Nanostructured lipid carrier-loaded metformin hydrochloride: Design, optimization, characterization, assessment of cytotoxicity and ROS evaluation

• Published in: Chemistry and physics of lipids 2023-01, Vol.250, p.105256, Article 105256
• Main Authors: Shete, Meghanath B., Deshpande, Ashwini S., Shende, Pravin K.
• Format: Article
• Language: English
• Subjects: Apoptosis; cell death; cytotoxicity; diabetes; Drug Carriers; emulsifying; Humans; hydrophilicity; KB cells; Lipids; Metformin; Metformin - pharmacology; Mouth Neoplasms; Nanostructured lipid carrier; Nanostructures; Oral cancer; Particle Size; physics; Reactive Oxygen Species; sonication; surfactants
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2022.105256

Metformin hydrochloride (MET) is commonly used in diabetes treatment. Recently, it has gained interest for its anticancer potential against a wide range of cancers. Owing to its hydrophilic nature, the delivery and clinical actions of MET are limited. Therefore, the present work aims to develop MET-encapsulated NLCs using the hot-melt emulsification and probe-sonication method. The optimization was accomplished by 33 BB design wherein lipid ratio, surfactant concentration, and sonication time were independent variables while the PS (nm), PDI, and EE (%) were dependent variables. The PS, PDI, % EE and ZP of optimized GMSMET-NLCs were found to be 114.9 ± 1.32 nm, 0.268 ± 0.04 %, 60.10 ± 2.23 %, and ZP − 15.76 mV, respectively. The morphological features, DSC and PXRD, and FTIR analyses suggested the confirmation of formation of the NLCs. Besides, optimized GMSMET-NLCs showed up to 88 % MET release in 24 h. Moreover, GMSMET-NLCs showed significant cell cytotoxicity against KB oral cancer cells compared with MET solution as shown by the reduction of IC50 values. Additionally, GMSMET-NLCs displayed significantly increased intracellular ROS levels suggesting the GMSMET-NLCs induced cell death in KB cells. GMSMET-NLCs can therefore be explored to deliver MET through different routes of administration for the effective treatment of oral cancer. [Display omitted] •Glyceryl monostearate-based MET-NLCs were prepared using the hot-melt emulsification and sonication method.•GMSMET-NLCs were optimized using the Box-Behnken design.•Characterization of GMSMET-NLCs performed by FTIR, DSC, XRD, and SEM studies.•GMSMET-NLCs showed sustained release.•GMSME-NLCs demonstrated significant cytotoxicity and increased ROS levels in KB cells caused to induction of apoptosis.