Can nanoparticles and nano-protein interactions bring a bright future for insulin delivery?

Insulin therapy plays an essential role in the treatment of diabetes mellitus.However,frequent injections required to effectively control the glycemic levels lead to substantial inconvenience and low patient compliance.In order to improve insulin delivery,many efforts have been made,such as developing the nanoparticles (NPs)-based release systems and oral insulin.Although some improvements have been achieved,the ultimate results are still unsatisfying and none of insulin-loaded NPs systems have been approved for clinical use so far.Recently,nano?protein interactions and protein corona formation have drawn much attention due to their negative influence on the in vivo fate of NPs systems.As the other side of a coin,such interactions can also be used for constructing advanced drug delivery systems.Herein,we aim to provide an insight into the advance and flaws of various NPs-based insulin delivery systems.Particularly,an interesting discussion on nano?protein interactions and its potentials for developing novel insulin delivery systems is initiated.

The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery

Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes.Previously,we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse,which is among the most efficient methods to date.However,plasmid DNAs(pDNAs)in this method were not compressed,making them unstable and inefficient in vivo.We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system.Here,we reported our finding of such a material,Epigallocatechin gallate(EGCG),a natural compound in green teas,which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system.Meanwhile,we found that polyethylenimine(PEI)could also slightly improve exogenous gene expression in the optimal procedure.By analysing the characteristic differences between EGCG and PEI,we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery,such as EGCG,are better alternatives than cationic materials(like PEI)for muscle-based gene delivery.The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged.This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.