Current Drug Delivery

Mesothelin-Mediated Paclitaxel Phase-Shifted Nanodelivery System for Molecular Ultrasound Imaging and Targeted Therapy Potential in Ovarian Cancer

Background: Ovarian cancer presents a substantial risk to women's health and lives, with early detection and treatment proving challenging. Targeted nanodelivery systems are viewed as a promising approach to enhance the effectiveness of ovarian cancer treatment and ultrasonic imaging outcomes. Objective: A phase-shifted nanodelivery system (NPs) loaded with paclitaxel (PTX) and further conjugated with avidin (Ab) was studied, with the goal of investigating the effects of targeted nanodelivery strategies on the in vitro therapeutic efficacy and ultrasonic imaging of ovarian cancer. This study provides a foundation for future in vivo treatments utilizing this approach. Methods: PTX-NPs were prepared using the single water-in-oil (O/W) emulsion solvent evaporation method, with avidin coupling achieved through biotin-avidin affinity. The encapsulation efficiency and release profile of PTX were analyzed using UV spectrophotometry. The phase-shift properties of the Ab-PTX-NPs delivery system were evaluated, and the targeting efficiency, cytotoxicity against SKOV3 cells, and in vivo biosafety of various nanodelivery systems were assessed. Results: The prepared nanodelivery system showed a stable and uniform structure with a good particle size distribution and exhibited favorable release characteristics under ultrasound exposure. In vitro experiments revealed that the nanodelivery system displayed excellent targeting and cytotoxic effects against SKOV3 cells, indicating the potential of the Ab-PTX-NPs delivery system for targeted ovarian cancer therapy. In vivo safety studies demonstrated the high biosafety of the prepared nanodelivery system. Conclusion: A novel nanodelivery system was developed, and the experimental results obtained provide a solid experimental basis for further research on in vivo ultrasound molecular imaging technology, offering new insights into targeted ultrasound molecular imaging and the treatment of ovarian cancer.

Preparation and In Vitro/Vivo Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery

Aim: Folate-conjugated Pluronic F87-poly(lactic-co-glycolic acid) block copolymer (FA-F87-PLGA) was synthesized to encapsulate anticancer drug Paclitaxel (PTX) for targeted drug delivery. To further improve the curative effect, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was added to form FA-F87-PLGA/TPGS mixed NPs. Methods: FA-F87-PLGA was synthesized by the ring-opening polymerization, and the structure was characterized. PTX-loaded nanoparticles were prepared with the nanoprecipitation method. The physicochemical characteristics were studied to determine the appropriate dose ratio of the FA-F87-PLGA to TPGS. The cytotoxicity against Ovarian Cancer Cells (OVCAR-3) was determined by MTT assay. The Area Under the Curve (AUC) and half-life were measured in the in vivo pharmacokinetic studies. Results: Based on the optimization of particle size and embedding rate of PTX-loaded mixed NPs, the appropriate dosage ratio of FA-F87-PLGA to TPGS was finally determined to be 5:3. According to in vitro release studies, the cumulative release rate of PTX-loaded FA-F87-PLGA/TPGS mixed NPs was 92.04%, which was higher than that of nanoparticles without TPGS. The cytotoxicity studies showed that the IC50 value of PTX-loaded FA-F87-PLGA/TPGS decreased by 75.4 times and 19.7 times after 72 h treatment compared with free PTX injections and PTX-loaded FA-F87- PLGA NPs, respectively. In vivo pharmacokinetic studies indicated that FA-F87-PLGA/TPGS mixed NPs had a longer drug metabolism time and a larger Area Under the Curve (AUC) compared with free PTX injections. Conclusion: FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery systems.

Preparation and In Vitro Evaluation of Thermosensitive Liposomes Targeting Ovarian Cancer

Introduction: Liposomes have been widely used in drug delivery systems because the encapsulation of liposomes changes the biological distribution profile and improves the therapeutic indices of various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells limited their application in safe and efficient chemotherapy. Materials and Methods: In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG) screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000 molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug release behavior of liposomes at different temperatures. The specificity of liposomes to SKOV-3 cells was studied by cell uptake in vitro. Results: The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro. Conclusion: The active targeting liposome showed potential in improving the specificity of thermosensitive liposomes and would be applied in the chemotherapy combined with a thermotherapy.