The aim of present approach was to design and develop mannose functionalized reverse polymeric nanocomposite(s) system based on release promoter (MRPRPNs). Thus, the composition of the present formulation was optimized by employing the systematic design of experiments (DoE) for screening and optimization using L8-Array Taguchi and 3-level-3-factor Box-Behnken Design (BBD). Further, the developed formulation was observed for its preferential internalization by professional antigen presenting cells (macrophages/dendritic cells) and prompt release of loaded antigen in a pH-dependent manner. The optimized formulation was also extensively characterized for average hydrodynamic diameter, surface potential, poly dispersity index of reverse polymeric nanocomposite(s) which were recoded to be 189.4 ± 8.52 nm, 0.111 ± 0.024, -23.4 ± 2.0 mV, respectively; while percentage entrapment efficiency of OVA in MRPRPNs to be 60.17 ± 2.41%. The release pattern of OVA from MRPRPNs was consistent at pH 7.4. However, at acidic pH (≈5.5) where in protons (H) are in-filtered into the core of MRPRPNs thereby generating the pressure, resultantly causing and creating the pores or disruption of the system thus allowed a prompt release (≈60-70%) of encapsulated OVA from interior to outer milieu within 1 h. MRPRPNs were preferentially internalized through receptor-mediated endocytosis and released the loaded OVA into the cytosol of RAW 264.7 cells. From the above findings, it can be concluded that reverse polymeric system could significantly be loaded with immunobioactive(s) and could potentially deliver the contents at the specific site for the better therapeutic outcome.

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