Abstract
Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, ω-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4′-chloro-3′-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI < 0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.
Highlights
Breast cancer is the most common type of cancer among women worldwide after non-melanoma skin cancer, affecting more than 200,000 women annually and killing more than 40,000 women each year
Of the six compositions and phase combinations investigated, only the phase inversion emulsification process P2, in which the water phase was added to the oily phase containing both surfactants, provided a stable nanoemulsion with an average droplet size and polydispersity index (PDI) over 3 months of 130.9 ± 19.8 nm and 0.146 ± 0.02, respectively
Nanotechnologies have been often applied the administration of existing anticancer drugs, with the aim to modify their pharmacokinetics, improve their efficacy, and reduce drug-related adverse effects
Summary
Breast cancer is the most common type of cancer among women worldwide after non-melanoma skin cancer, affecting more than 200,000 women annually and killing more than 40,000 women each year. Breast cancer affects men, but it is rare, accounting for only 1% of all cases of cancer. Statistics indicate an increasing incidence in both developed and developing countries. There are several types of breast cancer, and their characteristics affect both treatment options. Triple-negative breast cancer (TBNC), i.e., tumors that lack expression orefcTteeehshspteterrtroraooegprgeaeentruynetpriscereecevoec2eupertt(pacoHlotromtEy(rREep(sR2eE.s))R,,Toar)pfi,rrpbeoplregrea-eoagnssgegtteegrcrsaeoattsnneisvcreieoevrrneb,eercaaeenrnapdesdtctotehrhcpeai(itgnProchRcrel)hry,(aP(armTRasBce)twN,tearaeCislss)ltt,awiactis.sieec.lah,,lfuaftaeumnscmdtahnboduorsoemthptnaihtdonraeettraemrltpaemacsidelkpnegoetrrnxmoopdpwratettilhososgniefrsoanoncawdtnooodtrfhcrifnaectoorr mornecoecpltoonratlypaent2ib(HodEiRe2s)-,baarseeadgtghreesrsaipveieasn. DThhiugsh,lypamtieetnasttsawtici,thanTdNdBoCnohtarveseploimnditteodetnrdeoactmrineenot roptions, andmosnuobcsleoqnualeannttliyb,oadpieos-obraesredprtohgernaopsieiss.[T1]h.uIst, ipsaktinenotws nwitthhaTt NduBCrinhgavtehelimdeitvedeltorpeamtmenenttoofpbtrioenass,t cancer sevaenrdalsurebgseuqluaetontrlyy,ma epcohoarenrispmrosganroesiisn[1im]. LTohpeadnetivcealnopcemretnhteoraf peutics ablctaehogemetMronaptapisonn.euduynutdiscctsseuwadfuibitelhretshnthooeavrivenrleedmmureceicecsehsfinauontrnlityshsmeeirnsvroicdefameanncicstceisoeriondpnaaasgtriaineeinnlacstattsintowucnemhrsoohpriaapctreieebllnerstetsawsriwesetehraenonqtpuartioreoleydreeuststnoiassbdtaaletnivustehrlteaoodtpeedaasntgafteabincltaittsynsh.ceaedcrids and cancer.MIannyfasctut,dωies-6hapvoelyreucnenstaltyuervaitdeedncfeadttay raeclaidtiosn(sPhUipFbAestw) eaerne pcoolnyvuenrstaetudrabtyedtufamttyoraccidelslsantdo potent eiccoasnacnero.idInpfraoctm, ωot-e6rpsoolyfutnusmatourracteedll fpatrtoyliafecirdasti(oPnUFthArso)uagrhe ctohnevoervteedr-ebxyptruemssoironceollfs ctoycplootoexnyt genase, lipeoixcoysgaennoaidseproormcoytteorschorfotmume oPr4c5e0ll epnrzoylimfereast.ionInthcroonutgrhastth,eseoverr-aelxpericeosssiaonooidf cmycelotaobxyoglietneassefr, om the biolitpraonxysgfoernmasaetioorncoyftoωch-r3oPmUe FPA45s0imenpzayimr pesa.rtInicucolanrtrtausmt, oservigeeranliceipcoastahnwoaidysm, ientadbioclaiteins gfrtohmattthhee intake of bωio-t3rapnsofloyrumnastaiotnuroaftωed-3 fPaUttFyAas cimidpsamir pigahrtticduelacrretuamseorciagnenciecrpraitshkw, aiyns,pinadrtiiccautilnagr tfhoart tbhreeianstta,kpe rostate, andof ωco-3lopnolcyaunncsaetrur[a5t,e6d].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.