Liposomal Nanodrug Based on Norcantharidin Derivative for Increased in Vivo Activity.

To address the limitations of norcantharidin (NCTD) in clinical applications, including restricted tumor accumulation and intense irritation, we have developed a new derivative of NCTD with (S)-1-benzyl-3-pyrrolidinol, which can be actively loaded into liposomes to achieve drug encapsulation and sustained release properties by using pH gradient loading technique. Cytotoxicity tests against cancer cell lines (Hepa 1-6 and 4 T1 cells) have demonstrated that this derivative exhibits comparable activity to NCTD in vitro. The NCTD derivative can be efficiently loaded into liposomes with high encapsulation efficiency (98.7%) and high drug loading (32.86%). Tolerability and antitumor efficacy studies showed that the liposomal NCTD derivative was well tolerated at intravenous injection doses of 3 folds higher than the parent drug solution, while significantly improved anticancer activity in vivo was achieved. This liposomal nanodrug could become a potent and safe NCTD formulation alternative for cancer therapy.

Characterization techniques: The stepping stone to liposome lyophilized product development.

The primary drying is the longest step of the freeze-drying process and becomes one of the focuses for lyophilization cycle development inevitably, which is often approaching through a "trial and error" course and requires a labor-intensive and time-consuming endeavor. Nevertheless, drawing support from characterization techniques to understand the physic-chemical properties changing of the sample during lyophilization and their correlation with process conditions comprehensively, the freeze-drying development and optimization will get more from less. To get the optimal lyophilization cycle in the least time, the instrumental methods assisting primary drying design are summarized. The techniques used for estimating the collapse temperature of products are reviewed at first, aiming to provide a reference on the primary drying temperature setting to guarantee product quality. The instrumental methods for primary drying end prediction are also discussed to get optimal freeze-drying protocol with higher productivity. This review highlights the practicality of the above techniques through expounding basic principles, typical measurement conditions, merits and drawbacks, interpretation of results and practical applications, etc. At last, the techniques used for residual moisture detection of lyophilized products and size determination after liposome rehydration are briefly introduced.

Irinotecan and berberine co-delivery liposomes showed improved efficacy and reduced intestinal toxicity compared with Onivyde for pancreatic cancer.

Onivyde is the first irinotecan (IRI) nanoliposome that could improve pharmacokinetics and tumor biodistribution of irinotecan. Although FDA approves Onivyde for the treatment of pancreatic cancer patients who are not effective for GEM, the gastrointestinal toxicity caused by Onivyde is still a problem to be solved in clinical application. Berberine (BER), an isoquinolone alkaloid extracted from several different plants, has been reported to exhibit beneficial effect in alleviating intestinal mucositis and generating synergistic anticancer effect in combination with cytotoxic drugs. However, its therapeutic effect is affected by the different pharmacokinetic behavior of two drugs. Therefore, we utilized triethylamine-sucrose octasulfate gradient to construct nanoliposomes for co-delivery of irinotecan and berberine, termed as lipBI. This co-delivery nanoliposomes remained the synergistic ratio in the body and improved tumor distribution of IRI and BER. The lipBI significantly inhibited tumor growth in the BXPC-3 pancreatic cancer model compared with Onivyde (p < 0.05) and reduced the gastrointestinal toxicity in mice caused by IRI. Overall, IRI/BER co-loaded liposomes possessed great potential in the treatment of pancreatic cancer.