Preparation and research progress of drug-loaded albumin nanoparticles

Albumin, also known as serum protein, has a wide range of sources.
The common ones are ovalbumin, bovine serum albumin, human serum albumin and genetically recombinant human serum albumin
.
Serum albumin is the most abundant protein in plasma.

In January 2005, the US FDA approved Paclitaxel for injection (albumin-bound type, trade name Abraxane) developed by American BioScience, which became the world's first successful case of albumin nanoparticle drug delivery system.
There are many applications of this product on the market.
Poorly soluble drugs and poorly targeted drug preparations provide new ideas and new methods.
In addition, albumin nano preparations such as docetaxel, rapamycin, and allylaminogeldanamycin have also entered the clinical research stage
.

Preparation process of albumin nanoparticles

Common preparation methods of albumin nanoparticles mainly include desolvation method, emulsification and solidification method, self-assembly technology, Nab ^TM technology and pH-aggregation method
.

Desolvation

The desolvation method is a commonly used method for preparing albumin nanoparticles.
The hydration film of albumin is removed by dehydrating agent (ethanol, acetone, etc.
), so that albumin is precipitated due to the exposure of its hydrophobic area, and then it is denatured by heat or added The chemical cross-linking agent (such as glutaraldehyde) denatures the albumin to form stable albumin nanoparticles.
Finally, the residual cross-linking agent and organic solvent are purified and removed, so that purified albumin nanoparticles are obtained
.
The desolvation method can prepare albumin nanoparticles with a diameter of 200~500nm, and is mostly suitable for the preparation of hydrophobic drug albumin carriers.

Emulsion curing method

The emulsification and solidification method is mainly suitable for the preparation of nanoparticles loaded with hydrophobic drugs.
The albumin aqueous solution and the aqueous drug solution are added to organic solvents such as vegetable oil or isooctane containing an appropriate amount of emulsifier, and the mixture is stirred, ultrasonic or high-pressure homogenization.
Emulsify to obtain a water-in-oil (W/O) emulsion
.
Then, the liquid droplets are solidified by thermal denaturation or chemical cross-linking, and the contained organic phase is removed, and finally albumin nanoparticles are obtained

Self-assembly technology

Self-assembly technology is to increase the hydrophobicity of albumin molecules through certain methods, such as reduction of disulfide bonds in protein molecules, adding denaturants, adding lipophilic drugs, or reducing primary amine groups on the protein surface
.
After the hydrophobicity of albumin is increased, drug molecules can bind to the hydrophobic region of albumin, thereby inducing the formation of albumin nanoparticles

Nab ^TM technology

       Nab ^TM technology was developed and developed by American Bioscience.
At the same time, based on Nab ^TM technology , the company successfully developed paclitaxel albumin nanoparticles (Abraxane) that has been approved for marketing by the FDA
.
This technology is to dissolve hydrophobic drugs in a non-polar solvent, and then add them to a solution with albumin as the water phase and as a matrix and stabilizer under high shear force (ultrasonic treatment, high pressure homogenization, etc.

       pH-coagulation method

       By changing the pH value of the system, the protein can be precipitated to generate nanoparticles
.
However, only by changing the pH value of the system to prepare nanoparticles, it is not convenient to control the particle size of the nanoparticles

       Application of Albumin Nano Drug Delivery System

       The albumin nano-drug carrier system uses albumin as a carrier to encapsulate or adsorb drugs, and form solid spheres after solidification and separation.
It is a solid colloidal drug release system that has high targeting, controlled drug release, and improves the solubility of poorly soluble drugs.
The advantages of absorption rate can improve the efficacy of drugs and reduce toxic and side effects
.
Therefore, in recent years, albumin nano-drug delivery system has become a research hotspot in targeted tumor therapy

       Drug-loaded albumin nanoparticles: There are many drug binding sites on the albumin molecule, which can better bind a variety of drugs; in addition, albumin can be used as a source of energy and amino acids for tumors and inflammatory tissues to be enriched in these sites
.
The use of albumin to prepare nanoparticles can not only better load drugs, improve drug properties, but also increase the accumulation of drugs in tumor sites, which is a better strategy

       Modified albumin nanoparticles: Although the retention effect of nanoparticles and gp60-mediated active targeting can enhance the accumulation of drugs in tumors, there are still some albumin nanoparticles that have insufficient targeting and tissue penetration cannot reach deep tumors.
And so on
.
Modifying tumor cell-specific ligands on the surface of nanoparticles can further improve the ability of nanoparticles to target tumor cells, and improve the pharmacokinetics and tissue distribution properties of the nanoparticles
.
Studies have selected human ovarian cancer SKOV3 cells as model cells and used folate-coupled albumin nanoparticles to explore the tumor cell targeting of cancer cells in vitro, and confirmed that folate-coupled albumin nanoparticles can be mediated by folate receptors on the cell membrane.
Pathway, actively targeting tumor cells rich in folate receptors
.

       Microenvironment-sensitive albumin nanoparticles: In addition to designing targeted nanoparticles, it is also possible to design condition-sensitive nanoparticles based on the characteristics of the tumor microenvironment by modifying albumin to achieve controlled release of drugs, so that the nanoparticles can only be used in tumors.
The site releases the drug and is stable under physiological conditions, thereby reducing the toxic and side effects of the drug
.
Some studies use tamoxifen (TAM) as a hydrophobic part to promote the self-assembly of HSA-Ce6 to form nanoparticles.
A sensitive albumin nanoparticle that disintegrates at low pH has been designed.
Good stability, its large particle size (about 130nm) realizes the accumulation of nanoparticles in the tumor site through the retention effect
.
Then the acidic environment of the tumor site leads to protonation of TAM, which transforms TAM from hydrophobic to hydrophilic, which further causes the disintegration of nanoparticles into smaller particle sizes (about 10nm), thereby enhancing the tissue penetration ability of the drug
.

       Albumin is the main protein in blood circulation.
There are a variety of drug binding sites and modifiable functional groups on the surface, which can better bind drugs and functional modifications; albumin can also be used as a passive target of energy and amino acid sources for tumor tissues In addition, albumin also has the characteristics of good biocompatibility, non-immunogenicity, and biodegradability.
Therefore, albumin is an ideal new drug carrier, and its application prospects are very broad
.
Currently albumin as a carrier of anticancer drugs is a hot research, clinical application of albumin nanoparticles are increasing, such as Abraxane is the first FDA-approved based on albumin preparation of chemotherapy drugs for the treatment of breast cancer, and the other with Abraxane The combined application of other chemotherapeutic drugs is also constantly being explored
.
With the continuous deepening of research on nano-delivery systems, albumin nanoparticles will play a huge role in anti-tumor and other treatments
.

       references:

       [1] Tao Linlin, Huo Meirong, Xu Wei.
Research progress of protein nanocarrier materials[J].
Journal of China Pharmaceutical University, 2020, 51(02): 121-129.

       [2] Li Hui, Wang Dandan, Yang Han, Zhang Xuenong.
Research progress of drug-loaded albumin nanoparticles[J].
Chinese Pharmacovigilance, 2020, 17(09): 636-642.

       [3]Wang Xiaowei, Liu Rui, Zhang Hongyan, Wang Dongkai.
Research progress of albumin as a carrier of anti-tumor drug delivery system[J].
Chinese Journal of Pharmacy, 2020, 18(05): 250-261.
       

       About the author: Shaluo, a drug research and development worker, currently works in a large domestic drug research and development company, dedicated to the research and development of new Chinese medicines
.