particle, Latex,Particles, Latex,Sphere, Latex,Spheres, Latex
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier

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