Investigation of 1,2-Dimyristoyl-sn-Glycero-3-Phosphoglycerol-Sodium (DMPG-Na) Lipid with Various Metal Cations in Nanocochleate Preformulation: Application for Andrographolide Oral Delivery in Cancer Therapy

• Published in: AAPS PharmSciTech Vol. 21; no. 7; p. 279
• Main Authors: Ahiwale, Raj J., Chellampillai, Bothiraja, Pawar, Atmaram P.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 09.10.2020
• Subjects: Administration, Oral; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning; Cations; Diterpenes - administration & dosage; Diterpenes - pharmacokinetics; Diterpenes - therapeutic use; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Female; Humans; Nanoparticles - chemistry; Neoplasms - drug therapy; Particle Size; Pharmacology/Toxicology; Pharmacy; Phosphatidylglycerols - chemistry; Rats; Rats, Wistar; Research Article; Sodium; Solubility; Tissue Distribution; DMPG-Na; nanocochleates; cancer; pharmacokinetic; preformulation; andrographolide; tissue distribution
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-020-01801-1

This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl 2 (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats. Nanocochleates developed with CaCl 2 had a significant reduction in PS (1.78-fold) and ZP (1.38-fold), and elevation of EE (1.17-fold) as compared to AlCl 3 developed NCs. Trivalent ions demonstrated elevation of TT as compared to divalent ions. Spiral-shaped ANDNCs demonstrated ZP, PS, and EE of − 121.46 ± 15.12 mV, 360 ± 47 nm, and 68.12 ± 3.81% respectively. In vitro release study of ANDNCs showed a strong pH-dependent release profile due to hydrogen bonding between NCs and andrographolide (AND). Formulated ANDNCs demonstrated 26.99-fold decrease in IC50 value as compared to free AND. Additionally, the oral bioavailability of AND from ANDNCs improved by 1.81-fold as compared to free AND. Furthermore, ANDNCs showed minimum accumulation within the vital organs such as liver, kidney, and spleen. Briefly, the preformulation study laid a platform for better understanding the NCs and its components. Further, developed ANDNCs revealed superior physiochemical properties to be used as an alternative for a clinical setting.