Optimization and evaluation of Oridonin-loaded Soluplus®-Pluronic P105 mixed micelles for oral administration

Int J Pharm. 2017 Feb 25;518(1-2):193-202. doi: 10.1016/j.ijpharm.2016.12.047. Epub 2016 Dec 22.

Abstract

In this study, a new type of mixed micelles was developed using Soluplus® (SOL) and Pluronic® P105 (P105) for the encapsulation of Oridonin (ORN). Oridonin-loaded micelles (ORN-M) were simply prepared using solvent evaporation and characterized for particle size, particle morphology, encapsulation efficiency, and drug loading. In addition, the in vitro drug release behavior of ORN-M was assessed using the widely applied dialysis bag technique. The pharmacokinetic property of ORN was explored in rats after oral administration of ORN-M. Optimized ORN-M were of a small size (137.2±1.65nm) and spherical shape when the ratio of SOL:P105 was 3:1, with entrapment efficiency 90.48±1.85% and drug loading 15.08±0.38%. Oral absorption capacity of ORN was greatly enhanced with a relative bioavailability of 210.55% in comparison to that of in-house suspensions, which suggests that ORN-M shows significantly improved bioavailability and drug absorption characteristics. Overall, the optimized SOL-P105 dual mixed micelles show great potential for use as oral drug carriers for cancer treatment.

Keywords: Bioavailability; Micelles; Oridonin; Pluronic(®) P105; Soluplus(®).

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic* / administration & dosage
  • Antineoplastic Agents, Phytogenic* / chemistry
  • Antineoplastic Agents, Phytogenic* / pharmacokinetics
  • Biological Availability
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes, Kaurane* / administration & dosage
  • Diterpenes, Kaurane* / chemistry
  • Diterpenes, Kaurane* / pharmacokinetics
  • Drug Carriers* / administration & dosage
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Liberation
  • Humans
  • Male
  • Mice, Nude
  • Micelles*
  • Particle Size
  • Poloxamer* / administration & dosage
  • Poloxamer* / chemistry
  • Poloxamer* / pharmacokinetics
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / chemistry
  • Polyethylene Glycols* / pharmacokinetics
  • Polyvinyls* / administration & dosage
  • Polyvinyls* / chemistry
  • Polyvinyls* / pharmacokinetics
  • Rats, Sprague-Dawley
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes, Kaurane
  • Drug Carriers
  • Micelles
  • Polyvinyls
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • oridonin
  • Poloxamer
  • Polyethylene Glycols
  • pluronic P105