TY - JOUR

T1 - A competent bidrug loaded water soluble chitosan derivative for the effective inhibition of breast cancer

AU - Nivethaa, E A K

AU - Baskar, S

AU - Martin, Catherine Ann

AU - Ramana, Ramya J

AU - Stephen, A

AU - Narayanan, V

AU - Lakshmi, B S

AU - Frank-Kamenetskaya, Olga V.

AU - Radhakrishnan, Subathra

AU - Narayana, Kalkura S.

PY - 2020/3/4

Y1 - 2020/3/4

N2 - Drug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at –NH2 and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.

AB - Drug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at –NH2 and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.

KW - Breast Neoplasms/pathology

KW - Chitosan/analogs & derivatives

KW - Doxorubicin/chemistry

KW - Drug Carriers/chemistry

KW - Drug Liberation

KW - Fluorouracil/chemistry

KW - Humans

KW - Inhibitory Concentration 50

KW - MCF-7 Cells

KW - Solubility

KW - Water/chemistry

UR - http://www.scopus.com/inward/record.url?scp=85081198433&partnerID=8YFLogxK

U2 - 10.1038/s41598-020-60888-5

DO - 10.1038/s41598-020-60888-5

M3 - Article

C2 - 32132583

AN - SCOPUS:85081198433

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 3991

ER -