Transdermal Drug Delivery Of Chitosan-Coated Lidocaine Hydrochloride Liposome

Objective:Transdermal drug delivery systems (TDDS) has made important contributions to medical practices and has several advantages including eliminating first-pass hepatic metabolism, providing release of drug for sustained time, avoiding painful and improving patient compliance. TDDS have so many advantage such as easy to operation, painless, no damage, no pain and reduce the phobia of patients used for local anesthesia, especially suitable to some local anesthesia unfavorable for local infiltrating anesthesia and some local anesthesia which need a long analgesia time. TDDS as drug carrier local anesthesia has wide prospect of clinical application.Local anesthetic agents (LID) as analgesic with strong fast effect-acting and mucous membrane penetration, can eliminate pain in a circumscribed area of the body and minimize patients'phobia. It is a kind of ideal local anesthetic. However, the main pharmaceutics of LID is injection and gel in clinic, injection is inconvenience and can bring pain and psychological fear to patients, and gel only used for mucous membrane, both of them are all can not meet the requirement of local anesthetic for skin.In this research, LID as model drug, we used CH modified transfersome and noisome, In order to avail a new a new pharmaceutics for skin small surgery application which painless, no damage, convenient, reduce pain and psychological fear to patients, we used CH to modify transfersome and niosome. These new pharmaceutics we obtained can penetrate skin and reach the dermis superficial in a short time and can delay release the drug. As painkillers for small surgery, the data of CH coated transfersome (CCT) and CH coated noisome (CCN) can provide a basis theoretical for clinic. Method:In this study, an effective transdermal delivery system for local anaesthetic was developed with lidocaine hydrochloride (LI D) as model drug. Transfersome composed of soya lecithin with sur factant as edge activator, was prepared by rotary evaporation sonicat ion method. We studied the influence of surfactant, drug and CH to the size, Zeta potential and encapsulation efficiency of CCT and d etermined the prescription composition.LID as model drug, niosome composed of non-ionic surfactant was prepared by rotary evaporation sonication method. We studied the influence of non-ionic surfactant, drug, cholesterol and CH to the size, Zeta potential and encapsulation efficiency of CCT and determined the prescription composition.The morphology, vesicles size, polydispersity index (PI) and zeta potential of CCT and CCN were analyzed by TEM and dynamic light scattering (DLS). The deformation and stability at the room temperature and4℃of CCT and CCN also be studied.In vitro release and In vitro permeation study of LID from different vesicular formulations were determined using a Franz diffusion cells with cellulose membrane and the skin of the rats. The flux and drug deposition of CCT and CCN were studied. The painkiller effect of CCT and CCN were studied by formalin pain model and the security of CCT and CCN were test on rabbits.Result:The factor analysis results show that add the surface the Zeta potential reduce and it is no effect to the vesicles size. When the content of SDC surface was15%(w/w), we get the highest EE%. Chitosan (CH)(0.1-0.5%, w/v) coated transfersome by electrostatic attraction of negative transfersome and positive CH. CH coating changed the transfersome surface charge and increased the vesicle size. EE% decreased with the increase of CH content. Results show that the CH content is0.3%(w/v), SDC content is15%(w/w), the ratio of lipid and drugs is3:1, phospholipids and cholesterol ratio is1:1are the best prescription of CCT.The factor analysis results show that ethanol can reduce the noisome size and increase the EE%. The encapsulation rate of noisome which prepared with Span20, Span60, Tween20and Tween60were49.7%,65.2%,51.5%and78.9%. The EE%of niosome increasing with the content of cholesterol, the highest EE%was on the ratio of lipid and cholesterol at1:1. Chitosan (CH)(0.1-0.5%, w/v) coated niosome by electrostatic attraction of negative transfersome and positive CH. CH coating changed the niosome surface charge and increased the vesicle size. EE%decreased with the increase of CH content. Results show that the CH content is0.3%(w/v), LID content is0.5mg/ml, the ratio of lipid and drugs is3:1, ethanol content is20%are the best prescription of CCN.The morphology, vesicles size, polydispersity index (PI) and zeta potential were analyzed by TEM and dynamic light scattering (DLS). Results show that CCT and CCN are all homogenous spherical in shape and there is a shell after coated by CH. After coated, the deformation of transfersome and noisome reduce. CH coated elastic vesicles demonstrated an improved physicochemical stability at4℃in a3month storage period. CCT and CCN displayed a prolonged drug release profile in vitro release study. The in vitro permeation study showed that CCT and CCN were able to give a statistically significant improvement of skin permeation of LID in comparison with elastic vesicle (transfersome and niosome) and CH solution. CCT and CCN significantly reduced pain compared with elastic vesicles (transfersome and niosome) and CH solution. Conclusion The research had successfully prepared CCT and CCN which have excellent painkiller effective. These pharmaceutics safe, non-toxic, can penetrate the skin reach the dermis. CCT and CCN might be a potential TDDS for local anaesthetic.