Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer

Abstract

This study aimed at developing metformin hydrochloride (Met) encapsulated liposomal vesicles for enhanced therapeutic outcomes at reduced doses against breast cancer. Liposomal Met was prepared using thin-film hydration through various loading methods; passive loading, active loading, and drug-loaded lipid film. The drug-loaded film method exhibited maximum entrapment efficiency (~65%) as compared to active loading (~25%) and passive loading (~5%) prepared Met-loaded liposomes. The therapeutic efficacy of these optimized liposomes was evaluated for cellular uptake, cytotoxicity, inhibition of metastatic activity, and apoptosis-inducing activity. Results demonstrated significantly superior activity of positively charged liposomes resulting in reduced IC50 values, minimal cell migration activity, reduced colony formation, and profound apoptosis-induced activity in breast cancer cells as compared to Met. The anti-tumor activity was investigated using a clinically relevant in vitro tumor simulation model, which confirmed enhanced anti-tumorigenic property of liposomal Met over Met itself. To the authors’ knowledge, this is the first report of Met-loaded liposomes for improving the efficacy and therapeutic effect of Met against breast cancer. With the results obtained, it can be speculated that liposomal encapsulation of metformin offers a potentially promising and convenient approach for enhanced efficacy and bioavailability in breast cancer treatment.

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

“…3D spheroid culture methods provide a way to evaluate a drug candidate ex-vivo while mimicking the in-vivo appearance and behavior of tumor mass. We recently described the capability of spheroid cell culture studies to mimic the in-vivo features of tumors [39]. This spheroid study was conducted utilizing two kinds of models, prophylactic and therapeutic, which differ significantly in tumor growth and treatment strategies.…”

Emerging nanoparticulate drug delivery systems of metformin

“…In recent years, a variety of MET-encapsulated nanocarriers have been developed for anticancer therapy, including liposomes, nanomicelles, polymeric NPs and inorganic NPs. Among them, MET-encapsulated liposomal vesicles were widely investigated (Lee et al 2020;Magdy et al 2017;Osama et al 2019;Shukla et al 2019). For instance, Shukla et al prepared MET-encapsulated liposomes with enhanced therapeutic efficacy against breast cancer (Shukla et al 2019).…”

“…Among them, MET-encapsulated liposomal vesicles were widely investigated (Lee et al 2020;Magdy et al 2017;Osama et al 2019;Shukla et al 2019). For instance, Shukla et al prepared MET-encapsulated liposomes with enhanced therapeutic efficacy against breast cancer (Shukla et al 2019). Thin-film hydration method was utilized to prepare the liposomes (Shukla et al 2019).…”

“…For instance, Shukla et al prepared MET-encapsulated liposomes with enhanced therapeutic efficacy against breast cancer (Shukla et al 2019). Thin-film hydration method was utilized to prepare the liposomes (Shukla et al 2019). Three drug loading methods were used to encapsulate MET, including passive loading, active loading, and drug-loaded lipid film (Shukla et al 2019).…”

Design, Optimization, and Correlation of In Vitro/In Vivo Disintegration of Novel Fast Orally Disintegrating Tablet of High Dose Metformin Hydrochloride Using Moisture Activated Dry Granulation Process and Quality by Design Approach

“…Thanks to its low price, safety, potential cardiovascular protection, and no incidence of weight gain, metformin has been approved for initial therapy of T2DM [ 4 , 5 ]. Recently, clinical studies have indicated that metformin may improve outcomes of several cancers and reduce cancer risk in diabetic patients [ 6 ]. Some other studies showed that metformin might extend the lifespan of people, which led to the ongoing clinical trial “Targeting Aging with Metformin”, aimed at lateness, the process of aging and extend healthy lifespan [ 7 , 8 ].…”