Incorporation of anticancer drugs with low lipophilicity in lipid nanocarriers is usually low, which limits the utilization of this strategy in cancer therapy. However, the complexation of these drugs with lipophilic ion pairs containing ionizable groups has been reported to improve their incorporation in nanocarriers such as solid lipid nanoparticles (SLNs), nanostructured lipid nanocarriers (NLCs), and nanoemulsions (NEs). Therefore, those nanocarriers have shown an increase in efficacy and lower toxicity compared with the free drugs, particularly if the counter ion utilized has anticancer activity. Areas covered: This review covers, from 1999 to the present, the utilization of the hydrophobic ion pair (HIP) approach to enhance the encapsulation of anticancer drugs in lipid nanostructured delivery systems, SLN, NLC, and NE; the benefits achieved; and challenges to improve the anticancer therapy. Expert opinion: The HIP strategy has consistently demonstrated enhancement of the encapsulation efficiency in NLCs associated with increased anticancer activity of drugs such as doxorubicin, all-trans retinoic acid, methotrexate, vincristine and others. From this point on, conducting further physicochemical characterization studies of the formed ion pair as well as proceeding with the in vivo efficacy, toxicity and pharmacokinetics studies are expected.
Keywords: Anticancer effect; antineoplastic drugs; cancer; encapsulation; hydrophobic ion pairing; lipid nanocarriers.