Shell Cross‐Linked Polymeric Micelles as Camptothecin Nanocarriers for Anti‐HCV Therapy

Abstract

A suitable carrier for camptothecin to act as therapy against the hepatitis C virus is presented. The carrier relies on an amphiphilic hybrid dendritic-linear-dendritic block copolymer, derived from pluronic F127 and bis-MPA dendrons, that forms micelles in aqueous solution. The dendrons admit the incorporation of multiple photoreactive groups that allow the clean and effective preparation of covalently cross-linked polymeric micelles (CLPM), susceptible of loading hydrophilic and lipophilic molecules. Cell-uptake experiments using a newly designed fluorophore, derived from rhodamine B, demonstrate that the carrier favors the accumulation of its cargo within the cell. Furthermore, loaded with camptothecin, it is efficient in fighting against the hepatitis C virus while shows lower cytotoxicity than the free drug.

Micelle carriers based on dendritic macromolecules containing bis-MPA and glycine for antimalarial drug delivery

“…HDLDBC-bGMPA nanocarriers were labeled by encapsulating a low water soluble modified rhodamine B (Rho(C17) 2 ) red fluorophore previously reported by us, 27 and the oil-in-water procedure was employed to encapsulate the fluorophore within the nanocarrier. The selected feeding ratio in this case was (1 : 0.15) (w HDLDBC : w Rho ).…”

“…25 HDLDBC-bGMPA nanocarriers were labeled by encapsulating a lipophilic modified rhodamine B (Rho(C17) 2 ) red fluorophore, using the oilin-water procedure as previously reported by us. 27 In order to check the stability of this labeling, Rho(C17) 2 release from the HDLDBC-bGMPA/Rho(C17) 2 conjugates was studied by dialysis. Unmodified water-soluble rhodamine B fluorophore was encapsulated within HDLDBC-bGMPA micelles following the same protocol, to be used as a control.…”

Crosslinked polymeric self-assemblies as an efficient strategy for photodynamic therapy on a 3D cell culture

“…This might be attributed to a retention effect of the drug by the crosslinked micelle as shown in different publications. 16,17,19,25,34,38,45 One has to keep in mind that the dialysis results presented above were performed in pure water and at a Pheo concentration of 1 mM, and indicated only a slightly lower release rate for chain-end polymerized micelles and an identical one for crosslinked systems. This conguration is similar to the 50 mM polymer concentration in phototoxicity experiment (Fig.…”

“…Several strategies have been evaluated, namely crosslinking of the shell, of the core or at the interface between hydrophobic/ hydrophilic zones. 12,13 Even if the subject has been studied for over 15 years, new cases are still being published, with different crosslinking methods, such as radical reactions, [14][15][16][17] reversible disulde bonds, [18][19][20][21][22][23][24] or coupling reactions. [25][26][27][28][29][30][31][32][33][34][35][36] Original approaches have used uracyl moieties, 37 dopamine oxidation in the presence of air 38 or cinnamate reversible dimerization.…”

“…This almost always leads to a lower activity of the drug compared to the free one or to its form encapsulated in an uncrosslinked vector. 16,17,19,25,34,38,45 Only in a few cases are activities on the same range or even better. 20,26,31,35,41 In a general manner, in vivo studies remain seldom, although moving away from 2D cell culture is increasingly shown to be essential for a better development of future therapeutics.…”