Abstract
Pingyangmycin (PYM) has been applied clinically for many years to treat vascular malformations (VM) in China. The major limitation of PYM injections is quick diffusion from the injection site, which increases side effects, especially the possibility of pulmonary injury. In this paper, chitosan/glycerophosphate disodium (CS/GP) thermogels containing liposomes for sustained and localized PYM delivery were prepared and optimized by a three-level three-factorial Box–Behnken experimental design to evaluate the effects of different variables (the PYM concentration, CS amount and GP content), on the selected responses (cumulative percentage PYM released in 1 day, 9 days and the rate constant k). The results revealed that the optimized PYM liposomal thermogels had a controlled PYM release for 14 days in vitro, which confirmed the validity of optimization. In vitro morphological observation, cell cycle and apoptosis analysis showed an effective anti-proliferation action of PYM liposomal thermogels on human vascular endothelial cells (EA.hy926). In vivo pharmacokinetics research in rabbits displayed that compared with PYM liposomes and PYM thermogels, PYM liposomal thermogels had a better controlled delivery of PYM. Histological examination of rabbit ear veins showed that after local application with PYM lipsomal thermogels for 21 days, obvious vein thrombosis and inflammatory reaction could be observed. The above results indicated that PYM-loaded lipsomal CS/GP thermogels might have a good prospect for the treatment of VM.
Highlights
Hydrogel is composed of network polymers dispersed in a lot of water, which has been widely concerned in the field of biomedical research for its good formulation stability and bio-compatibility (Dou et al, 2014; Zheng et al, 2015)
An in vitro and in vivo evaluation of PYM-loaded liposomal chitosan/glycerophosphate disodium (CS/glycerol phosphate disodium (GP)) in situ thermogels was conducted for the treatment of vascular malformations (VM)
The optimal formulation was composed of PYM 4.68 mg/mL, CS 2.05% (w/v), and GP 11.57% (w/v), producing in situ gels with 17.24% and 80.77% PYM released in 1 day and 9 days, respectively, and rate constant of 0.0808
Summary
Hydrogel is composed of network polymers dispersed in a lot of water, which has been widely concerned in the field of biomedical research for its good formulation stability and bio-compatibility (Dou et al, 2014; Zheng et al, 2015). The preparation of in situ gel through a simple solgel method with no chemical reaction is a focus in the research for hydrogel, which allows the hydrogel more suitable for the application in controlled drug delivery and biomedical engineering (Wu et al, 2016; Yu et al, 2017). Chitosan (CS) has been widely used in the field of pharmaceutics, medicine and tissue-engineering, because of its bio-degradability, low toxicity and good bio-compatibility. Paclitaxel-loaded CS-based thermogels were studied by intra-tumor injection into tumor-bearing mice, whose findings displayed that compared with Taxol injections, the paclitaxel-loaded thermogels could more effectively inhibit tumor growth and reduce systemic toxicity (Mahajan et al, 2016)
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