Preparation and Characterization of Celecoxib-Conjugated Polyethylenimine as a Potential Nanocarrier for Gene Delivery
Journal Title: Trends in Pharmaceutical Sciences - Year 2018, Vol 4, Issue 1
Abstract
The objective of the present investigation was to conjugate celecoxib as a cyclooxygenase-2 (COX-2) inhibitor onto polyethylenimine (PEI) in order to prepare nanoparticles for tissue targeting. Since celecoxib binds to COX-2 and this enzyme is over expressed in several pathological conditions including cancer, the final goal of the study was to direct the nanoparticles into specific tissues. Celecoxib was conjugated on PEI structure at two substitution degrees of 5 and 10 % and the new conjugates were characterized in terms of size, zeta potential, buffering capacity, plasmid DNA binding affinity and protection against enzymatic degradation as well as cytotoxicity. The results demonstrated the ability of the PEI conjugates in the formation of nanoparticles with the size of around 200 nm with buffering capacity comparable with unmodified PEI. The celecoxib conjugated PEI derivatives demonstrated high binding affinity to pDNA and protection effect against degradation by DNase I. The conjugation of celecoxib onto PEI structure slightly reduced the toxic effects of unmodified PEI especially at the conjugation degree of 10%. However, this result showed that the significant decrease of PEI cytotoxic effects could not be achieved by the shielding of surface amines even at the conjugation degree of 10%. Therefore, it is suggested to investigate the effects of higher degrees of amine substitution to produce less toxic PEI -based nanocarriers.
Authors and Affiliations
Hossein Sadeghpour, Kobra Roshan Nasrabad, Marjan Alipour Haghighi, Ali Dehshahri
Keywords
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