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.

Aim: Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Methods: Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). Results: The Bre-NLCs were spherical with a mean particle size of ~170 nm, a zeta potential of ~20 mV and a high entrapment efficiency of ~89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC 0-t and a 12 times increase in T 1/2 as compared to the commercially available breviscapine solution. Conclusion:The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine.

As a natural somatostatin analog, octreotide acetate (OCT) has been extensively used in cancer treatment and growth hormone related diseases. The clinical application of OCT, however, is greatly limited by its short half-life, rapid elimination and clearance in vivo. In the current study, a high content phospholipid-based phase separation gel platform (PPSG) was presented, which could be injected in the soluble state and underwent rapid phase-separation into a gel-like implant after a single subcutaneous injection. OCT was dispersed homogeneously in the PPSG pre-gel solution to afford OCT-loaded PPSG (OCT-PPSG) after a single subcutaneous injection, which displayed controlled and sustained release profiles for up to 30days in rats, rabbits and Beagle dogs. OCT-PPSG showed a less significant burst phase followed by a steady plasma concentration of OCT compared with Sandostatin(®) (LAR) in Beagle dogs. Moreover, OCT-PPSG was demonstrated to show remarkable antitumor efficacy in both a primary rat model and a xenograft mouse model of hepatocellular carcinoma (HCC). PPSG thus represented a promising and viable in situ forming gel platform material for the long-term sustained release of peptides and protein drugs.