title: Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells.
abstract: Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.
authors: Novel Drug Delivery Systems Lab, Tehran University of Medical Sciences, Tehran, Iran.
authors: Fatemeh
authors: F
authors: Talaei
authors: Ebrahim
authors: E
authors: Azizi
authors: Rassoul
authors: R
authors: Dinarvand
authors: Fatemeh
authors: F
authors: Atyabi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects*; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D013864:Thioglycolates / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D020319:Oligodeoxyribonucleotides, Antisense; D013864:Thioglycolates; D004317:Doxorubicin; D048271:Chitosan; D066246:ErbB Receptors