Research Of The Mechanism Of Drug Transdermal Enhancement Of Negative Porous PTFE/PE/PP Composite Electret

Porous ploytetrafluoroethylene films prepared in porous PTFE electret by means of unidirectional stretching at a suitably high temperature is widely used as biological electret for its outstanding charge storage stability at high temperature, good ventilation and excellent biological compatibility. The inherent opening porosity structure of porous PTFE composite films have larger interface to air than non-porous PTFE,which drop the charge storage stability of porous PTFE composite films in line with environmental humidity. We prepared the porous PTFE/PE/PP composite electret by heat melting the porous PTFE as charge storage layer, polyethylene (PE) as conglutinated layer and PP as water resistant layer in order to study.1) The charge storage stability and the feasibility in transdermal formulation preparation of porous PTFE/PE/PP were studied as compared with porous PTFE electret by means of isothermal surface potential decay and quasistatic piezoelectricity coefficient d33; 2) In order to prepare a porous PTFE/PE/PP composite electret transdermal formulation, a comparative study of the enhancing effect of negative porous PTFE electret and negative porous PTFE/PE/PP composite electret on drug transdermal delivery, and the exploration of enhancing mechanism of electret on drug transdermal delivery were developed by using fluorescein sodium as model drug and by means of confocol laser scanning microscopy (CLSM). 3) The morphological changes of the skin structure were studied to have a far more understanding of the enhancing effect of electret on drug transdermal delivery by means of scanning electron microscopy and transmission electron microscopy. 4) The enhancing effect of porous PTFE/PE/PP composite electret on transdermal delivery of meloxicam was studied.The results showed that: 1) As compared with porous PTFE electret, negative porous PTFE/PE/PP composite electret not only possessed the same charge storage stability under normal temperature, but also exhibited much better charge storage stability under high humidity circumstance.2) When the model drug of NaFl diffused passively, the fluorescence intensity in stratum corneum increased during the time period of 0.5h～6h, then decreased in the following time period of 6h～14h, and the fluorescence intensity in hair follicle increased during the whole time period. 3)After application of -500V porous PTFE electret on NaFl treated skin, the fluorescent intensity in epidermis increased markedly during the time period of 0.5h～6h and decreased much faster during the time period of 6h～14h as compared with that of control group, but the fluorescent intensities in hair follicles changed almost the same as that of in stratum corneum during the time period of 6h～14h, indicating that the electrostatic field and microcurrent produced by the negative electret loosed epidermis structure, enlarged hair follicles, and enhanced the permeation rate of FINa through skin.4)The -500V porous PTFE/PE/PP composite electret not only showed the same enhancing effect as that of -500V porous PTFE electret, but also showed more remarkable increase than that of -500V porous electret in fluorescent intensities in epidermis. Therefore, due to its better humidity resistance, -500V porous PTFE/PE/PP composite electret could improve the charge storage stability under high humidity, and had better enhancing effect on drug transdermal delivery as compared with -500V porous electret.5)The morphological study of rat skin after electret treatment for 3h indicated disengagement of epidermal cells, increasing of epidermal cranny, alteration of fluid properties of the stratum corneum lipid, desquamation of stratum corneum from epidermis, and looseness of compact structure of stratum corneum, which greatly reduced the barrier function of stratum corneum and help to increase the permeation rate of drug through skin.6) The in vitro permeation study of negative electret transdermal formulation also demonstrated a better enhancing effect on skin penetration of model drug.7) The disruption of regular arrangement of keratinocyte and enlargement of hair follicles caused by negative electret might be the two promotion pathways of the electret on transdermal drug delivery.The results showed that porous PTFE/PE/PP composite electret had excellent charge storage stability and hydropHobicity. The long-term electrostatic field and microcurrent that electret produced could change the arrangement of laminar lipid of stratum corneum and broaden hair follicles which might be the explanation of the enhancing effect of electret on drug transdermal delivery. Therefore, electret can be used as a novel enhancing strategy in transdermal drug delivery system study and will be of great potential drug transdermal formulation preparation in the near future.