Hydrophobically Modified Keratin Vesicles for GSH-Responsive Intracellular Drug Release

Abstract

Redox-responsive polymersomes were prepared by self-assembly of a hydrophobically modified keratin and employing a water addition/solvent evaporation method. Polyethylene glycol-40 stearate (PEG40ST) was chosen as hydrophobic block to be coupled to keratin via radical grafting. The amphiphilic polymer exhibited low critical aggregation concentration (CAC; 10 μg/mL), indicating a good thermodynamic stability. The polymeric vesicles loaded both hydrophilic methotrexate and hydrophobic curcumin with high entrapment efficiencies, and showed a GSH-dependent drug release rate. Confocal studies on HeLa cells revealed that the obtained polymersomes were efficiently internalized. Biocompatibility properties of the proposed delivery vehicle were assessed in HET-CAM test and Balb-3T3 mouse fibroblasts. Polymersomes loaded with either methotrexate or curcumin inhibited HeLa and CHO-K1 cancer cells proliferation. Overall, the proposed keratin polymersomes could be efficient nanocarriers for chemotherapeutic agents.

Polyphenols delivery by polymeric materials: challenges in cancer treatment

“…The main advantages of such materials are the high biocompatibility and improved CUR efficiency on cervical (Sahu et al, 2008b;Curcio et al, 2015a) and lung (Curcio et al, 2015b) cancer cells in vitro and ovarian cancer with negligible immunogenicity in mice (Podaralla et al, 2012). Amphiphilic behavior was conferred to CT by conjugation with STA, allowing the obtainment of CUR carrier for the treatment of colon cancer both in vitro (primary cancer cells) and in vivo (orthotopic mice) with improved efficiency (Wang et al, 2012b).…”

Drug‐Conjugation Induced Self‐Assembly of Feather Keratin‐Based Prodrug for Tumor Intracellular Reduction Triggered Drug Delivery

“…Beside a higher cysteine contents (7–20% of all amino acids) than other natural proteins, there are also plentiful active groups such as carboxyl and amino groups . By now, several keratin‐based DDSs have been reported for the controlled release of antitumor drugs, in which the drugs were loaded via electrostatic interaction or hydrogen bond, with disulfide crosslinking of the thiol groups in keratin, glutaraldehyde, or not . Because keratin contains more carboxyl groups than amino groups with a low isoelectric point (pI) of about 4.5, the keratin‐based DDSs could swell more obviously in the basic media than in the acidic media, resulting distinct drug leakage during blood circulation.…”

“…[8] By now, several keratinbased DDSs have been reported for the controlled release of antitumor drugs, in which the drugs were loaded via electrostatic interaction or hydrogen bond, [9][10][11][12][13][14][15] with disulfide crosslinking of the thiol groups in keratin, [9][10][11] glutaraldehyde, [12] or not. [13][14][15] Because keratin contains more carboxyl groups than amino groups with a low isoelectric point (pI) of about 4.5, [13] the keratinbased DDSs could swell more obviously in the basic media than in the acidic media, resulting distinct drug leakage during blood circulation. Different from the reported works with modified keratin from its thiol groups, [9,10,13] the carboxyl groups in the feather keratin was PEGylated to increase its pI to >10.…”

“…[13][14][15] Because keratin contains more carboxyl groups than amino groups with a low isoelectric point (pI) of about 4.5, [13] the keratinbased DDSs could swell more obviously in the basic media than in the acidic media, resulting distinct drug leakage during blood circulation. Different from the reported works with modified keratin from its thiol groups, [9,10,13] the carboxyl groups in the feather keratin was PEGylated to increase its pI to >10. As a result, the premature drug leakage from the PEGylated keratin (PK) core-crosslinked micelles was reduced to 14% in the simulated normal physiological medium in 3 d. [11] Recently, the drug-conjugation induced self-assembly technique has been developed for the formulation of nanomedicines.…”

HPLC–MS/MS method for quantification of paclitaxel from keratin containing samples

“…Keratin is a protein extracted from hair and a widely used biomaterial that represents potential as a novel paclitaxel excipient. 19–21 Keratin is highly biocompatible, has intrinsic scaffolding capability, supports release of several drugs and factors, and promotes anti-inflammation in vivo . 19, 22–26 Both keratose and kerateine are accumulations of protein/protein fragments and isoforms of various sizes.…”