Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles.
Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPβCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPβCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and1H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.
a Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
Amrita
A
Kadari
a Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
Sagarika
S
Gudem
a Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
Hitesh
H
Kulhari
b National Centre for Mass Spectrometry, Indian Institute of Chemical Technology , Hyderabad , India , and.
Murali Mohan
MM
Bhandi
b National Centre for Mass Spectrometry, Indian Institute of Chemical Technology , Hyderabad , India , and.
Roshan M
RM
Borkar
c Department of Pharmaceutical Sciences , A.U. College of Pharmaceutical Sciences, Andhra University , Visakhapatnam , India.
Venkata Ramana Murthy
VR
Kolapalli
a Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
Ramakrishna
R
Sistla
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D005260:Female; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D005419:Flavonoids; D044948:Flavonols; D011108:Polymers; D017382:Reactive Oxygen Species; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C017875:fisetin
Fisetin; PLGA nanoparticles; anticancer activity; hyroxypropyl β-cyclodextrin; inclusion complex; oral bioavailability