In the present report polyelectrolytes stabilized liposomes (layersomes) were hypothesized and assumed to protect the insulin entrapped within the layersomes. furthermore layersomes were functionalized by using folic acid (fa) as targeting ligand and were hypothesized to follow additional receptor mediated endocytosis uptake mechanism for enhanced bioavailability. to make the liposomes stable alternating coating of oppositely charged polyelectrolytes was applied over the liposome core which resulted into the formation of robust structure “layersomes”. liposomes were made positively charged by taking stearyl amine as formulation component. these positively charged liposomes were taken as the template for subsequent coatings with negatively charged poly acrylic acid (paa) and then with positively charged poly allyl amine hydrochloride (pah) in layer by layer manner. fa functionalization was done by synthesizing fa-peg-pah conjugate and its use in place of simple pah during second step of coating. different preparative variables at every step were extensively optimized which resulted in the formation of fa-ins-layersomes with optimum critical quality attributes. following the development, surface morphology was examined by using sem, tem and afm, which revealed the formation of almost spherical particles. in order to convert the fa-ins-layersomes into lyophilized form, freeze drying was accomplished following our previously patented freeze drying cycle. in vitro release profile was examined in three different media i.e simulated gastric fluid (sgf, ph 1.2), simulated intestinal fluid (sif, ph 6.8) and pbs (ph 7.4) in order to mimic the bio-environmental conditions followed by a formulation during its entire journey following oral administration. almost similar release profile was observed in all the fluids irrespective of the ph of the medium. chemical stability of the insulin, entrapped within the freeze dried fa-ins-layersomes was confirmed by rp-hplc method and native-page. conformational stability was evidenced by the overlay spectra of cd spectroscopy. beside the stability of the entrapped insulin, stability of the developed formulation in simulated biological fluids is also equally important to have the desired therapeutic performance. the developed fa-ins-layersomes demonstrated excellent stability in simulated biological fluids and could be attributed to the formation of robust structure due to the strong electrostatic interaction. storage stability testing according to ich guidelines revealed that the fa-ins-layersomes were stable at 2-25°c and humidity up to 60±5% for 6 months without compromising with the quality attributes of the product indicating the suitability of designed systems for the delivery of delicate drugs like insulin. caco-2 cells and ex vivo intestinal uptake studies were designed for mechanistic understanding of the uptake mechanism. remarkably higher uptake was observed in case of fa functionalized formulations. fa functionalization demonstrated 3.33 folds higher uptake of fa-ins-layersomes in comparison with liposomes. ex vivo intestinal uptake studies further confirmed remarkably higher uptake of fa functionalized layersomes in comparison to their plain counterparts. for efficacy testing sprague-dawley rats were used and the diabetes was induced by intraperitoneal administration of stz at a single dose of 55 mg/kg. diabetic animals were randomly distributed into different treatment groups and kept on overnight fasting prior to initiation of study and treated by standard insulin solution sc at a dose of 5 iu/kg and orally at a dose equivalent of 50 iu/kg. subcutaneous insulin exhibited severe transient hypoglycemia while oral insulin solution was practically inactive as no blood glucose reduction was observed. fa-ins-layersomes revealed almost double (1.92 folds) cumulative hypoglycemia in comparison with subcutaneously administered standard insulin solution, cmax (34.1±2.2 μiu/ml) within 6 h and the highest bar (19.3±1.6) among all the treatment groups. overall the proposed strategies are expected to contribute significantly in the field of designing ligand anchored stable lipidic and polymeric systems in drug delivery.