Topotecan hydrochloride liposomes incorporated into thermosensitive hydrogel for sustained and efficientin situtherapy of H22 tumor in Kunming mice

Abstract

Topotecan hydrochloride (TPT) has potential for the treatment of ovarian cancer, but the activity of TPT tends to decrease due to the ring-opening at physiological pH. In this study, we proposed to incorporate TPT liposomes into injectable thermosensitive in situ hydrogel, consisting of chitosan (CS) and β-glycerophosphate (β-GP), for sustained release and preservation of active lactone form of TPT. The rheology studies were carried out to investigate the sol-gel temperature, flow behavior and viscosity of these CS/β-GP systems. The optimized formulation exhibited sol-gel transition at 40.2 ± 0.4 °C, with pseudoplastic flow behavior. The drug release rate of TPT liposomes loaded CS/β-GP hydrogel in phosphate buffer saline (pH = 7.4) was found to be slowed down, and the lactone fraction of TPT in the hydrogel matrix was maintaining 40% after 50 h. In addition, the antitumor efficacy in Kunming mice bearing Hepatoma-22 tumor, after intratumoral injection of TPT liposomes loaded CS/β-GP hydrogel, was higher than that of TPT in saline and TPT in CS/β-GP hydrogel. Those results demonstrated that TPT liposomes loaded CS/β-GP hydrogel could become a potential formulation for improving the antitumor efficacy of TPT and suggested an important technology platform for intratumoral administration of derivative of camptothecin-family drugs.

Liposomes‐in‐Chitosan Hydrogels: Challenges and Opportunities for Biomedical Applications

“…Although the mechanism is not yet clear, it is believed that there is a production of immunoglobulin M (IgM) after the first liposome injection. As a consequence, IgM is able to bind selectively to another PEGylated liposome which leads to rapid elimination by promoting hepatic uptake (129,130). In addition to obtaining hydrogel materials that are able to respond to temperature stimuli and trigger the release of a chemotherapeutic drug, other important therapeutic strategies have been also developed to favor controlled drug release.…”

“…B) In vitro cumulative release of TPT, free or both free and liposomal, released from the TPT liposomes-loaded CS/-GP hydrogel in PBS (pH 7.4, 0.05 M) at 37 ± 0.5 ºC (mean ± SD, n = 6). Adapted with permission from reference(130).Copyright 2014 Taylor & Francis. In vivo experiments with Kunming mice bearing H22-tumor were carried out by intratumoral injection employing CS/GP-TPTC-liposomes with several control experiments (i.e.…”

Research progress in the application of in situ hydrogel system in tumor treatment

“…The researchers in the related fields have tried to develop in situ hydrogel system achieving two main goals of drug administration: the first one is to specifically and safely deliver and target the drug to its site of action through local drug delivery (intratumor/paratumor) to maximize its therapeutic efficacy while minimizing its toxicity, based on enhanced antitumor activity with increasing concentration of anti-tumor drugs at the target site (tumor); the second one is to extend the duration of the tumor's exposure to the drug and maintain its release from the formulated drug carrier to help maintain its therapeutic effect after administration. The in situ hydrogel forms a drug depot at the injection site, which may reduce the total number of injections throughout the drug treatment process (Bendas et al, 2013;Moghassemi & Hadjizadeh, 2014;Shaker et al, 2015;Xing et al, 2015Xing et al, , 2019Omidi et al, 2020). In order to summarize and improve study the application of in situ hydrogel system in tumor treatment, this paper focuses on the recent research progress in related areas.…”

Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway

“… 12 Liposomal TP has improved the anticancerous efficacy of TP in Kunming mice with Hepatoma-22 tumor as well as in patients with neuroblastoma. 13 , 14 …”