Nanomedicine Journal

Nanomedicine Journal

Development and physicochemical characterisation of a cremophor-free paclitaxel–calix[6]arene inclusion complex with increased apparent solubility and in vitro cytotoxicity in mia-pa-ca-2 pancreatic cancer cells

Articles in Press

Document Type : Research Paper

Authors
Bina Gidwani 1
Jyoti Sahu 2, 3
Sanjay Kumar Gupta 4
1 Columbia Institute of Pharmacy, Faculty of Pharmacy, Columbia Professional University, Raipur, Chhattisgarh, India
2 Shri Rawatpura Sarkar Institute of Pharmacy, Durg, Chhattisgarh, India
3 Vishwakarma University, School of Pharmacy, Pune, Chhattisgarh, India
4 Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Rungta International Skills University, Bhilai, Durg, Chhattisgarh, India
10.22038/nmj.2026.93642.2378
Abstract
Objective(s): The current research focused on the development of a Cremophor-free Paclitaxel (PTX)–Calix[6]arene (C6A) inclusion complex. To determine its apparent aqueous solubility and in vitro cytotoxicity against MIA-Pa-Ca-2 pancreatic cancer cells.
Materials and Methods: An optimised PTX–C6A inclusion complex (3:5 mole ratio) was synthesised through physical mixing, and the drug loading was estimated using a validated HPLC technique. The physical characterisation of the inclusion complex was performed using FTIR, DSC, XRD, FESEM, and EDX techniques. The aqueous solubility of the complexes was comparatively studied at pH 6.8 and 7.4 using the UV-visible spectrophotometer technique, and their cytotoxicity in vitro against the MIA-Pa-Ca-2 cell line was evaluated.
Results: The optimised 3:5 inclusion complex (IC) showed 84.7 ± 0.2 % (n=3) drug content, which was calculated using the HPLC technique. The inclusion complex exhibited higher apparent aqueous solubility than free PTX at both pH 6.8 and 7.4, with a more pronounced enhancement at pH 6.8. XRD analysis suggested partial amorphisation of the inclusion complex, while FESEM examination revealed predominantly spherical particles with diameters ranging from approximately 45–60 nm. The FTIR spectra showed no significant variation in the characteristic absorption bands after 12 weeks of storage, indicating no detectable changes in the characteristic FTIR profile during storage. In addition, the inclusion complex showed in vitro cytotoxic activity against MIA-Pa-Ca-2 cells with an IC50 of 5.641 nM, which was better than that of PTX (6.705 nM) and C6A (9.498 nM).
Conclusion: The apparent aqueous solubility of the PTX–C6A inclusion complex was slightly higher than that of PTX, accompanied by partial amorphisation of PTX. It also showed higher in vitro cytotoxic activity against MIA-Pa-Ca-2 cells as compared to free PTX. The overall anticancer activity of the inclusion complex could be affected by the intrinsic cytotoxicity of Calix[6]arene; however, further investigation is needed to confirm this contribution.
Keywords
Calix[6]arene
Cremophor&ndash
free formulation
Paclitaxel
Pancreatic cancer
Supramolecular chemistry
Subjects
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Nanomedicine Journal

Articles in Press, Accepted Manuscript
Available Online from 23 September 2026