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

Abstract

Asif Mahmood,1,2 Amara Sharif,2 Faqir Muhammad,2 Rai Muhammad Sarfraz,3 Muhammad Asad Abrar,4 Muhammad Naeem Qaisar,3 Naveed Anwer,5 Muhammad Wahab Amjad,6 Muhammad Zaman11Department of Pharmaceutics, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan; 2Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad, Pakistan; 3Department of Pharmaceutics, College of Pharmacy, University of Sargodha, Sargodha, Pakistan; 4Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan; 5Saulat Institute of Pharmaceutical Sciences, Quaid-I-Azam University, Islamabad, Pakistan; 6Faculty of Pharmacy, Northern Border University, Arar, Saudia ArabiaBackground: 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: lovastatin, nanocomposite networks, montmorillonite, antihyperlipidemic and toxicity

Keywords

• Lovastatin
• Nanocomposite networks
• Montmorillonite
• Antihyperlipidemic and Toxicity.