Etherified pullulan-polyethylenimine based nanoscaffolds improved chemosensitivity of erlotinib on hypoxic cancer cells. (1st November 2021)

• Record Type: Journal Article
• Authors: Bera, Hriday; Abosheasha, Mohammed A.; Ito, Yoshihiro; Ueda, Motoki
• Is Part Of: Carbohydrate polymers. Volume 271(2021)
• Publication Date: 2021-11-01
• Subjects: AMD Amiloride hydrochloride -- AO Acridine orange -- BA Benzoic acid -- CMP Carboxymethyl pullulan -- CPZ Chlorpromazine hydrochloride -- DE Dissolution efficiency -- DEE drug encapsulation efficiency -- DI Initial phase diffusion co-efficient -- DL Late phase diffusion co-efficient -- DMF Dimethylformamide -- DMSO Dimethyl sulfoxide -- DS Degree of substitution -- EB Ethidium bromide -- EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide -- EGFR-TKI Epidermal growth factor receptor tyrosine kinase inhibitors -- HA-MI 6-(2-Methylimidazole)hexylamine -- GPC gel permeation chromatography -- HA-NI 6-(2-Nitroimidazole)hexylamine -- HIF-1α Hypoxia-inducible factor-1α -- ERL Erlotinib hydrochloride -- MDT Mean dissolution time -- MI 2-methylimidazole -- NADPH Nicotinamide adenine dinucleotide phosphate -- NBA Nitrobenzoic acid -- NHS N-hydroxysuccinimide -- NI 2-Nitroimidazole -- PDI Polydispersity index -- PEI Polyethyleneimine -- Pull Pullulan -- TEA triethylamine -- β-CD β-cyclodextrin; Drug delivery -- Pullulan -- Polyethyleneimine -- Nitroaromatic residue -- Hypoxia -- Cervical cancer; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2021.118441
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: The current research endeavor aimed to accomplish hypoxia-responsive polyethyleneimine-conjugated carboxymethyl pullulan-based co -polymer (CMP-HA-NI-PEI-NBA) bearing nitroaromatic subunits to efficiently deliver erlotinib (ERL) to reverse its hypoxia-induced resistance in cancer cells. As compared to a control co-polymer (CMP-HA-MI-PEI-BA) devoid of hypoxia-sensitive moieties, this scaffold demonstrated a hypochromic shift in the UV spectra and rapid dismantling of its self-assembled architecture upon exposure to simulated hypoxic condition. The hypoxia-responsive co -polymer encapsulated ERL with desirable loading capacity (DEE, 63.05 ± 2.59%), causing attenuated drug crystallinity. The drug release rate of the scaffold under reducing condition was faster relative to that of non-reducing environment. Their cellular uptake occurred through an energy-dependent endocytic process, which could exploit its caveolae/lipid raft-mediated internalization pathway. The ERL-loaded scaffolds more efficiently induced apoptosis and suppressed the proliferation of drug-resistant hypoxic HeLa cells than the pristine ERL. Hence, this study presented a promising drug delivery nanoplatform to overcome hypoxia-evoked ERL resistance. Graphical abstract: Unlabelled Image Highlights: Carboxymethyl pullulan/polyethyleneimine basedco-polymer was synthesized. The selective-hypoxic bioreduction of the co-polymer was evidenced. ERL-loaded nanoscaffolds displayed hypoxia-triggered drug release pattern. These exploited caveolae/lipid raft-mediated internalization pathway. These showed an efficient antiproliferative potential on the hypoxic cancer cells.