Development and in vitro evaluation of (β-cyclodextrin-g-methacrylic acid)/Na+-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin

Int J Nanomedicine. 2019 Jul 17:14:5397-5413. doi: 10.2147/IJN.S209662. eCollection 2019.

Abstract

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage. It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible β-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: β-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using β-CD as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing β-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.

Keywords: antihyperlipidemic and toxicity; lovastatin; montmorillonite; nanocomposite networks.

MeSH terms

  • Acrylamides / chemistry
  • Administration, Oral
  • Animals
  • Bentonite / chemistry*
  • Calorimetry, Differential Scanning
  • Delayed-Action Preparations
  • Drug Liberation
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lipids / blood
  • Lovastatin / administration & dosage*
  • Methacrylates / chemistry*
  • Nanocomposites / chemistry*
  • Nanocomposites / ultrastructure
  • Organ Specificity
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Temperature
  • Tensile Strength
  • Thermogravimetry
  • Toxicity Tests, Acute
  • X-Ray Diffraction
  • beta-Cyclodextrins / chemistry*

Substances

  • Acrylamides
  • Delayed-Action Preparations
  • Hydrogels
  • Lipids
  • Methacrylates
  • beta-Cyclodextrins
  • Bentonite
  • methacrylic acid
  • Lovastatin
  • N,N'-methylenebisacrylamide
  • betadex