Ionic co-aggregates based intravenous drug delivery: Evaluation on kinetics and distribution of the drug payloads and nanocarriers.

Surfactants are crucial in formulating poorly soluble drugs but lead to serious side effects due to PEG chains. Novel supra-amphiphiles consisting of fatty acids and choline are developed, which spontaneously form ionic co-aggregates (ICAs) in water and exhibit strong solubilizing capacity. Paclitaxel (PTX) is adopted as a model drug here to evaluate the feasibility of choline oleate-based ICAs in the intravenous delivery of poorly soluble drugs by comparing the kinetics and distribution of payloads and nanocarriers. Choline oleate presents a maximum 10-fold enhancement in solubilizing capacity to PTX than Cremophor EL (CreEL), enabling a one-tenth use level in the formulation. Aggregation-caused quenching probes are utilized to evaluate the kinetics and biodistribution of ICAs or CreEL-based micelles (MCs). A huge gap is found between the pharmacokinetic and particokinetic curves of either nanocarrier, indicating fast leakage. ICAs lead to faster PTX leakage in blood circulation but higher PTX distribution to organs than MCs. MCs present a longer circulation in blood but a slower distribution to organs than ICAs. ICAs do not arise adverse reactions in rats following repeated injections, while MCs cause pathological changes in varying degrees. In conclusion, choline oleate-based ICAs provide an alternative to surfactants in formulating poorly soluble drugs.