Controlled Release of Doxorubicin from Doxorubicin/γ‐Polyglutamic Acid Ionic Complex

Abstract

Formation of drug/polymer complexes through ionic interactions has proven to be very effective for the controlled release of drugs. The stability of such drug/polymer ionic complexes can be greatly influenced by solution pH and ionic strength. The aim of the current work was to evaluate the potential ofγ-polyglutamic acid (γ-PGA) as a carrier for the anticancer drug, Doxorubicin (DOX). We investigated the formation of ionic complexes betweenγ-PGA and DOX using scanning electron microscopy, spectroscopy, thermal analysis, and X-ray diffraction. Our studies demonstrate that DOX specifically interacts withγ-PGA forming random colloidal aggregates and results in almost 100% complexation efficiency. In vitro drug release studies illustrated that these complexes were relatively stable at neutral pH but dissociates slowly under acidic pH environments, facilitating a pH-triggered release of DOX from the complex. Hydrolytic degradation ofγ-PGA and DOX/γ-PGA complex was also evaluated in physiological buffer. In conclusion, these studies clearly showed the feasibility ofγ-PGA to associate cationic drug such as DOX and that is may serve as a new drug carrier for the controlled release of DOX in malignant tissues.

The endocytic pathway and therapeutic efficiency of doxorubicin conjugated cholesterol-derived polymers

“…17 One of the many approaches to overcome these limitations and enhance the efficacy of DOX is by utilizing polymers as drug carriers. Various polyanions such as polyglutamate; 18 polyaspartate, 19 poly(acrylic acid), 20,21 γ-polyglutamic acid, 22 block ionomers of aspartate, benzyl glutamate 23 and benzyl aspartate 24 with poly-(ethylene oxide) have demonstrated encouraging results in terms of binding and delivering DOX into targeted cells and tissues. Consequently, anionic poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA) copolymer series -comprised of enriched electrostatic binding abilities and pHresponsive/membrane disruptive properties -were investigated as potential DOX carriers.…”

Easy on-demand self-assembly of lateral nanodimensional hybrid graphene oxide flakes for near-infrared-induced chemothermal therapy

“…27 DOX possesses a characteristic λ max at 480 nm. 28 This peak was also observed in the nGO@DOX dispersion, thereby supporting that DOX incorporation with nGO flakes did not change the optical properties of the nGO (no significant peak changes at 232 and 302 nm). Fourier transform infrared measurements were performed, as presented in Supplementary Figure S2C.…”

Transmission of External Environmental pH Information to the Inside of Liposomes <i>via</i> Pore-Forming Proteins Embedded within the Liposomal Membrane

“…Previously, it was reported that the increase of γ-PGA ratio improved the formation efficiency of γ-PGA/Dox ionic complex and solubilized them to water by concealing hydrophobic part of Dox into deeper side of the complex. 19) Therefore, increasing the size of PGA : Dox complexes along to PGA ratio shown in Table 2 might be resulted from that each Dox molecules interacted with more PGA chain along to PGA ratio. When PGA ratio is too low (like PGA : Dox=5 : 1), hydrophobic part of Dox might be exposed to the surface of complex, hereby the complexes were aggregated by hydrophobic interaction.…”

“…19) PGA/Dox was prepared by mixing 1 mg/mL (200 µg) PGA and 0.1 mg/mL (20 µg) Dox in liposomal buffer for 30 min at room temperature. SUVs were prepared as follows.…”