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.

Electrosprayed Core (Cellulose Acetate)–Shell (Polyvinylpyrrolidone) Nanoparticles for Smart Acetaminophen Delivery

“…One of the most difficult challenges in pharmaceutics is the dissolution and effective delivery of poorly water-soluble APIs [ 73 , 74 ]. The existence state of these poorly water-soluble APIs in the raw powders is mainly crystalline, which makes them difficult to disperse in the body fluids.…”

Review on electrospray nanoparticles for drug delivery: Exploring applications

“…182,183 Furthermore, numerous studies have explored the use of electrosprayed formulations to improve the delivery of drugs such as paclitaxel, doxorubicin, methotrexate, gemcitabine, camptothecin, docetaxel, cisplatin, and etoposide. 153,155,[184][185][186][187][188][189] Other approaches, such as PLGA porous beads as microscaffolds 190 and oxygen release systems, 107 have also been investigated for cardiomyoplasty. Injectable hydrogels combining drug-loaded alginate microspheres with PLGA-PEG-PLGA hydrogels have also been developed.…”

“…Khare et al 182 created electrosprayed lipid nanoparticles for siRNA delivery, while Swetledge et al 183 formulated polymeric nanoparticles for ocular drug delivery, resulting in improved cellular uptake, gene silencing, bioavailability, and sustained release 182,183 . Furthermore, numerous studies have explored the use of electrosprayed formulations to improve the delivery of drugs such as paclitaxel, doxorubicin, methotrexate, gemcitabine, camptothecin, docetaxel, cisplatin, and etoposide 153,155,184–189 . Other approaches, such as PLGA porous beads as microscaffolds 190 and oxygen release systems, 107 have also been investigated for cardiomyoplasty.…”

Microparticles in the Development and Improvement of Pharmaceutical Formulations: An Analysis of In Vitro and In Vivo Studies

“…The association of two or more drugs to improve the treatment of cancer patients can be a challenge, as interactions between drugs may occur. To associate paclitaxel (PTX) and imatinib (IMN), Liu et al [ 25 ] prepared polymeric microcapsules with external enclosure of PTX-loading hyaluronate and IMN-loading PLGA nucleus, to be vaginally administered for cervical cancer treatment. The in vitro release study showed a two-step release pattern: in the former step approximately 80% of PTX contained in the outer layer was quickly released, while in the latter, of the sustained type, approximately 90% of IMN was released within 7 days.…”