Combination Of Light Needles And ZnPC₄-Loaded Cubic Phases For Regional Treatment Of Basal Cell Cancer

Objective: Combination of fractional ablative carbon-dioxide laser?light needles?and local photodynamic therapy?PDT?was explored for regional treatment of basal cell cancer?BCC?with high efficiency and safety.The mechanism was studied in vitro and in vivo.Methods:?-Tetra-?4-carboxyl-phenoxy?-zinc phthalocyanine?ZnPC₄?-loaded cubic phases were synthesized and prepared with the optimal formulation and preparation technology.The types and energy of light needles and animal species were evaluated based on hole depth,width and healing recovery of ablated skin by light needles.The influence of light needles energy on human epidermal cancer cells A-431 was investigated.The toxic effects of laser parameters,including laser power,laser irradiation time,and dark incubation time,were evaluated on A-431.Nude mice with BCC was established for pharmacodynamics.The combination effect of light needles with low energy?53 mJ/cm2?and photosensitizer-loaded cubic phase on BCC treatment was evaluated.The direct extinction effect of light needles with high energy?238 mJ/cm2?,and combination effect on BCC treatment of light needles with high energy and photosensitizer-loaded cubic phase were also evaluated.Living body imaging of small animals were used to monitor the distribution of ZnPC₄ cubic phases in vivo under the action of light needles with different energy.The influence of ZnPC₄ on the apoptosis of A-431 cells was detected by flow cytometry.Irritation of ZnPC₄ cubic phase on rabbit skin was also studied.Results: ZnPC₄-loaded cubic phases with high drug loading and good spreading ability were prepared with glyceryl monooleate?GMO?as the major excipient.Pores of different depth and width fromed on skin under the action of lightneedles.With the energy of light needles increased,the hole depth and width also increased.After light needles application,the nude mice recovered the fastest,and the next was SD rat and guinea pig.With energy of light needles increased,the survival rate of A-431 cells decreased gradually.The optimized laser parameters for the best treatment effect of ZnPC₄ cubic phases were as the followings,irradiation power of 150 mW,irradiation time of 5 min,dark incubation time of 4 h.IC50 of ZnPC₄ cubic phases under the laser irridation with the same conditions mentioned above was 20 ?g/mL.Light needles of low energy could promote transdermal absorption of ZnP C4-loaded cubic phases.Light needles of high energy together with ZnPC₄-loaded cubic phases could completely kill tumor cells with no recurrence.ZnPC₄-loaded cubic phases alone could not completely inhibit tumor growth.Conclusion: The advantages of ZnPC₄-loaded cubic phases included easy preparation and use,long local retention and little toxicity.Combined use of light needles and ZnPC₄-loaded cubic phases can effectively treat BCC with no recurrence.It is promising in clinical treatment of BCC.