Oral Nano-drug Delivery System 2
The previous article introduced the relevant information about choosing liposomes and nanoparticles as drug carriers in oral nano-drug delivery systems. This article will continue to introduce the feature of microemulsions, polymers, dendrimers and nano-drug crystals as oral drug carriers.
Microemulsion
Microemulsion is formed by mixing water phase, oil phase, surfactant and co-surfactant in appropriate proportions, with a particle size of 10~100mpm, transparent or translucent, low viscosity, isotropic thermodynamics and kinetics For a stable oil-water mixing system, there is also literature that the particle size of the microemulsion is 20~200nm.
Microemulsions have received extensive attention in recent years because of their significant targeting, sustained-release effects and strong solubilization effects on poorly soluble drugs. After oral administration, microemulsion can be absorbed through the lymph, can avoid the first pass effect of the liver, and can overcome the obstacle of macromolecular drugs passing through the gastrointestinal epithelial cell membrane. The surface tension of the microemulsion is low, and it is easy to pass through the hydration layer of the gastrointestinal tract, so that the drug directly contacts with the epithelial cells of the gastrointestinal tract to promote absorption and improve bioavailability. At present, the microemulsion preparations that have been marketed for clinical use include cyclosporin A self-microemulsifying preparation capsules, clotrimazole microemulsion, carboxymethyl gluconate D-panthenol and copper pyridine sulfate microemulsion for treating psoriasis and neurodermatitis.
Polymer Micelles
The polymer micelles are composed of amphiphilic polymers. When the concentration of amphiphilic polymers in water exceeds the critical micelle concentration (CMC), the molecules spontaneously form thermodynamically stable micelles with lipophilic core and hydrophilic shell structures. The particle size of polymer micelles is in the range of 10~100nm, and the particle size distribution is generally narrow. Polymer micelles are similar to surfactant micelles, except that the polymer CMC is several orders of magnitude lower than that of surfactants. Therefore, polymer micelles are more resistant to body fluid dilution and more stable than small molecule micelles. The hydrophobic core of the polymer micelle can be used as a reservoir for poorly soluble drugs, and the hydrophilic shell can contain water-soluble drugs. The structure, surface properties (such as biotin, polypeptide modification), size, and surface potential of micelles will affect their in vivo behavior, further achieving controlled drug release and targeting. The small particle size of the orally administered polymer micelles facilitates crossing the mucosal barrier, increases the stability of the encapsulated drugs, promotes drug absorption, and improves drug bioavailability.
Dendrimer
Dendrimers, also known as dendrimers, are new synthetic polymer nanomaterials. They were first invented and successfully synthesized by American chemist Dr. Tomaia in the 1980s. A dendrimer is a monodisperse macromolecule with a repeating unit structure and a high degree of branching. Dendrimers can be regarded as single-molecule micelles, which overcome the shortcomings of traditional micelle molecules that need to reach CMC. Small molecular compounds can be wrapped inside to achieve controlled release under certain conditions. There are a large number of reactive groups on the surface of dendrimer. Drug molecules can be physically embedded in it, or chemically bonded to the surface; at the same time, other types of dendrimers can be attached to the surface or nano-encapsulated inside. Gold to optimize its performance. After the drug is coupled with the dendrimer, it can increase the stability, shield the antigen point of action, reduce glomerular filtration, prolong the circulation time in the body, reduce the administration dose, and achieve controlled drug release and passive targeting. The dendrimer surface can also be modified by antibodies and ligands to achieve high targeting. Dendrimers have been widely used in the delivery of antitumor drugs, antiviral drugs, antibacterial drugs, vaccines, genetic drugs, nuclear magnetic resonance contrast agents, etc., and are also widely used in injection, oral, ocular, and transdermal drug delivery.
Nano Drug Crystal
Many drugs are hardly soluble in water or even in organic solvents. Poor solubility often causes problems in the bioavailability of drugs, and the absorption varies greatly. Emulsification, micronization, cyclodextrin inclusion, addition of co-solvents, use of mixed solvents, surfactant solubilization and solid dispersion technologies can partially solve the problem of low bioavailability of insoluble drugs, but there are still a large number of drugs due to biological The utilization problem cannot be overcome and it is abandoned. Drug nanocrystals, also known as nano-suspensions, are a stably dispersed colloidal dispersion system formed by drug particles and a small amount of surfactant or polymer materials. Nano drug crystals can solve the dissolution problems of many poorly soluble drugs, and can improve the bioavailability to a certain extent. The FDA has approved a number of related products to market.