CAGE ionic liquid-mediated co-solubilization of lapatinib and resveratrol enhances cytotoxicity in lung cancer cells with uniform aerosolization for pulmonary delivery.

Authors

Nidhi Singh, Kolimi Prasanth Reddy, Rudra Chakravarti, Navratan Soni, David Paul, Dipanjan Ghosh, Pallab Datta

Published in

Journal of pharmaceutical sciences. Pages 104534. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

Choline and geranic acid-based ionic liquids (CAGE-IL) have emerged as powerful delivery vehicles for many challenging drug molecules via different routes of administration. However, their potential for aerosol delivery has not been reported. In this study, CAGE-IL is investigated for its ability to solubilise a combination of lapatinib ditosylate (LPT) and resveratrol (RSV) as a potential vehicle for localised delivery in lung cancer therapy. The results showed that CAGE-IL had much higher solubility for LPT (114.6 ± 3.5 mg/mL vs. 0.02 mg/mL) and RSV (58.1 ± 6.8 mg/mL vs. 0.03 mg/mL) than their respective aqueous solubilities, as determined using a validated HPLC method developed for the simultaneous estimation of the molecules. An octanol/water partition coefficient of 2.34 for LPT from LPT-CAGE-IL and 2.18 for RSV from RSV-CAGE-IL was obtained. Upon evaluation in A549, a lung adenocarcinoma cell line, the IC₅₀ value of LPT+RSV-co-loaded CAGE-IL was significantly lower (1.2 times, p˂0.006) than LPT solution (5.3 times, p˂0.0001) or RSV solution (2.7 times, p˂0.001). Importantly, we performed the first nebulization efficiency characterisation for CAGE-IL, obtaining 48 ± 1% for LPT and 49 ± 1% for RSV, with drug output rates of 15 mg/min for LPT and 7 mg/min for RSV and D₅₀ of 2.74 µm. The MMAD, FPF, and GSD were 2.00 ± 0.2 µm, 74 ± 5 %, and 2.48 ± 0.2 for RSV, and 2.10 ± 0.3 µm, 70 ± 7 %, and 2.87 ± 0.2 for LPT showing the suitability of the prepared formulation for pulmonary use. Overall, achieving high solubility of both drugs in a single medium, along with near-identical recovery, signified uniform co-aerosolisation without phase separation during nebulization, indicating CAGE-IL as a possible vehicle for inhalation delivery, and enhance the therapeutic efficacy for localised lung cancer treatment.

PMID:
42843560
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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