Molecular Microencapsulation: Paclitaxel Formations in Aqueous Medium Using Hydrophobized Poly(L-Lysine Citramide Imide)

Hydrophobized polyelectrolytes are able to aggregate in aqueous media and to form lipophilic microdomains which are much more stable than micelles made of amphiphilic diblock copolymers. Solubilization of paclitaxel in water by molecular encapsulation was attempted in the hydrophobic pockets present in the aggregates of hydrophobized poly(l-lysine citramide imide) polymers, PLCAi _x R _y , where x = percentage in imide groups and y = percentage in alkyl substituents per lysine citramide repeat unit. A comparison was made of the physical entrapment and the solubilization of paclitaxel in PLCAi ₂₇ C12 ₃₄ , PLCAC12 ₇₅ , PLCAi ₁₃ C7 ₃₀ , PLCAC12 ₁₀₀ aggregates and in the usual allergic Cremophor® present in the Taxol® commercial formulation. PLCAi _x R _y polymers solubilized paclitaxel in the selected aqueous medium proportionally to the polymer concentration. For comparable amounts in weight, the polymers were two to six times less efficient than Cremophor® in terms of equivalent mass of solubilizing species. A comparison between PLCAi ₁₃ C7 ₃₀ and PLCAi _x C12 _y polymers suggested that dodecyl hydrophobizing groups were more efficient than heptyl ones in promoting the physical entrapment of paclitaxel. The antitumoral activity of the polymer-solubilized paclitaxel was tested in vitro against an ovarian carcinoma cell line (A2780). The C12 systems showed cytotoxicity, the IC ₅₀ values were statistically comparable in the 6.5-10.5 μg/L range. However, the amounts of drug incorporated in the polymer aggregates at the tested concentrations were still too low for clinical use. Improvements are expected from PLCA polymers with longer alkyl chains, greater hydrophobicity and higher concentrations.