New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. The use of solvents that affect the skin barrier function is one of the classic strategies of penetration enhancement. The liposomes as a delivery system for hydrophobic and hydrophilic drugs is well recognized Standardized poly(ethylene glycol)modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies. The aim of present work was to investigate the potential utility of novel carrier gel core liposomes. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. The study includes the development of liposomal and ethosomal gels for transdermal delivery to overcome the side effects associated with oral route and comparing the latest gel-core liposomes (hyaluosomes) with non-conventional liposomal systems such as propylene glycol (PG)-liposomes, ethosomes, transferosomes and conventional liposomes. With the advancement in liposomal sciences, it warrants that hyaluosomes as a promising transdermal liposomal system for favourable rheological characteristics as well as superior transdermal permeation that proved greater capacity than conventional and other non-conventional liposomal systems.