Development of phospholipid nanoparticles encapsulating 3-O-cetyl ascorbic acid and tocopherol acetate (TA-Cassome) for improving their skin accumulation.

Phospholipid nanoparticles (PNs) encapsulating vitamin C and E derivatives, 3-O-cetyl ascorbic acid (CA) and tocopherol acetate (TA), respectively, were examined using the film rehydration and extrusion method. PN formulations (TA-Cassome) were prepared by mixing CA, soya phosphatidylcholine (Soya PC), sodium cholate, and TA at a molar ratio of 20/80/5/6. Glycerol (GL) or diglycerol (DG) were also added to improve the skin accumulation of CA and TA. Three TA-Cassome formulations were evaluated using a dynamic light scattering (DLS), NMR, TEM, skin accumulation test for CA and TA, and small-angle X-ray diffraction (SAXD) analysis. TA-Cassome formulations (150 nm) were stable for two weeks and they encapsulated 1.8 mg/mL of TA. TEM and SAXD analysis revealed that the nanoparticles formed a spherical multilayer structure. 1H and 31P NMR indicated that GL and DG enhanced the proton mobility of choline groups of soya PC molecules located on the membrane surface of TA-Cassome. Accumulation of CA and TA in the dermis was increased by adding GL and DG. SAXD analysis revealed that GL and DG promoted the formation of new lamellar structures on the stratum corneum, which contributed to improving the skin accumulation of CA and TA.

Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles.

Triple-negative breast cancer (TNBC) is associated with poor survival as chemotherapy is currently limited to conventional cytotoxic agents. Curcumin has promising anticancer actions against TNBC, but its application is hindered by poor bioavailability and rapid degradation in vivo. In the present study, curcumin-loaded phospholipid nanoparticles (Cur-NPs) conjugated with epidermal growth factor (EGF) were prepared for specific targeting of EGF receptors overexpressed in TNBC. NP formulation was performed by reacting EGF peptide with N-hydroxysuccinimide-Polyethylene Glycol-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (NHS-PEG10000-DSPE), followed by efficient curcumin loading through lipid film hydration. EGF conjugation did not significantly affect NP size, zeta potential or morphology. Specific targeting was confirmed by EGF receptor activation and blocking of 125I-labeled NP binding by excess EGF. EGF-Cur-NP dose-dependently suppressed MDA-MB-468 TNBC cell survival (IC50, 620 nM), and completely abolished their capacity to form colonies. The cytotoxic effects were more potent compared with those of free curcumin or Cur-NP. In mice bearing MDA-MB-468 tumors, injections of 10 mg/kg EGF-Cur-NP caused a 59.1% retardation of tumor growth at 3 weeks compared with empty NP, whereas the antitumor effect of Cur-NP was weak. These results indicate that EGF-conjugated NHS-PEG10000-DSPE phospholipid NPs loaded with curcumin may be useful for treating TNBCs that overexpress the EGF receptor.

Characterization and Evaluation of Skin Permeation of Tocopheryl Phosphoric Acid-loaded Phospholipid Nanoparticles.

Tocopheryl phosphoric acid (TPA, a hydrophilic vitamin E derivative) loaded liposome and glycerin containing phospholipid nanoparticles (GPLNP) were prepared using the film rehydration and extrusion method. Nanoparticle formulations were evaluated for size, zeta potential, and in vitro permeation across hairless mouse skin, and 31P NMR spectral analysis was performed. The prepared formulations were stable for 2 weeks, and their mean nanoparticle size varied between 90 and 140 nm. Although glycerin did not affect the particle size of the empty (no TPA) system, TPA-loading resulted in the reduction of particle size and conferred a negative charge. The 31P NMR spectral analysis showed that the presence of glycerin in the formulation changed the nanoparticle structure from a bilayer to a nonbilayer. Moreover, it was suggested that TPA molecules interacted with phospholipid by entrapping nanoparticles in the formulations. TPA did not permeate across the hairless mouse skin after 48 h. However, the TPA concentration in the hairless mouse skin after permeation study increased in the nanoparticle systems and the 30% GPLNP formulation was the best formulation for the accelerated TPA permeation in the hairless mouse skin. These results demonstrate that 30% GPLNP improved TPA permeation in the hairless mouse skin model. And it was strongly suggested that glycerin has an important role for changing the structure of nanoparticles and enhancing the skin permeation of TPA.