title: Novel PLGA-based nanoparticles for the oral delivery of insulin.
abstract: BACKGROUND
  Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS).
  
  
  OBJECTIVE
  To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin.
  
  
  METHODS
  A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water-oil-water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.
  
  
  RESULTS
  The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6% ± 1.2%, and the mean diameter of the NPs was 180 ± 20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects.
  
  
  CONCLUSIONS
  ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.
authors.affiliation: Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India.
authors.forename: Sampath
authors.initials: S
authors.lastname: Malathi
authors.affiliation: Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Nandhakumar
authors.affiliation: Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India.
authors.forename: Velayudham
authors.initials: V
authors.lastname: Pandiyan
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
authors.affiliation: Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India.
authors.forename: Sengottuvelan
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D007328:Insulin; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D024502:alpha-Tocopherol; D005947:Glucose; C014225:tocophersolan
keywords: drug delivery; histopathology; hypoglycemic effect; poly(ethylene glycol); polymer nanoparticles; tocopherol poly(ethylene glycol) 1000 succinate
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