Development of rosuvastatin flexible lipid-based nanoparticles: promising nanocarriers for improving intestinal cells cytotoxicity

Abstract

Background: Rosuvastatin (RSV) is a poorly water-soluble drug that has an absolute oral bioavailability of only 20%. The aim of this work was to prepare a positively charged chitosan coated flexible lipid-based vesicles (chitosomes) and compare their characteristics to the corresponding negatively charged flexible liposomal nanoparticles (NPs) in order to develop new RSV nanocarrier systems. Methods: Three formulation factors affecting the development of chitosomes nano-formulation were optimized for their effects on the particles size, entrapment efficiency (EE) and zeta potential. The optimized flexible chitosomes and their corresponding liposomal NPs were characterized for morphology, in vitro release, flexibility and intestinal cell viability. The half maximum inhibitory concentrations (IC50) for both formulations were calculated.Results: The drug to lipid molar ratio, edge activator percent and the chitosan concentration were significantly affecting the characteristics of NPs. The optimized chitosomes nano-formulation exhibited larger size, higher EE and greater zeta potential value when compared to the corresponding liposomal NPs. Both formulations showed a spherical shape nanostructure with a marked outer shell for the chitosomes nano-formulation. Chitosomes illustrated an extended drug release profile when compared with the corresponding liposomal NPs and the prepared drug suspension. Flexibility of both vesicles was confirmed with superiority of liposomal NPs over chitosomes. RSV loaded chitosomes nano-formulation exhibited lower IC50 values and higher therapeutic window while liposomal NPs were compatible with the intestinal cells. Conclusions: RSV loaded chitosomes nano-formulation could be considered as a promising nanocarrier system with a marked cytotoxic activity while, RSV loaded liposomal NPs are suitable nanocarrier to improve RSV activity in treatment of cardiovascular disorders.

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells

“…Thin-film hydration technique was used to develop a positively charged and neutral liposomal formulations loaded with 6-mercaptopurine [7,9,21,22]. This technique was selected as it is the most common and simple for development of all kinds of lipid-based nanoparticles, but the process must be optimized to achieve high encapsulation and homogenous size distribution.…”

“…A positively charged drug-loaded liposomes (F1), uncharged drug-loaded liposomes (F2), nonmedicated positively charged liposomes (F3), and non-medicated uncharged liposomes (F4) were developed. Selection of the drug to lipid ratio, percentage of tween 80 and the percentage of charge inducing agent was based on our previously published work for optimization of the formulation components used to develop flexible lipid based liposomal [7,23]. A drug to phospholipid molar ratio of 1: 1.7 was used.…”

“…The amount of 6-MP entrapped in the liposomal formulations was calculated indirectly as previously mentioned [7]. The prepared 6-MP loaded liposomes were centrifuged using 3 K30 Sigma Laboratory centrifuge (Ostrode, Germany) for 1 h at 20,000 rpm at 4 • C. The supernatant, containing the un-entrapped drug, was taken, filtered using an Acrodisc ® 0.2 syringe filter and the drug concentration in the filtered sample was determined spectrophotometrically at 332 nm.…”

“…Lipid-based NPs may be classified into phospholipid and non-phospholipid vesicles. The former includes liposomes, transfersomes, ethosomes, and trans-ethosomes [7][8][9] while, the latter comprises solid lipid NPs [10], nanostructured lipid carriers [11], polymeric micelles [12,13], niosomes [14], nano-emulsions [15], and dendrimers [16]. The liposome has a structure comparable to the cell membrane, which has two phospholipid layers and is spherical in form.…”

Development and evaluation of luteolin loaded pegylated bilosome: optimization, in vitro characterization, and cytotoxicity study

“…The lipid-based nanocarrier systems have been used to enhance the solubility as well as therapeutic activity. These systems include eplerenone nanostructured lipid carriers (NLCs) (Abd-Elhakeem et al., 2021 ), rosuvastatin liposomes (Ahmed, 2020 ), lovastatin hybrid liposome (Romana et al., 2020 ), glycyrrhizic acid and cisplatin nanoliposomes (Hatami et al., 2020 ), Fumaria officinalis niosomes (Raafat & El-Zahaby, 2020 ), apigenin, piceatannol bilosomes (Alhakamy et al., 2021 ; Zafar et al., 2021 ), and olmesartan medoxomil pegylated bilosomes (PG-BLs) (Albash et al., 2019 ). Among them, PG-BLs are the new approach for the improvement of the therapeutic efficacy of the poorly soluble drugs.…”