Both piperine and curcumin have limited clinical applications due to their low water solubility, poor in vitro stability, and low in vivo bioavailability. The research and development of new formulations such as nanoparticles and solid dispersions have solved this problem well. The advantage of the new dosage form is that it increases the solubility and stability of poorly soluble drugs. The possible disadvantages of different preparation methods include time-consuming process, residual solvent, high equipment requirements, and unsuitable for mass production.
1. Polymeric micelles
Polymeric micelles are formed by self-assembly of amphiphilic polymers in aqueous media and have the advantages of good biocompatibility, sustained release performance, and reduced drug uptake by the reticuloendothelial system. The CUR-PIP polymer compound micelles were prepared by the film hydration method. The drug encapsulation efficiency in the micelles was high. The CUR drug loading capacity was 5.63%, the solubility was 1.27 mg/mL, and the encapsulation efficiency was 86.86%; The sealing rate is 77.54%, the particle size of the compound micelle is uniform, the stability of the freeze-dried preparation is increased, and the reconstituted effect is good. The core of the polymer micelle can be loaded with insoluble drugs, thereby improving its solubility and increasing oral bioavailability. The disadvantage is that the requirements for organic solvents are relatively high, and the process is time-consuming.
2. Nanoformulations
Nanoparticles, as good carriers for poorly soluble drugs, can enhance drug stability and solubility and prevent degradation. CUR- and PIP-loaded chitosan nanoparticles were prepared by electrospray method with a particle size of 550 nm, and the encapsulation efficiency of CUR and PIP were 89% and 87%, respectively. The cell survival rate of cystoma is decreased by about 50%, and it has a good tumor cell inhibitory effect. CUR and PIP have synergistic pharmacological activities but different polarities, therefore, core-shell multilayer nanoparticles were prepared using a combination of anti-solvent precipitation and layer-by-layer deposition with CUR encapsulation efficiency and drug loading of 90.4% and 90.4%, respectively. 5.7%, PIP 86.4% and 5.4%, respectively. The compound nanoparticles can slowly release CUR and PIP in a simulated gastrointestinal environment. CUR- and PIP-loaded polymer nanoparticles were prepared by self-assembled nanoprecipitation method, with particle sizes ranging from 80 to 100 nm, with sustained-release properties. Both in vitro and in vivo results confirmed that CUR polymer nanoparticles could inhibit the proliferation of colon cancer cells, and PIP further increased CUR bioavailability, making it more effective against colon cancer. However, the complex preparation process, poor stability, and intragastric degradation are the main reasons for the poor effect of nanotechnology drug delivery systems.
3. Self-microemulsion drug delivery system
The self-microemulsion drug delivery system is composed of a drug, an oil phase, a surfactant, and a co-emulsifier, which can increase the solubility of hydrophobic drugs. Self-microemulsion preparations can spontaneously form oil-in-water microemulsions through the peristalsis of the gastrointestinal tract in the body, which improves the bioavailability of drugs.
4. Solid dispersion
Solid dispersion is the uniform dispersion of drugs in a solid carrier in the form of molecular state, crystallites, amorphous, etc., forming a highly dispersed system, which can increase the solubility and dissolution rate of poorly soluble drugs.
5. Transdermal drug delivery
Few studies have been conducted on the combination of CUR and PIP in transdermal drug delivery systems. The use of PIP as a transdermal enhancer has been reported to increase the transdermal penetration of aceclofenac and repaglinide by approximately 2- to 8-fold.
Both CUR and PIP have a variety of pharmacological effects, such as anti-COVID-19, anti-tumor, lipid-lowering, etc. The two drugs are encapsulated in new dosage forms, which not only increases the solubility and stability of the drug but also improves the pharmacological effect. synergistic effect. The development of dosage forms with clinical application value needs to be continuously explored to overcome the shortcomings faced by different dosage forms. In terms of anti-COVID-19, large-scale randomized controlled clinical trials are needed to confirm its clinical efficacy, and the optimal doses of CUR and PIP as well as the specific mechanisms still require further research.
