Telmisartan complex augments solubility, dissolution and drug delivery in prostate cancer cells

• Published in: Carbohydrate polymers 2014-01, Vol.101, p.614-622
• Main Authors: Kaur, Manveet, Bhatia, Richa Kaur, Pissurlenkar, Raghuvir R.S., Coutinho, Evans C., Jain, Upendra Kumar, Katare, Om Prakash, Chandra, Ramesh, Madan, Jitender
• Format: Article
• Language: English
• Subjects: 2-HP-β-CD; 2-Hydroxypropyl-beta-cyclodextrin; Applied sciences; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Benzoates - chemistry; Benzoates - pharmacology; beta-Cyclodextrins - chemistry; Biological and medical sciences; Cell Line, Tumor; Complex; Computer Simulation; Cytotoxicity; Drug Carriers - chemistry; Exact sciences and technology; General pharmacology; Humans; In silico docking; Male; Medical sciences; Models, Molecular; Molecular Conformation; Natural polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Prostatic Neoplasms - pathology; Solubility; Starch and polysaccharides; Telmisartan
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2013.09.077

•Telmisartan inhibits the growth of prostate cancer cells with low therapeutic index.•We have synthesized a complex of telmisartan using the carbohydrate polymer, 2-HP-β-CD to augment solubility, dissolution and cytotoxicity in prostate cancer cells.•The encapsulation of telmisartan in the 2-HP-β-CD cavity was confirmed in at least two orientations with equal binding energies.•The complex exhibited its superiority in both in vitro release and cytotoxicity experiments.•Our studies warrant an in vivo study to scale-up the technology for clinical translation. Telmisartan (TEL) requires superior bioavailability in cancer cell compartments. To meet these challenges, we have synthesized a 2-HP-β-CD-TEL complex with stability constant (Kc) of 2.39×10−3mM. The absence in the FTIR spectrum of 2-HP-β-CD-TEL complex of the characteristic peaks of TEL at 1699cm−1 (carboxylic acid) and 741 and 756cm−1 (1,2-disubstituted benzene ring vibrations), is indicative of the encapsulation of TEL in the 2-HP-β-CD cavity. DSC and PXRD also confirmed the synthesis and amorphous structure of complex. The interaction of TEL with 2-HP-β-CD was examined by NMR and 2D-ROESY which affirms the encapsulation of TEL in the 2-HP-β-CD cavity in at least two orientations with equal binding energies. The complex also exhibited its superiority in both in vitro release and cytotoxicity experiments on prostate cancer, PC-3 cells as compared to free drug. These data warrant an in depth in vivo to scale-up the technology for the management of prostate cancer.