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Amino acid and dipeptide prodrugs have been developed to examine their potential in enhancing aqueous solubility and permeability as well as to bypass P-glycoprotein (P-gp) mediated cellular efflux of prednisolone. Prodrugs have been synthesized and identified with LC/MS/MS and NMR. Prodrugs displayed significantly higher aqueous solubility relative to prednisolone. These compounds also exhibited higher stability under acidic conditions relative to basic medium. [14]-Erythromycin uptake remained unaltered in the presence of valine–valine–prednisolone (VVP) indicating lower affinity toward P-gp. Moreover, VVP generated significantly higher transepithelial permeability across MDCK-MDR1 cells compared to prednisolone. Importantly, [3H]-GlySar uptake diminished significantly in the presence of VVP indicating high affinity toward peptide transporters. Moreover, prednisolone was regenerated from VVP due to enzymatic hydrolysis in SIRC cell homogenate. Results obtained from these studies clearly suggest that peptide transporter targeted prodrugs is a viable strategy to improve aqueous solubility and overcome P-gp mediated cellular efflux of prednisolone. [ABSTRACT FROM AUTHOR]

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs. [Display omitted] • Mechanism of protein corona formation • Formation of protein corona affects the fate of nanoparticles in vivo • Using protein corona to facilitate the research of nanodistribution system [ABSTRACT FROM AUTHOR]

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs. [Display omitted] • Mechanism of protein corona formation • Formation of protein corona affects the fate of nanoparticles in vivo • Using protein corona to facilitate the research of nanodistribution system [ABSTRACT FROM AUTHOR]