Physicochemical aspects of doxorubicin-loaded pH-sensitive polymeric micelle formulations from a mixture of poly(l-histidine)-b-poly(l-lactide)-b-poly(ethylene glycol)

Abstract

In this study, doxorubicin (DOX) was physically incorporated into pH sensitive micelles made from a mixture of poly(L--Histidine)-b-poly(ethylene glycol)/ poly(L--Lactide)-b-poly(ethylene glycol) (75/25, wt.%). The DOX-loaded mixed micelles were formulated using dialysis methods and optimal DOX incorporation was achieved at a drug/polymer feed ratio of 0.2 (wt./wt.) when proper amount of aqueous phase (0.2, v./v.) was added into the common solvent (DMSO) solution, followed by dialysis at 4°C. Based on the results obtained from dynamic light scattering, UV-Vis absorption, and fluorescence experiments, it was demonstrated that the encapsulated drugs were mainly located inside the hydrophobic micelle cores, well protected and inaccessible to exterior molecules. Under in vitro conditions, although the microstructure of the micelles was altered below pH 8.0 by the encapsulated drugs, the drug-loaded micelles still exhibited desirable ability to control the drug release in response to tumor extracellular pH.

Terminal modification of polymeric micelles with π-conjugated moieties for efficient anticancer drug delivery

“…The π-π stacking interaction within the drug loaded micelles was tested by fluorescence spectra and UV-vis absorption ( Figure 4). It is well-known that the DOX has a characteristic chromophore composed of aromatic structure, which would be used to monitor the interaction with other molecules [35].…”

Polymeric micelles: authoritative aspects for drug delivery

“…Micelles can also be taken up into the cell by the process of endocytosis and may as well enter cell organelles as endosomes, lysosomes, etc. The pH value inside these organelles is nearly 5.5 [91].…”

pH-sensitive drug-delivery Systems for Tumor Targeting

“…While at endosomal/lysosomal pH, they could be protonated, yielding a transition from hydrophilic to hydrophobic, resulting in destabilization of the derived vehicles. Poly(N,N´-dimethyl aminoethyl methacrylate), PAE, poly(4-vinylpyridine) and poly(histidine) [84][85][86], which contain tertiary amine groups or pyridine groups could be protonated as pH decreases, undergoing phase transition from hydrophobic to hydrophilic, inducing endosomal/lysosomal drug release. Kim et al successfully constructed a pH-sensitive micelle utilizing poly(l-histidine)-b-PEG-folate or polyHis-b-PEG blended with poly(lactic acid) (PLLA)-b-PEG-folate [87,88].…”