BackgroundSN38 (7-ethyl-10-hydroxycamptothecin) is a camptothecin derivative acts against various tumors. However, SN38 is hydrolyzed in the physiological environment (pH 7.4), and this instability interferes with its potential therapeutic effect. Our objective was to investigate SN38-loaded liposomes to overcome the poor solubility of SN38 and its biodistribution, which further diminish its toxicity.Materials and methodsThe sub-100 nm targeted liposomes was employed to deliver SN-38 and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.ResultsThe SN38-loaded targeted liposomes consisted of small (100.49 nm) spherical nanoparticles with negative charge (−37.93 mV) and high entrapment efficiency (92.47%). The release behavior of the SN38-loaded targeted liposomes was fitted with Higuchi kinetics (R2=0.9860). Free SN38 presented initial burst release. The IC50 for the SN38-loaded targeted liposomes (0.11 μM) was significantly lower than for the SN38 solution (0.37 μM) in the MCF7 cell line (P<0.01). Confocal laser scanning microscopy also confirmed highly efficient accumulation in the MCF7 cells. Pharmacokinetics demonstrated that the SN38-loaded targeted liposomes had a slightly increased half-life and mean residence time and decreased area under the concentration–time curve and maximum concentration. The results suggested that retention was achieved while the exposure of SN38 was significantly decreased. A noninvasive in vivo imaging system also showed that the targeted liposomes selectively targeted MCF7 tumors. In vivo toxicity data demonstrated that the decrease in platelets was significantly improved by SN38-loaded targeted liposomes, and diarrhea was not observed in BALB/c mice.ConclusionIn summary, SN38-loaded targeted liposomes could be a good candidate for application in human breast cancer.
Camptothecin (CPT) is plant alkaloid exhibiting in a wide range of solid tumours. However, CPT was instability at physiological pH conditions, the lactone moieties easily hydrolysed makes systemic toxicity risky. Moreover, the water insolubility of CPT was obstructed in clinical development. The aim of the study was to utilise nontoxic and biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) incorporated lipid as a hybrid nanoparticle (lipid-PLGA NPs) for delivery of CPT. Lipid-PLGA NPs were produced by a nano-precipitation technique. The optimal formulation was presented that particles of which were 43 nm in diameter, with a polydispersity index of 0.3 which indicated a smaller and well-distributed pattern. Moreover, a high capacity of ∼95% entrapment efficiency was achieved. An in vitro release study showed that non-formulated CPT with a lag time of ∼0 h, demonstrated an obvious burst effect; in contrast, sustained released and a lag time delay were clearly observed in lipid-PLGA NPs. The cytotoxicity study confirmed that human ovarian cancer cells (ES-2) were inhibited by lipid-PLGA NPs. CPT was successful entrapped in lipid-PLGA NPs which achieved smaller size and well distribution. Lipid-PLGA NPs resolve the water insolubility and produced a sustained, slow-release pattern of CPT and controlled the cytotoxicity toward ES-2.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.