title: Inhalable bioresponsive chitosan microspheres of doxorubicin and soluble curcumin augmented drug delivery in lung cancer cells.
abstract: In present investigation, doxorubicin (Dox) and soluble curcumin (Cur-2-HP-β-CD-complex) combination was simultaneously loaded in inhalable bioresponsive chitosan microspheres (Dox/Cur-2-HP-β-CD-complex-elastin-CMs) bearing a substrate-stimuli, elastin. The mean particle size and mean aerodynamic diameter of inhalable bioresponsive microspheres displayed noteworthy differences after incorporation of elastin. Moreover, combination of Dox and soluble curcumin was molecularly dispersed in microspheres matrix as substantiated by a range of spectral techniques. Inhalable bioresponsive microspheres released astonishingly higher amount of Dox in presence of elastase enzyme at pH∼5.5 in comparison to pH∼7.4. However, the release of soluble curcumin from tailored bioresponsive microspheres in presence of elastase enzyme was independent of pH. Consistently, inhalable bioresponsive microspheres exhibited outstandingly lower IC50of 3.4-μM in comparison to 6.5-μM of inhalable drug loaded microspheres (Dox/Cur-2-HP-β-CD-complex-CMs) bearing no elastin, against A549, non-small cell lung cancer cells. The superior therapeutic profile of inhalable bioresponsive microspheres may be attributed to enhanced drug release and consequently augmented drug exposure to A549 cells expressing elastase enzyme. In this way, stimuli triggered drug release from tailored inhalable bioresponsive microspheres boosted the phenomena of apoptosis in A549 cells. In conclusion, Dox/Cur-2-HP-β-CD-complex-elastin-CMs warrant further in-vivo tumor regression study to prove its therapeutic efficacy.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Jyoti
authors.affiliation: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Kush
authors.affiliation: Department of Pharmaceutics, Hindu College of Pharmacy, Sonepat, Haryana, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000072283:A549 Cells; D000280:Administration, Inhalation; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D004549:Elastin / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000473:pathology*; D008863:Microspheres; D010316:Particle Size; D012995:Solubility
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin; D004549:Elastin; D048271:Chitosan; D003474:Curcumin
keywords: Bioresponsive; Doxorubicin; Elastin; Inhalable microspheres; Non-small cell lung cancer cells; Soluble curcumin