Coadministration of Polypeptide-k and Curcumin Through Solid Self-Nanoemulsifying Drug Delivery System for Better Therapeutic Effect Against Diabetes Mellitus: Formulation, Optimization, Biopharmaceutical Characterization, and Pharmacodynamic Assessment

Assay Drug Dev Technol. 2019 May/Jun;17(4):201-221. doi: 10.1089/adt.2018.902. Epub 2019 May 17.

Abstract

An attempt has been made to prepare solid self-nanoemulsifying drug delivery system (SNEDDS) of polypeptide-k (PPK) and curcumin (CRM) using Labrafil M1944 CS as oil, Tween-80 as surfactant, Transcutol P as cosurfactant and Aerosil-200 (A-200) as porous hydrophobic carrier for improving their antidiabetic potential through oral delivery. Box-Behnken Design was used to optimize the liquid formulation based on the results of the mean droplet size, polydispersity index, percentage drug loading, and zeta potential. The formulation was adsorbed on Aerosil-200 through spray drying. The formulation showed desirable micromeritic, disintegration, and dissolution properties. About fivefold rise in the dissolution and permeation rate for drugs was observed from formulations vis a vis their unprocessed forms. The formulation was found to be stable with variation in pH, dilution, and temperature. The individual solid SNEDDS formulation of PPK and CRM and their combination were evaluated for antidiabetic potential and the results were compared with their naive forms on streptozotocin-induced diabetic rats. The results revealed better control of serum glucose level and other biochemical tests, such as liver parameters, lipid profiles, and antioxidant levels, as well as histological evaluation of pancreatic tissues in all the solid SNEDDS formulation as compared with their naive forms.

Keywords: diabetes; diffusion; dissolution; solid SNEDDS; spray drying; streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Curcumin* / administration & dosage
  • Curcumin* / pharmacokinetics
  • Curcumin* / therapeutic use
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Drug Compounding
  • Drug Delivery Systems*
  • Emulsions / chemistry
  • Hydrogen-Ion Concentration
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / pharmacokinetics
  • Hypoglycemic Agents* / therapeutic use
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptides* / administration & dosage
  • Peptides* / pharmacokinetics
  • Peptides* / therapeutic use
  • Rats
  • Solubility
  • Streptozocin
  • Surface Properties
  • Tablets
  • Thermodynamics

Substances

  • Emulsions
  • Hypoglycemic Agents
  • Peptides
  • Tablets
  • Streptozocin
  • Curcumin