Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.
The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system.
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Fei
F
Yu
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Yang
Y
Li
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Chang Sheng
CS
Liu
Department of Pharmacy, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
Qin
Q
Chen
The Third Hospital of Yanzhou Mining Group, Jining 272100, China.
Gui Huan
GH
Wang
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Wei
W
Guo
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China. Electronic address: xewu@xmu.edu.cn.
Xue E
XE
Wu
Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China. Electronic address: lidh@xmu.edu.cn.
Dong Hui
DH
Li
Suzhou Key Lab of Green Chemical Engineering, School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China. Electronic address: duo.wu@suda.edu.cn.
Winston Duo
WD
Wu
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China; Suzhou Key Lab of Green Chemical Engineering, School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China. Electronic address: xdchen@suda.edu.cn.
Xiao Dong
XD
Chen
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018938:Caco-2 Cells; D002214:Capsules; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008055:Lipids; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011098:Polyglactin 910 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013608:Tablets, Enteric-Coated
D001786:Blood Glucose; D002214:Capsules; D003692:Delayed-Action Preparations; D007328:Insulin; D008055:Lipids; D013608:Tablets, Enteric-Coated; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols
Capsule; Insulin; Micro-particles; Monodisperse; Oral