Searchingforsafeandeffectivedrugdeliverycarriershasgainedalotofdemandinrecentyears.Thisiswhy naturalcarriersbecomethetargetofresearchersworkinginthatfield.Inthisstudy,buffalo'smilkisinvestigated asanaturallipophiliccarrierforthedeliveryofamodellipophilicdrug,lornoxicam(LOR).LORhasbeenloaded intomilkfatglobulesviahomogenization.Thehomogenizedfatglobulesandcaseinmicelleswerecharacterized fortheirsize,charge,surfacemorphology,andentrapmentefficiencyofLORintofatglobules.AnewHPLC-UV detectionmethodcoupledwithliquid-liquidextraction(LLE)procedurewasdevelopedandfullyvalidatedfor thequantitativedeterminationofLORinfatglobules.Resultsshowedthatdynamiclightscatteringofblankand loadedfatglobuleshadasimilarparticlesizesof3.42±2.80and3.61±0.20µm,respectively,provingthatthe medicated casein micelles regained its nanostructure after entrapping LOR. Furthermore, they have a polydispersity index of 0.21 and 0.27, respectively, which revealed their homogeneity. Transmission electron microscopeimagesshowedirregularlyroundedorcubicalnon-aggregatedfatglobulesloadedLORwheretheblank oneswerespherical.ThechangeinsurfacemorphologyisattributedtotheincorporationofLORinfatglobules. ThedevelopedHPLC-UVmethodshowedalinearresponseforLORintherangeof0.01-100µg/mLwithahigh correlationcoefficientof0.998,andanexcellentdetectionlimitof0.002µg/mL.Moreover,themeanrecoveries of LOR from whole milk samples ranged from 86.5% to 100.1% using the adopted LLE procedure. The entrapment efficiency for LOR in the milk fat globules was calculated using the developed HPLC-UV and LLE method. It was found to be approximating 100 % whereas, there was no drug detected in the skimmed milk portion.Inconclusion,thefatportionofthemilkcouldbeconsideredasapotentialnanocarrierandextremely stablecolloidaldispersionsystemforthedeliveryoflipophilicdrugssuchasLOR.