title: Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC).
abstract: Triple negative breast cancer (TNBC), owing to its aggressive behavior and toxicity associated with available chemotherapy; currently no suitable therapy is available. Honokiol (HNK) is a promising anticancer drug but has poor bioavailability. In the current study, we evaluated the anticancer effects of an oral Honokiol nanomicellar (NM) formulation (size range of 20-40nm) in vitro against various TNBC cells lines. Cytotoxicity, clonogenic and wound healing assays demonstrated the promising anticancer effects. In vitro Caco-2 permeability studies suggested increased absorption of Honokiol. Compared to HNK-FD, nanomicellar formulations resulted in significant increase in the oral bioavailability. Cmax(4.06 and 3.60-fold) and AUC (6.26 and 5.83-fold) were significantly increased in comparison to oral 40 and 80mg/kg free drug respectively. Further, anticancer effects of these formulations were studied in BALB/c nude mice transplanted with orthotopic MDA-MB-231 cell induced xenografts. After 4 weeks of daily administration of HNK-NM formulation, significant reduction in the tumor volumes and weights compared to free drug (p<0.001) treated groups was observed. Surprisingly, in some of the animals (25%), the treatment resulted in complete eradication of tumors. Increased apoptosis and antiangiogenic effect was observed in HNK-NM groups compared to free drug and untreated control animals. This is the first report demonstrating that HNK-FD possesses anticancer effects against TNBC.
authors.affiliation: College of Pharmacy Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad, Telangana 500037 India.
authors.forename: Chandraiah
authors.initials: C
authors.lastname: Godugu
authors.affiliation: College of Pharmacy Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA; Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Doddapaneni
authors.affiliation: College of Pharmacy Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA. Electronic address: mandip.sachdeva@gmail.com.
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017705:Lignans / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D017705:Lignans; D008823:Micelles; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Anticancer; Bioavailability; Honokiol; Nanomicellar formulation; TNBC