Currently, biologics and nanoparticle (NP)-based therapies are administered primarily via intravenous or subcutaneous injections. For diseases, which require frequent doses over prolonged periods, such methods of drug administration result in patient incompliance and inconvenience. In these cases, the most preferred way of drug delivery is oral delivery of biologics. Therapeutic biologics are large protein molecules like insulin, calcitonin etc. Their large size, and sensitivity to the complex gastrointestinal environment with of a wide range of pH and enzyme activity, makes it challenging to deliver these biologics orally. Moreover, many transport pathways, like the FcRn pathway, that enable the transcytosis of NPs across the intestinal epithelium to blood, work efficiently for small size NPs. Once the NPs cross the intestinal epithelium, they are susceptible to clearance by the mononuclear phagocyte system. This problem is exacerbated in the case of FcRn-targeted NPs that are decorated with Fc fragments that enhance clearance of the NPs. Rapid release of the payload after transcytosis of NPs into the blood stream is one way of addressing this issue, i.e. the drug is released rapidly before the NPs are cleared. Therefore, the main challenges associated with making NPs which can efficiently deliver large protein molecules across the intestinal epithelium are: (1) to ensure that the NP diameter is small (less than 100 nm), (2) to ensure that the NP has a high protein loading, (3) to make the drug and the NP survive the changes in pH in the complex environment of the gastrointestinal tract, and (4) to trigger quick release of majority of the drug before the NP is excreted from the body. Here, we describe a method to make pH-responsive NPs that address these challenges. To overcome these challenges, we have designed an environment-responsive drug delivery platform comprised of hybrid polymeric NPs which can efficiently encapsulate therapeutic proteins, and yet maintain small NP size Ins-Eud-PLGA-PEG NPs were designed to release insulin when triggered by a change in pH from acidic to neutral. This property of the NPs can be utilized to enable oral delivery of insulin using the FcRn pathway, where the NPs remain intact in the stomach (pH 2-3), upper small intestine (pH 5-6) and in the cellular endosomes (pH 5) where the pH is acidic but on coming in contact with blood (pH 7.4), Eudragit S100 begins to dissolve and the NP loses its integrity, resulting in rapid release of insulin. This drug delivery platform can further be extended to several other biologics which are currently being administered intravenously or subcutaneously. Successful implantation of this technique can significantly improve the quality of life of millions of patients across the globe.