Hypoxia-based agents (HBAs), such as anaerobic bacteria and bioreductive prodrugs, require both a permeable and hypoxic intratumoural environment to be fully effective. To solve this problem, herein, we report that perfluorocarbon nanoparticles (PNPs) can be used to create a long-lasting, penetrable and hypoxic tumour microenvironment for ensuring both the delivery and activation of subsequently administered HBAs. In addition to the increased permeability and enhanced hypoxia caused by the PNPs, the PNPs can be retained to further achieve the long-term inhibition of intratumoural O
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reperfusion while enhancing HBA accumulation for over 24 h. Therefore, perfluorocarbon materials may have great potential for reigniting clinical research on hypoxia-based drugs.
A prerequisite for successful transdermal or dermal drug therapy is the drug ability to penetration through the skin, especially stratum corneum (SC). The most acceptable technique for measuring skin permeation in vitro is the application of both the Franz diffusion cell device and the skin model. In the skin model, a liposome-based artificial skin membrane (LASM) consisting of tight layers of liposomes immobilized on a filter was prepared and characterized. Using porcine ear skin, rat skin and Strat-M™ artificial membrane as control, the LASM was then evaluated in permeation studies with five active compounds: ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, and tetrahydropalmatine. The scanning electron microscope images demonstrated complete filling of the membrane pores with lipids and the formation of a continuous liposomal coating. The contents of egg phosphatidylcholine (EPC) and cholesterol in LASM were measured to be 12.08 ± 0.18 and 4.41 ± 0.04 mg/cm, respectively. Moreover, revealed by the measurement of electrical resistance, the LASM remains intact for at least 12 h with the incubation of 20% ethanol. The results of permeation studies demonstrated a good correlation (r= 0.9743, r = 0.9871) of P values between the drugs' permeation through LASM and porcine ear skin. In addition, by ATR-FTIR analysis, a slighter shift of CH stretching frequency between LASM and porcine ear skin was observed compared with the shift between Strat-M™ membrane and porcine ear skin. In summary, for the first time, the LASM has been proved to be a valuable alternative to porcine ear skin in permeation studies using Franz diffusion cell device.
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