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Background: The administration of many pharmaceutical active ingredients is often performed by the injection of an aqueous-based solution. Numerous active ingredients are however, insoluble in water, which complicates their administration and restricts their efficacy. Objective: The current solutions are hindered by both, a time-consuming manufacturing process and unsuitability for hydrophilic and hydrophobic materials. Methods: Emulsions of oleophilic active ingredients and polyprotein microspheres are an important step to overcome insolubility issues. Results: Polyprotein microspheres offer a versatile modifiable morphology, thermal responsivity, and size variation, which allows for the protection and release of assembled biomaterials. In addition, nanospheres present promising cell phagocytosis outcomes in vivo. Conclusion: In this research, a reproducible multifunctional approach, to assemble nanospheres in one step, using a technique termed “automatic nanoscalar interfacial alternation in emulsion” (ANIAE) was developed, incorporating a thermally controlled release mechanism for the assembled target active ingredients. These results demonstrate a viable, universal, multifunctional principal for the pharmaceutical industry.