Telmisartan-poly (ethylene glycol) conjugate augmented drug dissolution and permeability in cervical cancer cells
Telmisartan is currently reported for inhibiting cervical cancer cells. Despite favorable therapeutic profile, poor aqueous solubility and low oral bioavailability limit its therapeutic application in treatment of cervical cancer. Telmisartan was chemically conjugated to poly (ethylene glycol) through amide linkage to form telmisartan-PEG drug conjugate. Poly (ethylene glycol) with terminal –NH2 was conjugated with telmisartan via amide linkage. Telmisartan-PEG conjugate displayed peak at 1690 cm-1 for C=O group of amide linkage. Furthermore, telmisartan illustrated the crystalline lattice as compared to amorphous nature of telmisartan-PEG conjugate. The in vitro dissolution testing indicated that telmisartan displayed only 22.6±3.8% drug release from dialysis bag as compared (Two-way ANOVA test, P<0.05) to 76.9±5.4% from telmisartan-PEG conjugate. The therapeutic efficacy of telmisartan and telmisartan-PEG conjugate was analyzed in cervical cancer, HeLa cells. The IC50 of telmisartan in HeLa cells was estimated to be 48.6±6.9µM as compared (Two Way ANOVA test) to 17.2±2.7-µM of telmisartan-PEG conjugate dissolved in aqueous phase. In conclusion, telmisartan-PEG conjugate must be investigated under a set of stringent in vivo parameters for pharmacokinetic and pharmacodynamic studies.
Keywords: Cervical cancer, telmisartan, poly (ethylene glycol), conjugate, dissolution, cytotoxicity
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