The purpose of this study was to develop a safe and effective drug delivery system for local chemotherapy. A novel injectable in-situ-forming gel system was prepared using small molecule materials, including phospholipids, medium chain triglycerides (MCTs), and ethanol. Thus, this new sustained release system was named PME (first letter of phospholipids, MCT, and ethanol). PME has a well-defined molecule structure, a high degree of safety, and better biocompatible characteristics. It was in sol state with low viscosity in vitro and turned into a solid or semisolid gel in situ after injection. When loaded with doxorubicin (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro, PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer cells for over 5 days. Moreover, the initial burst effect can hardly be observed from PME system, which was different from many other in-situ-forming gels. The in vivo biodistribution study showed the high Dox concentration in tumors compared with other major organs after PME-D intratumoral administration. The strong signal in tumors was retained for more than 14 days after one single injection. The high concentration of Dox in tumor and long-term retention may explain the superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming gel system is a promising drug delivery system for local chemotherapy.

Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor. However, its potential side effects are prominent and clinical use is restricted. We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared THP-OA-AN was characterized and animal experiments were conducted to assess its tumor suppression effect, distribution, and toxicity. Comparison between THP and THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA-AN is significantly reduced regarding bone marrow suppression, cardiotoxicity, renal toxicity, and gastrointestinal toxicity. This study developed a safe and effective formulation of THP, which has greater potential for clinic use in the tumor therapy.

No abstract

No abstract

No abstract

No abstract

No abstract

No abstract