Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Int J Mol Sci. 2022 Aug 22;23(16):9485. doi: 10.3390/ijms23169485.
This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in -infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.
本研究旨在开发和评估载药固体脂质纳米粒(SLNs)的长期稳定性。SLNs 的设计旨在延长释放曲线,克服生物利用度和溶解度问题,研究毒性,并提高吡喹酮的抗血吸虫病功效。使用溶剂注入共匀化技术来制备 SLNs,其中 Compritol ATO 888 和卵磷脂用作脂质,Pluronic F127(PF127)用作稳定剂,以此来实现这一目标。评估了 PF127 作为稳定剂对 SLNs 的长期稳定性影响。动态光散射(DLS)用于测定粒径、稳定性和多分散性。通过使用透射电子显微镜(TEM)和扫描电子显微镜(SEM)来检查 SLNs 的形态。使用傅里叶变换红外光谱(FTIR)、ElastoSens Bio2、XRPD、DSC 和 TGA 分别评估 SLNs 的化学性质以及机械、热和晶体行为。具有 PF127 的 SLNs 显示出 71.63%的包封效率和 11.46%的载药量。具有 PF127 的 SLNs 的体外药物释放研究表明,在 24 小时内 PZQ 的累积释放率为 48.08%,在 120 天后 SLNs 悬浮液的释放曲线相似。DLS、ELS 和光学特性以及稳定性分析数据表明,添加 PF127 作为表面活性剂为 SLNs 提供了长期稳定性。体外细胞活力和体内毒性评价表明,用 PF127 稳定的 SLNs 是安全的。总之,寄生虫学数据表明,在感染的小鼠中,单次(250mg/kg)口服剂量的 CLPF-SLNs 在感染后两周和四周均可显著提高 PZQ 的抗血吸虫病功效。因此,所制备的 CLPF-SLNs 在 PZQ 的递送上表现出显著的效率,因此是一种有前途的抗血吸虫病治疗策略。