Self-Assembled Drug Delivery Systems
In the first article on Pharmcosomes published in 1986, the researchers prepared the succinyl pindolol monostearoyl glyceride maleate pharmacosome. After being placed, the particle size can become larger, the chemical stability is good, and there is no degradation within 2 months, and the half-life of the drug substance is equivalent to that of the free drug; the oral drug substance is also basically the same as the free drug. The distribution of the drug in the body conforms to the one-compartment model, but unfortunately the author did not study it further. Because the explanation of pharmacosomes is too simple, there is no theory, and there are few related researches. For a long period of time, few people pay attention to this new dosage form. Before the concept of Pharmacosomes was proposed and formed, some chemists had prepared some lipid derivatives of polar drugs and observed the phenomenon that these amphiphilic molecules formed highly dispersed colloidal particles. However, they still call them “liposomes” and have not noticed the potential applications of this technology in drug delivery and new drug discovery, and have not developed them into new drug dosage forms.
Liposomes as drug carriers have certain defects. When liposomes are encapsulating drugs, especially polar drugs, the liposome carrier composed of phospholipids has no direct connection with the drugs, and the drug molecules are basically passive The encapsulation rate of the drug has always been a problem. At the same time, the drug easily leaks from the carrier and becomes free drug during the preparation, storage and use of liposome preparations. Especially in the body, the internal circulation of the carrier receptor and the impact of internal components (such as proteins and cells) easily leak out of the carrier. Therefore, there are not many drug-carrying liposomes that reach the target site, and it is difficult to obtain satisfactory therapeutic effects. . Other nanocarriers, such as Niosomes, Polymer nanoparticles, Solid lipid nanoparticles (SLNs), Polymer micelles, etc., have the same problem. In addition to the targeting problem caused by intravenous injection, traditional delivery carriers also have low encapsulation efficiency, small drug loading, and difficult drug control in other routes of administration, such as oral, mucosal, subcutaneous, and intramuscular injections. Pharmacists have designed many methods to solve the inherent defects of drug carriers, trying to increase the drug encapsulation rate and reduce drug leakage, but these methods are not satisfactory, or the technology used is very complicated and has no practical significance. Can a new way of drug delivery be designed to completely abandon the original idea of drug carrier or drug encapsulation, and the problem of encapsulation rate no longer exists. Based on this idea, scientists have put forward the concept of self-assembled drug delivery systems (SADDS) after a lot of research. According to the existing broad definition, SADDS is a self-assembly of amphiphilic prodrugs, covering a very wide range of drugs, prodrugs and self-assembly systems. This concept directly and profoundly expresses the characteristic “self-assembly” of the system, and extends it to the self-assembly system of any drug (prodrug), including various combinations of drugs and auxiliary molecules. Because this technology is based on molecular self-assembly, it generally forms a nano-scale structure, so it is often called a self-assembly or nano-assembly when it is specific to a certain drug.
Features of Self-Assembled Drug Delivery System
The design of SADDS inherited the idea of pharmacosomes design and broke through the concept of traditional pharmacy. Traditional pharmacy believes that excipients are “inert”, and preparations are obtained by combining active ingredients (drugs) and excipients in some way. Existing research results have proved that the outstanding advantages of SADDS include: 1. No or almost no excipients involved; 2. High drug loading, no longer the so-called “encapsulation rate”, 3. Because all prodrug molecules undergo “self-assembly” Therefore, the self-assembly is completely thermodynamically stable, with no drug leakage, and good stability; 4. Nano-level dispersion, can produce targeting in the body; 5. At the target site, a single prodrug molecule is dissociated from the aggregate and the prodrug is degraded into an active original medicine or active midbody. The controlled release effect can be obtained by controlling the dissociation and degradation rate; 6. It can be further functionalized, such as long circulation, tumor targeting, etc.; 7. The double-headed amphiphilic prodrug self-assembly system can also place different drugs in the same amphiphilic molecule, not only to achieve targeting, but also to obtain intracellular “cocktail” therapy.
Research Progress of Self-Assembled Drug Delivery System
The current research on SADDS mainly takes nucleoside analogue antiviral drugs, antituberculosis drugs, and antitumor drugs as model drugs, which are covalently combined with various long-chain lipid molecules to form amphiphilic prodrugs, and then through certain methods (mainly Injection method) disperse it into water to form highly dispersed aggregates. Aggregates are generally nanostructures, and their shapes can be vesicles, nanoparticles, nanotubes, etc. One of the advantages of nanoassemblies or nanostructures is that they can circulate in the blood relatively freely and can produce a targeting effect. Sometimes certain polymers can be added to increase the stability of the system. After intravenous injection, these self-assemblies of body were found to have strong targeting properties to the liver, lung, and spleen (which belong to the mononuclear macrophage system, MPS). After SADDS reaches the target site, it achieves a certain controlled release by controlling the rate of dissociation and degradation of the amphiphilic prodrug from the self-assembly to the original drug. Oral or subcutaneous injection also shows targeted distribution of tissues (such as the lymphatic system) and organs. After adding some hydrophilic polymers to the self-assembly system, the cycle time can be appropriately extended.