Investigation of different types of nano drug delivery systems of atorvastatin for the treatment of hyperlipidemia

Drug Dev Ind Pharm. 2018 Dec;44(12):2048-2060. doi: 10.1080/03639045.2018.1508225. Epub 2018 Sep 7.

Abstract

Different nanoparticles, namely solid lipid nanoparticles, nanocrystals and nanosponges loaded with atorvastatin were successfully fabricated with desirable technological properties which reckoned promising methods of their preparation. Further, suitable characterization and evaluation parameters for in-vitro and in-vivo studies were conducted which led to increase in drug's bioavailability, provided better in-vivo efficacy and reduced toxicity in treating hyperlipidemia systemically. Particle sizes were found to be less than 300 nm with minimal polydispersity indices and maximized entrapment efficiency which are pre-requisites for their absorption in intestines. Drug release studies showed sustained release for a prolonged period, which was justified by release kinetics. Augmented bioavailability and reduced lipoprotein levels were key observations. In addition, reduced hepatotoxicty, decreased myotoxicity and diminished drug distribution were also the important highlights of these developed nanosystems as compared with the pure drug and marketed formulation. Histopathology of liver confirmed reduced hepatotoxicity. An elaborate comparison of these nanoparticles along with pure drug and marketed formulation concluded that nanosponges are potentially one of the best nanosystems for treating hyperlipidemia by systemic delivery.

Keywords: Solid lipid nanoparticles; atorvastatin; bioavailability; hyperlipidemia; nanocrystals; nanosponges.

MeSH terms

  • Administration, Oral
  • Animals
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / pharmacokinetics
  • Atorvastatin / administration & dosage*
  • Atorvastatin / chemistry
  • Atorvastatin / pharmacokinetics
  • Biological Availability
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Drug Compounding / methods*
  • Drug Liberation
  • Humans
  • Hyperlipidemias / blood
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / etiology
  • Hyperlipidemias / pathology
  • Lipids / chemistry
  • Lipoproteins / blood
  • Liver / drug effects
  • Liver / pathology
  • Nanoparticles / chemistry*
  • Rats
  • Rats, Wistar

Substances

  • Anticholesteremic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • Lipoproteins
  • Atorvastatin