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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Intratumoral injection of gels containing losartan microspheres and (PLG-g-mPEG)-cisplatin nanoparticles improves drug penetration, retention and anti-tumor activity.
Cancer Letters 2019 Februrary 2
Intratumoral injection of chemotherapy agents may be employed in the treatment of cancers. However, its anti-tumor efficacy is significantly impeded by collagen fibers in the tumor which decrease drug penetration into the tumor tissues. To improve the penetration, collagen inhibiting drug exposure is required. In this study, microspheres were fabricated by the modified double emulsion-solvent evaporation method as the drug delivery system of losartan potassium (LP MSs), with 5% gelatin as the inner phase. The collagen inhibiting experiment analyzed by Sirius Red stains demonstrated that LP MSs may effectively inhibit collagen I synthesis in B16 tumors. In addition, 15% F127 was used as the solvent to fix the formulations at the injection site, with poly (α-l-glutamate) grafted polyethylene glycol mono methyl ether (PLG-g-mPEG)-cisplatin loaded nanoparticles (CDDP NPs) as the model drug. The in vivo live imaging system showed that formulations dissolved in 15% F127 had 54.91% CDDP NPs retained in tumors at the end of 10 days, in comparison with 19.72% for those solved in water, suggesting strong intratumoral retention property of the in situ gel. In addition, confocal laser scanning microscope (CLSM) and Energy-Dispersive Analysis of X-ray spectroscopy combined with scanning electron microscope (SEM-EDAX) tests showed that LP MSs can effectively enhance the distribution and penetration of CDDP NPs within tumors. Furthermore, tumors i.t. treated with LP MSs/CDDP NPs gel could be significantly halted, or even reduced to 200 mm3 , comparing with a volume of about 12000 mm3 incontrol group at the end of the anti-tumor effect experiment. These results provided important guiding principles for prolonged and localized drug delivery system of intratumoral collagen inhibitor. The improvements of intratumoral penetration method made in this study provided practical significance for the treatment of cancer, especially for mass tumors.
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