Abstract
•Buffalo's milk was investigated as a natural lipophilic carrier for delivery of a model lipophilic drug, lornoxicam.•Particle size, surface morphology, and entrapment efficiency of lornoxicam into fat globules was investigated.•A new HPLC-UV method coupled with LEE was developed for determination of entrapment efficiency.•High sensitivity down to 2 ppb was reached allowing accurate assay of lornoxicam in milk as a formulation or excretion route.
Searching for safe and effective drug delivery carriers has gained a lot of demand in recent years. This is why natural carriers become the target of researchers working in that field. In this study, buffalo's milk is investigated as a natural lipophilic carrier for the delivery of a model lipophilic drug, lornoxicam (LOR). LOR has been loaded into milk fat globules via homogenization. The homogenized fat globules and casein micelles were characterized for their size, charge, surface morphology, and entrapment efficiency of LOR into fat globules. A new HPLC-UV detection method coupled with liquid-liquid extraction (LLE) procedure was developed and fully validated for the quantitative determination of LOR in fat globules. Results showed that dynamic light scattering of blank and loaded fat globules had a similar particle sizes of 3.42±2.80 and 3.61±0.20 µm, respectively, proving that the 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 microscope images showed irregularly rounded or cubical non-aggregated fat globules loaded LOR where the blank ones were spherical. The change in surface morphology is attributed to the incorporation of LOR in fat globules. The developed HPLC-UV method showed a linear response for LOR in the range of 0.01-100 µg/mL with a high correlation coefficient of 0.998, and an excellent detection limit of 0.002 µg/mL. Moreover, the mean recoveries 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. In conclusion, the fat portion of the milk could be considered as a potential nanocarrier and extremely stable colloidal dispersion system for the delivery of lipophilic drugs such as LOR.