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Sequential Release of Paclitaxel and Imatinib from Core-Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer.

ABSTRACT: To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core-shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core-shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core-shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.

SUBMITTER: Liu Z

PROVIDER: S-EPMC8395827 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBerberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability.ObjectiveIn this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR.MethodsThree-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs.ResultsBased on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC50 = 56 μM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC50 > 150 μM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations.ConclusionsA new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.

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Sequential Release of Paclitaxel and Imatinib from Core-Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer.

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