l -Ascorbic acid (LAA) is considered a powerful antioxidant that protects skin from premature aging. Maintaining the stability of vitamin C remains the biggest challenge in cosmeceuticals. Our main aim is the entrapment of high dose of vitamin C in spanlastic vesicles to provide maximum stability and efficacy. LAA-loaded spanlastics were prepared by ethanol injection method and were characterized for entrapment efficiency (EE%), particles size (PS), polydispersity index (PDI), zeta potential, deformability index (DI) and in vivo skin permeation. Selected spanlastics formula composed of span 60 and tween 60 (5:1) showed highest EE% of 89.77 ± 3.61% (w/w), high deformability of 11.13 ± 1.145 as well as good physical and chemical stability for 6 months. Improved drug penetration into stratum corneum (SC) was obtained from spanlastics compared to topical LAA solution. Quantitative real time PCR revealed that MMP2 and MMP9 levels were significantly suppressed in response to LAA spanlastics treated rats by 30.4% and 65.3%, respectively, when compared to the control group after exposure to UV irradiation. Results were confirmed by western blot analysis. Histopathological study of rat skin after UV irradiation revealed that application of LAA-loaded spanlastics provided the highest skin protection compared to UVB and LAA solution treated group which was evident by the normal thick epidermal morphology and the densely arranged dermal collagen fibers. LAA-loaded spanlastics successfully improved LAA stability, skin permeation and antioxidant protection against skin photodamage.

Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatment. Amalgamation of different treatment modalities is expected to provide better cancer combating. Herein, We developed a long circulating nanocarrier comprising trastuzumab (TZB) surface modified polylactic-co-glycolic acid (pLGA) nanoparticles (nps) co-encapsulating magnolol (Mag) and gold nanoparticles (GNPs). A modified single step nanoprecipitation method was adopted ensuring particle coating with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) while co-encapsulating Gnps. tZB was then anchored on nps surface using a carbodiimide chemistry. the cytotoxicity of the developed system was evaluated with and without photothermal irradiation. nps cellular uptake was then followed using confocal microscopical imaging. A hybrid matrix composed of pLGA/tpGS and surface decorated with TZB with a conjugation efficiency of ˃65%, was confirmed via ftiR, 1 HnMR. Gnps could only be included in the nps, when placed in the organic phase as evidenced by the shifted GNPs surface plasmonic resonance and confirmed via imaging coupled with energy dispersive X-ray analysis. Optimized NPs (136.1 ± 1.3 nm, −8.2 ± 1 mV and Mag encapsulation efficiency of 81.4 ± 1.8%) were able to boost Mag cytotoxicity on breast cancer cells while providing a selective multifunctional therapy with an added photothermal effect. Despite the great advances in cancer research, breast cancer remains one of the most challenging diseases risking the lives of a considerable proportion of women world wide 1. Lack of selectivity, poor drug penetration in solid tumors, multi drug resistance (MDR) with increased cells sensitivity added to the drug systemic side effects, represent some of the major barriers for a successful therapy 2. Smart drug delivery systems incorporating different cancer targeting approaches including: passive, active and stimuli responsive had been suggested to improve outcomes of cancer treatment 3,4. In this study, we focused on integrating many strategies that could potentiate the effect of a natural cytotoxic drug with potential activity against breast cancer. Magnolol (Mag), see structure Fig. S1, is a phenolic polyhydroxy compound isolated from the root and stem bark of Magnolia Officinalis 5. It had been found to inhibit proliferation and induce apoptosis in MCF-7 breast cancer cells via the intrinsic pathway with release of apoptosis inducing factor from mitochondria 5,6. Studies have also shown that Mag inhibited cell growth and HER2-mediated tumor metastasis in human HER2-cancer cells 7. Although, Mag might be considered a potential lead drug in breast cancer treatment yet, its delivery is usually hampered by poor aqueous solubility and low oral bioavailability 6,8. Hence, its incorporation in a smart nanocarrier is expected to improve its delivery characteristics and boost its anticancer properties especially with the incorporation of multifunctional adjuvants.

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