Comparison Between Interaction of Hydrophobic-anionic and Hydrophobic-cationic Mixed Micellar System with Drug Ciprofloxacin

The interaction studies of drug ciprofloxacin with two mixed micellar systems are reported. The mixed micelles comprise a nonionic hydrophobic surfactant, pluronic L-81, an anionic surfactant, Ammonium dodecyl sulfate (ADS); and a cationic surfactant, Cetylpyridinium bromide (CPB). The various combinations chosen were L-81-ADS and L-81-CPB. The properties of both the mixed micelles were compared. Spectrophotometric, conductometric, co-solvent effect, and Infrared studies were used for the investigations. The studies were carried out in a wide range of mixed micellar concentrations in the post micellar region of the individual surfactants. The solubilization of drug CPX in the L-81-ADS was higher than that in L-81-CPB mixed micelle, as evidenced by UV studies. Ethanol and ethylene glycol were found to be effective co-solvents for both the mixed micellar systems. The conductivity studies of CPX with ADS and CPB surfactants, displayed a higher value of conductance for CPX and ADS, from 0.37µs-1 to 0.74µs-1 compared to CPX and CPB. The drug-mixed micelle displayed a higher molecular weight complex formation as seen from the IR spectra.

Doxorubicin-Loaded Mixed Micelles Using Degradable Graft and Diblock Copolymers to Enhance Anticancer Sensitivity

In this study, a graft copolymer, poly(N-(2-hydroxypropyl) methacrylamide dilactate)-co-(N-(2-hydroxypropyl) methacrylamide-co-histidine)-graft-poly(d,l-lactide), and a diblock copolymer, methoxy poly(ethylene glycol)-b-poly(d,l-lactide), were assembled into a mixed micellar system to encapsulate the anticancer drug doxorubicin (Dox). This mixed micellar system possesses the hydrophobic lactide segment of both copolymers, which reinforces its stability in physiological milieus; the histidine molecules appended on the graft copolymer provide the desired pH-responsive behavior to release Dox during internalization in cancer cells. The results demonstrate that the two copolymers were successfully prepared, and their ratios in the mixed micelles were optimized on the basis of the results of the stability tests. Under acidic conditions, the mixed micelles swell and are able to release their payloads. Therefore, the in vitro results indicate that the Dox in the mixed micelles is released effectively in response to the environmental pH of the mimetic internalization process, increasing cancer cells’ sensitivity toward Dox. The mixed micelles display low cytotoxicity due to the degradability of the polymers. The in vivo images show that the high stability of the mixed micelles ensures a high tumor accumulation. This selective tumor accumulation results in an excellent inhibition of in vivo tumor growth and a high rate of apoptosis in cancerous tissues, with low toxicity. This highly stable, mixed micellar system with a pH-dependent drug release, which enables the precise delivery of drugs to the tumor lesions, is feasible to employ clinically in cancer therapy.

Development of a Rapid-Onset, Acid-Labile Linkage Polyplex-Mixed Micellar System for Anticancer Therapy

In the treatment of cancers, small interfering ribonucleic acids (siRNAs) are delivered into cells to inhibit the oncogenic protein’s expression; however, polyanions, hydrophilicity, and rapid degradations in blood, endosomal or secondary lysosomal degradation hamper clinal applications. In this study, we first synthesized and characterized two copolymers: methoxy poly(ethylene glycol)-b-poly(2-hydroxy methacrylate-ketal-pyridoxal) and methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-histidine). Afterwards, we assembled two polymers with the focal adhesion kinase (FAK) siRNA, forming polyplex-mixed micelles for the treatment of the human colon cancer cell line HCT116. In terms of the physiological condition, the cationic pyridoxal molecules that were conjugated on the copolymer with ketal bonds could electrostatically attract the siRNA. Additionally, the pyridoxal could form a hydrophobic core together with the hydrophobic deprotonated histidine molecules in the other copolymer and the hydrophilic polyethylene glycol (PEG) shell to protect the siRNA. In an acidic condition, the pyridoxal would be cleaved from the polymers due to the breakage of the ketal bonds and the histidine molecules can simultaneously be protonated, resulting in the endosome/lysosome escape effect. On the basis of our results, the two copolymers were successfully prepared and the pyridoxal derivatives were identified to be able to carry the siRNA and be cleavable by the copolymers in an acidic solution. Polyplex-mixed micelles were prepared, and the micellar structures were identified. The endosome escape behavior was observed using a confocal laser scanning microscopy (CLSM). The FAK expression was therefore reduced, and the cytotoxicity of siRNA toward human colon cancer cells was exhibited, rapidly in 24 h. This exceptional anticancer efficiency suggests the potential of the pH-sensitive polyplex-mixed micellar system in siRNA delivery.