Micellar Nanocarriers Assembled from Doxorubicin‐Conjugated Amphiphilic Macromolecules (DOX–AM)

Abstract

Amphiphilic macromolecules (AMs) have unique branched hydrophobic domains attached to linear PEG chains. AMs self-assemble in aqueous solution to form micelles that are hydrolytically stable in physiological conditions (37 degrees C, pH 7.4) over 4 weeks. Evidence of AM biodegradability was demonstrated by complete AM degradation after 6 d in the presence of lipase. Doxorubicin (DOX) was chemically conjugated to AMs via a hydrazone linker to form DOX-AM conjugates that self-assembled into micelles in aqueous solution. The conjugates were compared with DOX-loaded AM micelles (i.e., physically loaded DOX) on DOX content, micellar sizes and in vitro cytotoxicity. Physically encapsulated DOX loading was higher (12 wt.-%) than chemically bound DOX (6 wt.-%), and micellar sizes of DOX-loaded AMs (approximately 16 nm) were smaller than DOX-AMs (approximately 30 nm). In vitro DOX release from DOX-AM conjugates was faster at pH 5.0 (100%) compared to pH 7.4 (78%) after 48 h, 37 degrees C. Compared to free DOX and physically encapsulated DOX, chemically bound DOX had significantly higher cytotoxicity at 10(-7) M DOX dose against human hepatocellular carcinoma cells after 72 h. Overall, DOX-AM micelles showed promising characteristics as stable, biodegradable DOX nanocarriers.

Templating Synthesis of Preloaded Doxorubicin in Hollow Mesoporous Silica Nanospheres for Biomedical Applications

“…The results clearly reveal the activity of DOX with the mechanisms of killing tumor cells by DNA damage and topoisomerase II inhibition. [ 16 ] Thus, active preloading of DOX in HMS@DOX can be proved. The therapeutic effect of HMS@DOX and the release of DOX at pH 7.4 at predetermined time points exhibit a similar trend before 8 h ( Figure 2B ).…”

Development of Disulfide Core‐Crosslinked Pluronic Nanoparticles as an Effective Anticancer‐Drug‐Delivery System

“…[4,5] These carriers enhance the water solubility and stability of drugs, prolong the circulation time in the blood and accumulate drugs by the enhanced permeability and retention effect (EPR) at the cancerous tissue. [6][7][8] Because of the need for technologically biodegradable smart materials for use in drug delivery, a number of polymers have been developed by extensively investigating various stimuli sensitivities, such as pH, light, temperature and redox potentials. [9][10][11][12] Although most anticancer drugs are hydrophobic, selfassembly of amphiphilic molecules in aqueous media is of fundamental interest in overcoming the problems associated with effective anticancer-drug delivery.…”

Designing polymers with sugar-based advantages for bioactive delivery applications

“…As the pH of different cellular compartments varies, polymer systems with acid-labile bonds or protonatable functionalities can be utilized to facilitate endosomal drug release by increasing hydrolysis rates [130] or changing the polymer protonation [94]. Several sugars have pKa values close to physiological conditions, such as chitosan.…”