Nanoparticles derived from plant proteins for controlled release and targeted delivery of therapeutics

Proteins possess several advantages for devel­ opment of nanoscale drug delivery systems, compared with many other natural macro­ molecules and synthetic polymers, in addi­ tion to being biocompatible and biodegrad­ able. Proteins have much more complicated molecular structures, as they are composed of amino acids with side groups differ in length, hydrophobicity, polarity and charge. The molecular complexity results in a vari­ ety of processing approaches to obtain nano­ particulate structures with diverse loading and release capabilities from proteins. Pro­ teins contain both hydrophilic and hydro­ phobic domains composed of self­assembled polypeptide segments with different hydro­ phobicity. The structural amphiphilicity endows proteins capability of loading both hydrophilic and hydrophobic therapeutics. Moreover, with diverse side groups in the composing amino acids, proteins could be readily tuned to carry positive and negative charges, facilitating loading of therapeutics with either positive and negative charges. Due to their unique molecular structures, proteins were used as coating materials for nanoparticles from many other polymers or macromolecules for targeted delivery [1]. Furthermore, functional side groups could be reaction sites for diverse chemical modi­ fications or cross­linking to alter the drug loading and releasing profiles, as well as physiochemical and biological properties of protein nanoparticles. Therefore, protein nanoparticles hold great promise for load­ ing and delivery of insoluble hydrophobic drugs, as well as enzymes, vaccines, growth factors, genes and other large­molecule biopharmaceuticals. Proteins for development of nanoparticles for drug delivery could be obtained from animals and plants. Animal proteins, mostly albumin, gelatin and collagen, are hydro­ philic, leading to low­loading capability of hydrophobic drugs and fast release of pay­ loads due to their instability in aqueous envi­ ronments. Thus, potent cross­linking using toxic chemicals was usually indispensable during formation of animal protein­derived nanoparticles. Furthermore, animal proteins also have potential risks in transmitting dis­ eases, such as bovine spongiform encepha­ lopathy (mad cow diseases) [2]. Recombi­ nant proteins, which are usually generated from recombinant DNAs, are considerably expensive and low in productivity, compar­ ing to the naturally derived animal and plant proteins. With high­loading capacity and potent protection to payloads, nanoparticles from plant proteins have emerged as potential can­ didates for transportation of therapeutics. Compared with animal proteins, plant pro­ teins contain higher contents of hydro phobic amino acids, and thus are usually more hydrophobic and water stable. In general, plant proteins are more stable in aqueous conditions without external cross­linking, have higher loading capacities for hydro­ phobic therapeutics, provide better protec­ tion to payloads and show more sustainable release of payloads. More importantly, using plant proteins could reduce the risk of trans­ mitting zoonotic diseases, which could be a Nanoparticles derived from plant proteins for controlled release and targeted delivery of therapeutics