In the last decades, the pharmaceutic industry has shown great interest in new products for drug delivery, since the studies with drug nanocarriers evidenced the application potential of these systems. A relatively new strategy for nano drug deliver is the use of cubosomes, which is a nanoparticle with crystalline structure formed by lipid bilayer created for instance with monoolein lipid and Pluronic F127 as a stabilizer. The internal crystalline structure with hydrophobic region in the acyl region of lipid bilayers plus hydrophilic region provided in the water labyrinths, provides relatively high surface area for encapsulation of diverse drugs and bioactives. In our studies we develop a cubosomes containing biopolymers-shell for the delivery of acemannan as a bioactive extracted from aloe vera, which has immunomodulation properties. The cubosome was produced using 45mM of monoolein and Pluronic F127 at 7% w/w, adding aqueous solutions of chitosan-N-arginine, alginate and acemannan. The mixture was subjected to 10 times mixing (1min) and bath sonication (5min) following our previously described protocols. The samples were studied by means of dynamic light scattering, zeta potential and isothermal titration calorimetry to evaluate the thermodynamic interaction of the hybrid cubosomes with liposomes produced with POPG, as a model cell membrane, in different pH conditions. The encapsulation percentage and delivery profiles of acemannan were besides accessed through spectrophotometry techniques. The encapsulation of acemannan was highly effective and delivery was attenuated and sustained, further suggesting the potential of the hybrid cubosome as a bioactive delivery system. The interaction of the hybrid cubosome with liposomes, evidenced by thermodynamic results, was favored in two different pHs (2.5 and 7.4). The hybrid cubosomes present different physicochemical characteristics depending on pH, which play a role in the enthalpic and entropic contributions during the interaction. Overall, the results indicate potential of the hybrid cubosomes for oral administration of acemannan.