Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC)

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 153; pp. 208 - 219
• Main Authors: Godugu, Chandraiah, Doddapaneni, Ravi, Singh, Mandip
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2017
• Subjects: Administration, Oral; Animals; Anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Bioavailability; Biological Availability; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - chemistry; Biphenyl Compounds - pharmacology; Caco-2 Cells; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Female; Honokiol; Humans; Lignans - administration & dosage; Lignans - chemistry; Lignans - pharmacology; Male; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Micelles; Nanomicellar formulation; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Particle Size; Structure-Activity Relationship; Surface Properties; TNBC; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Honokiol; Bioavailability; Anticancer; TNBC; Nanomicellar formulation
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2017.01.038

[Display omitted] •First study on oral Honokiol nanomicellar (NM) formulation for therapy of TNBC.•Honokiol NM formulation produced superior Pharmacokinetic and Pharmacodynamic properties.•NM formulation produced better oral bioavailability even at one fourth of the free drug dose.•25% of animals were found to be free from tumors 4 weeks after NM treatment. 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.