Molecular microencapsulation: Paclitaxel formations in aqueous medium using hydrophobized poly(L-lysine citramide imide)

Hydrophobized polyelectrolytes are able to aggregate in aqueous media and t o form lipophilic microdomains which are much more stable than micelles mad e 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(R) present in the Taxol(R) commercial formaulation . PLCAi(x)R(y) polymers solubilized paclitaxel in the selected aqueous medi um proportionally to the polymer concentration. For comparable amounts in w eight, the polymers were two to six times less efficient than Cremophor(R) in terms of equivalent mass of solubilizing species. A comparison between P LCAi(13)C7(30) and PLCAi(x)C12(y) polymers suggested that dodecyl hydrophob izing groups were more efficient than heptyl ones in promoting the physical entrapment of paclitaxel. The antitumoral activity of the polymer-solubili zed paclitaxel was tested in vitro against an ovarian carcinoma cell line ( A2780). The C12 systems showed cytotoxicity, the IC50 values were statistic ally comparable in the 6.5-10.5 mu g/L range. However, the amounts of drug incorporated in the polymer aggregates at the tested concentrations were st ill too low for clinical use. Improvements are expected from PLCA polymers with longer alkyl chains, greater hydrophobicity and higher concentrations.