Abstract
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10−7 M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs.Graphical Graphical of CA-PEI-pArg polymeric micelles as a pH-responsive drug delivery system.
Highlights
Chemotherapy is one of the most commonly used approaches to cancer treatment
These results demonstrated the presence of an amide linkage in the Cholic acid (CA)-PEI-pArg copolymer
Comparison of the 1H NMR spectra of the triblock copolymer (Fig. 1ii (d)) with those of the other components (Fig. 1ii (a–c)) showed that distinct chemical shifts attributable to different components were present in the spectrum of the CA-PEI-pArg copolymer
Summary
Chemotherapy is one of the most commonly used approaches to cancer treatment. Conventional chemotherapeutics cause numerous unfavorable side effects owing to poor water solubility, a lack of selectivity towards cancer cells, and multi-drug resistance [1]. Doxorubicin (DOX) is used to treat breast cancer, ovarian cancer, lymphoma, multiple myeloma, and sarcoma [2]. Clinical use of DOX is limited by its side effects, which include drug resistance and cardiotoxicity. The P-glycoprotein efflux pump contributes to multidrug resistance in cancer cells, reducing the efficacy of chemotherapeutic agents [3]. Higher dose of DOX is needed to achieve the similar chemotherapeutic
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