Controlled release of doxorubicin from pH-responsive microgels

Abstract

Stimuli-responsive hydrogels have enormous potential in drug delivery applications. They can be used for site-specific drug delivery due to environmental variables in the body such as pH and temperature. In this study, we have developed pH-responsive microgels for the delivery of doxorubicin (DOX) in order to optimize its anti-tumor activity while minimizing its systemic toxicity. We used a copolymer of oligo(polyethylene glycol) fumarate (OPF) and sodium methacrylate (SMA) to fabricate the pH-responsive microgels. We demonstrated that the microgels were negatively charged, and the amounts of charge on the microgels were correlated with the SMA concentration in their formulation. The resulting microgels exhibited sensitivity to the pH and ionic strength of the surrounding environment. We demonstrated that DOX was efficiently loaded into the microgels and released in a controlled fashion via an ion-exchange mechanism. Our data revealed that the DOX release was influenced by the pH and ionic strength of the solution. Moreover, we designed a phenomenological mathematical model, based on a stretched exponential function, to quantitatively analyze the cumulative release of DOX. We found a linear correlation between the maximum release of DOX calculated from the model and the SMA concentration in the microgel formulation. The anti-tumor activity of the released DOX was assessed using a human chordoma cell line. Our data revealed that OPF–SMA microgels prolonged the cell killing effect of DOX.

pH-responsive drug release from functionalized electrospun poly(caprolactone) scaffolds under simulatedin vivoenvironment

“…Similar studies in the literature have reported binding of DOX ionically to negatively charged groups, for example negatively charged hydrogels and microgels, and a significant increase in release kinetics was observed in acidic pH. [26,27] A slightly higher DOX release was observed from functionalized electrospun fibers even with PVA hydrogels containing no acid. This could be attributed to the fact that a 5% solution of PVA exhibits a pH in the range of 5.0-6.5 [28] that could lead to lower pH of the fluid in the vicinity of scaffolds as compared to fluid at physiological pH.…”

Application of guanidine-containing polymers for preparation of pH responsive silica-based particles for drug delivery systems

“…Also Mahrokh Dadsetan at el reported about preparation of pH-responsive microgels based on a copolymer of oligo(polyethylene glycol) fumarate and sodium methacrylate. Such microgels are capable of loading 67 mol/g of doxorubicin [40].…”

Synthesis, Characterization and Swelling study of Poly (Methacrylic acid-co-Maleic acid) Hydrogels

“…These materials are of great interest since they find several applications as separation membranes 5 , sensors 6 , adsorbents, medical and pharmaceutical drug delivery systems, as well as in other various nanotechnology fields [7][8][9] .…”