Protein-based Nanoparticles Production

CD Bioparticles is a leading manufacturer and supplier of various drug delivery products, including protein-based nanoparticles for R&D and commercialization in a variety of application areas. Among nanoparticles, protein-based nanoparticles have special interests because they are biodegradable, metabolizable, can be easily manipulated and there are various possibilities for surface alteration and/or modification for covalent drug attachment.

Introduction to Protein-based Nanoparticles

In the recent years, natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. Proteins, linear polymers of L-α-amino acids with a wide variety of structures and functions, have unique potential applications in both biomedical and material sciences. As a main advantageous feature, proteins are biocompatible and show biodegradability. By their nature, they offer a multitude of moieties accessible to modifications to tailor drug-binding, imaging or targeting entities. They are considered as ideal materials for nanoparticle preparation because of their amphiphilicity which allows them to interact well with both drugs and solvent. They have been successfully synthesized from various proteins including water-soluble proteins (e.g. bovine and human serum albumin) and insoluble proteins (e.g. zein and gliadin).

Figure 1. Protein-based Nanoparticles drug loading process.

1. Albumin

Albumin is a biocompatible, biodegradable, nonimmunogenic, noninflammatory biomaterial. Pure albumin is freely available as egg white (ovalbumin), bovine serum albumin and human serum albumin (HSA). Since albumin shows high affinity to particular receptors on the cells, they can potentially and specifically be aggregated in the solid tumor cells. The albumin nanocarriers are biodegradable, easy to prepare, and have well-defined sizes and reactive functional groups (thiol, amino, and carboxyl) on their surface that can be used for ligand binding and other surface modifications. Drug release from albumin nanoparticles can be achieved naturally by protease digestion.

2. Gelatin

Gelatin is a natural protein prepared from collagen and is commonly used for pharmaceutical, food, and medical applications, because of its biodegradability and biocompatibility in physiological environments. It is inexpensive, low antigenic, nontoxic and easy to be cross-linked or modified chemically. And it can be sterilized and nonpyrogenic. Gelatin has many ionizable groups such as carboxyl, amino, phenol, and imidazole, which are potential sites for conjugation or chemical modifications. These properties make gelatin-based nanoparticles a promising carrier system for drug delivery.

3. Elastin

Elastin is a protein found in connective tissues. It has the actual property of being elastic. It’s responsible for allowing tissues in the body to “snap back” to their original shape after being stretched or contracted. Elastin is found in artery walls, in the lungs, in the intestines, and of course, in the skin. Elastin is formed through lysine-mediated crosslinking of its soluble precursor tropoelastin. Tropoelastin is a 60–70 kDa protein whose length is dependent on its alternate splicing. Tropoelastin exists as a monomer in solution in two forms: an open globular molecule and a distended polypeptide. The two types of elastin-derived polypeptides that have been used for drug delivery applications are α-elastin and elastin-like polypeptides (ELPs). ELPs are a group of synthetic biopolymers formed from Val-Pro-Gly-Xaa-Gly (VPGXG) pentapeptide in the repeated sequences. Below a certain critical temperature, these materials are water-soluble; while above that temperature, ELPs are folded and form hydrophobic self-assembled structures. They can be used to promote temperature-dependent self-assembly.

4. Gliadin and Legumin

Gliadin is a gluten protein found in wheat that exhibits bioadhesive property and has been explored for oral and topical drug delivery applications. It appears to be suitable polymers for the preparation of nanoparticles which are usually able to interact with biological surfaces such as the gastrointestinal mucosa. Gliadin nanoparticles exhibit a great tropism for upper gastrointestinal regions. Its high capacity to interact with mucosa may be explained by its composition.

Legumin is one of the most important storage proteins in the pea seeds and is the source of sulfur-containing amino acids in these legumes. The solubility of legumin is influenced by pH and ionic strength extremely. The solubility of this protein is reduced during desolvation process, which leads to phase separation and subsequently formation of the nanoparticles. The chemical cross-linking of legumin molecules with glutaraldehyde facilitates their self-assembly to produce nanoparticles.

5. Zein

Zein, the corn prolamin protein, includes a group of alcohol-soluble proteins which are water insoluble. Zein materials, introduced as Generally Recognized As Safe (GRAS) by FDA, are classified in three groups including α-zein, β-zein and γ-zein. Zein nanoparticles are suitable to incorporate hydrophobic bioactive compounds. Nanoparticles from zein proteins have been prepared to encapsulate several drugs and bioactive compounds including ivermectin, coumarin, and 5-FU.

6. Soy Proteins

Soy protein isolates (SPI) are adequate raw materials for the elaboration of nanoparticles. They consist mainly of the components glycinin and β-conglycinin. These proteins are different in terms of molecular weight, constituent amino acids, surface agent and isoelectric point. SPI possesses a balanced composition of polar, nonpolar, and charged amino acids, allowing a variety of drugs to be incorporated. No toxicity was observed from the vitamin B12-loaded SPI nanoparticles on Caco-2 cells and the nanoparticles could easily enter into the cells.

7. Milk Proteins

Milk contains several proteins with unique and diversified functional properties. The use of milk proteins as drug delivery vehicles is a new trend that has received much attention. Casein as the main protein of milk has various benefits such as accessibility, stability, nonantigenicity features. The gel swelling property of casein during changes of pH, encourages its application as a suitable carrier in the field of controlled drug delivery systems. β-lactoglobulin (BLG) is another milk protein which is investigated for drug delivery applications. The ability to preserve its native stable conformation at acidic pH makes BLG resistant to peptic and chymotryptic digestion. Due to its abundance and low cost, BLG is a promising natural polymer for drug delivery applications.

Figure 2. Factors that influence the preparation and performance of protein nanoparticles. (Tarhini, M., et al. International journal of pharmaceutics, 2017, 522(1-2), 172-197.)

Our Protein-based Nanoparticles Featured Services

CD Bioparticles is specialized in the development of drug delivery systems and customizing nanoparticles for drug delivery utilizing our core technologies. With our high-quality products and services, the efficacy of your drug delivery can be tremendously improved.

We offer well-designed protein-based nanoparticles constructed from albumin, gelatin, elastin, gliadin and legumin, zein, soy proteins, and milk proteins. Clients may select the material type, particle size, size distribution, and/or surface functional groups such as carboxyl or amine groups. And we also provide custom services for designing and synthesizing protein-based nanoparticles with special requirement of drug loading, together with its analysis and characterization before and after drug encapsulation.

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References:
1. Lohcharoenkal, W., Wang, L., Chen, Y. C., Rojanasakul, Y. Protein nanoparticles as drug delivery carriers for cancer therapy. BioMed research international, 2014, 2014.
2. Salatin, S., Jelvehgari, M., Maleki-Dizaj, S., Adibkia, K. A sight on protein-based nanoparticles as drug/gene delivery systems. Therapeutic delivery, 2015, (8), 1017-1029.
3. Hernández-Sánchez, et al. Food nanoscience and nanotechnology. Springer, 2015.