A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery

Artif Cells Nanomed Biotechnol. 2018 Feb;46(1):169-177. doi: 10.1080/21691401.2017.1304403. Epub 2017 Apr 4.


This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG-2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer-Peppas' model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy.

Keywords: Cationic liposome; drug release kinetics; mathematical modelling; siRNA delivery; thermo and pH sensitivity.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Liberation*
  • Humans
  • Kinetics
  • Liposomes / chemistry*
  • Models, Chemical*
  • Nanostructures / chemistry*
  • Polyethylene Glycols / chemistry*
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / genetics
  • Transfection


  • Drug Carriers
  • Liposomes
  • RNA, Small Interfering
  • Polyethylene Glycols
  • Doxorubicin