ABSTRACT
The present study investigated the release profiles of insulin from Pluronic F-127 (PF-127) gel containing unsaturated fatty acids such as oleic acid (18:1), eicosapentaenoic acid (20:5) or docosahexaenoic acid (22:6) and the hypoglycemic effect of insulin following the buccal administration of the gel formulations in normal rats. Insulin release from the gels decreased in the presence of unsaturated fatty acids. Remarkable and continuous hypoglycemia was induced by all PF-127 gels (insulin dose, 25 IU/kg) containing unsaturated fatty acids. PF-127 gels containing oleic acid showed the highest pharmacological availability (15.9+/-7.9%). Our finding demonstrate that 20% PF-127 gels containing unsaturated fatty acids are potential formulations for the buccal delivery of insulin.
Subject(s)
Fatty Acids, Unsaturated/administration & dosage , Insulin/administration & dosage , Mouth Mucosa/metabolism , Poloxamer/administration & dosage , Surface-Active Agents/administration & dosage , Animals , Cheek , Gels , Insulin/chemistry , Insulin/pharmacokinetics , Male , Rats , Rats, WistarABSTRACT
The main objective of this work was to evaluate the use of Pluronic (PF127) gels, polylactic-co-glycolic acid (PLGA) nanoparticles and their combination for parenteral delivery of peptides and proteins having short half-lives using insulin as a model drug. The in vitro insulin release profiles of various PF127 formulations were evaluated at 37 degrees C using a membraneless in vitro model. In vivo evaluation of the serum glucose and insulin levels was performed following subcutaneous administration of various insulin formulations in normal rats. The in vitro results demonstrated that the higher the concentration of PF127 in the gel, the slower the release of insulin from the matrices, independent of the vehicle used. The acute hypoglycemic peak resulting from administration of an insulin solution between 0.5 and 2.0 h after administration (peak at 1 h) is replaced after administration of insulin-PLGA nanoparticles by an almost constant hypoglycemic effect with a slower recovery of the serum glucose levels at about 2 h after administration. By loading insulin into PF127 gels, a slower and more prolonged hypoglycemic effect of insulin was obtained in inverse proportion to the polymer concentration. PF127 gel formulations containing insulin-PLGA nanoparticles had the most long-lasting hypoglycemic effects of all formulations. From the current in vitro and in vivo study, we concluded that PF127 gel formulations containing either drug or drug-nanoparticles could be useful for the preparation of a controlled delivery system for peptides and proteins having short half-lives.
Subject(s)
Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Poloxamer , Animals , Blood Glucose/metabolism , Excipients , Gels , Hypoglycemic Agents/pharmacology , Injections, Subcutaneous , Insulin/pharmacology , Lactic Acid , Male , Microspheres , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Rats , Rats, Wistar , Skin Absorption , SolutionsABSTRACT
The objective of this study was to prepare and to evaluate Pluronic F-127 (PF127) gel containing unsaturated fatty acids such as oleic acid (18:1), eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) as a potential formulation for rectal delivery of insulin. The hypoglycemic effect of insulin was examined following rectal administration of the various formulations in normal rats. Rectal insulin absorption was markedly enhanced, and marked hypoglycemia was induced by all PF127 gels (insulin dose, 5 U/kg) containing different unsaturated fatty acids. PF127 gels containing unsaturated fatty acids presented low tmax mean values indicating that the absorption of insulin occurred very rapidly in the rectum. The relative hypoglycemic efficacy of PF127 gel formulations containing fatty acids such as oleic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) were 28.4+/-8.1, 26.8+/-14.3 and 23.1+/-5.7%, respectively. The finding demonstrated that 20% PF127 gels containing unsaturated fatty acids are potential formulations for rectal delivery of insulin.
Subject(s)
Insulin/administration & dosage , Insulin/pharmacokinetics , Poloxamer/chemistry , Administration, Rectal , Animals , Biological Availability , Chemistry, Pharmaceutical , Docosahexaenoic Acids/chemistry , Eicosapentaenoic Acid/chemistry , Fatty Acids, Unsaturated/chemistry , Gels , Hypoglycemia/chemically induced , Insulin/blood , Male , Oleic Acid/chemistry , Rats , Rats, WistarABSTRACT
The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation-solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160-170 nm, except for insulin nanoparticles, which showed a smaller particle size. The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles. In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicity. More hydrophilic drugs, such as vancomycin and phenobarbital, were poorly encapsulated in PLGA nanoparticles. Insulin was preferentially surface bound on the PLGA nanoparticles. However, a strong hypoglycemic effect of the insulin was observed after administration of the suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of male Wistar rats.
