Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release.

Autor: Cano-Cortes MV; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.; Department of Medicinal & Organic Chemistry, Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital, Av. del Conocimiento, s/n, 18016 Granada, Spain., Laz-Ruiz JA; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.; Department of Medicinal & Organic Chemistry, Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital, Av. del Conocimiento, s/n, 18016 Granada, Spain., Diaz-Mochon JJ; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.; Department of Medicinal & Organic Chemistry, Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital, Av. del Conocimiento, s/n, 18016 Granada, Spain., Sanchez-Martin RM; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.; Department of Medicinal & Organic Chemistry, Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital, Av. del Conocimiento, s/n, 18016 Granada, Spain.
Jazyk: angličtina
Zdroj: Polymers [Polymers (Basel)] 2020 Jun 01; Vol. 12 (6). Date of Electronic Publication: 2020 Jun 01.
DOI: 10.3390/polym12061265
Abstrakt: Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release.
Databáze: MEDLINE
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