NOVEL DOUBLE LOADED TRANSFEROSOMES: EVIDENCE OF SUPERIOR ANTI- INFLAMMATORY EFFICACY- A COMPARATIVE STUDY

The main aim of this study was to enhance the transdermal penetration of a poorly water-soluble NSAID, Piroxicam, by encapsulating it into a nanocarrier namely transferosomes. In order to increase the drug encapsulation into the transferosomes, water soluble cyclodextrin complex solutions of drug were entrapped into the aqueous phase of stable unilamellar transferosomes in addition to incorporating into the liposomal bilayer by the thin film hydration method and sonication. TEM measurements suggested that, the drug cyclodextrin complexes we re successfully loaded into the transferosomes without affecting their morphology. At optimal conditions, the mean particle size of double loaded transferosomes was ~158.7 nm and entrapment efficiency of ~85.7% was achieved. Addition of surfactant provides adequate fluidity to the bilayer which was further confirmed by DSC and FTIR of skin. The entrapment efficiency was increased when compared with the batches not containing the cyclodextrin complexes. The optimized formulation shows no interaction with skin components which was confirmed by skin-vesicles interaction and ex-vivo corrosion studies. Transferosomes containing cyclodextrin inclusion complexes released more drug than transferosomes encapsulating non-complexed drug, the drug release being related to entrapment efficiency. Ex-vivo lipid peroxidation studies revealed that double loaded Piroxicam transferosomes showed two times effectiveness in preventing free radical damage when compared with non-complexed drug loaded transferosomes, while it showed almost four times effectiveness against the solution of non-complexed drug in distilled water. The formulation also demonstrated superior anti inflammatory activity in rodents compared through in-vivo carrageenan induced rat paw edema model. INTRODUTION Conventional pharmaceutical dosage forms which are widely administered dermally are gels, creams and ointments. Transdermal use of carbopol gels is beneficial as they possess good rheological properties resulting in long retention time at the site of administration and high drug concentration on skin. Different approaches have been performed to enhance the transdermal passage of drugs to overcome the low skin permeability. Topical delivery of drugs formulated in lipid vesicle forms attracts considerable attention. Liposomal formulations are widely used in the pharmaceutical field as drug delivery systems due to their flexibility and clinical efficacy. Topical liposome formulations act as a solubilizing matrix for poorly water soluble drugs, as penetration enhancer and simultaneously a local depot which can be more effective and less toxic in comparison with conventional formulations. The liposomal gel formulations can perform better therapeutic effects than the conventional formulations, whereas their prolonged and controlled release property may lead to improved efficiency and better patient compliance. However, in most cases it has been shown that conventional liposomes, because of high drug deposition in the upper layers of the skin and low penetration into the deeper layers, have low efficiency as a carrier in transdermal drug delivery. Hence a new class of liposomes also called as Transferosomes® have been developed. Transferosomes are promising nanocarriers for non invasive transdermal delivery. Better drug delivery by transferosomes is due to the driving force provided by the osmotic gradient between outer and inner layer of stratum corneum [1], thus, they can pass through the intact skin spontaneously under the influence of the naturally occurring in vivo transcutaneous hydration gradient. These nanocarriers possesses an edge activator(EA) such as sodium deoxycholate, span 80 or tween 80 which provides stress dependant adaptability to these carriers so that they can easily squeeze between the pores of the stratum corneum. Also, transferosomes are colloidal carriers which are easily accumulated into the leaky synovial tissue which leads to peripheral targeting. Transferosomes also act as depot resulting in controlled drug delivery system.