Anticancer drugs targeted therapy through the blood-brain barrier: drug, chemical modification or nanoparticles. Quite small and carrier size, which limits the number of modified nano-carrier molecules, making it difficult to achieve the appropriate combination of balance. Adsorption-mediated endocytosis also becomes a hot topic, including the electrostatic interaction between the negatively charged cell membrane and positively charged ligands at the BBB (mainly sialic acid). The system of carrier-mediated transporters includes glucose transporter 1. Studies have shown that liposome surface parcels can be instrumental. Mannose, but not B mannose derivative, can induce transport across the BBB. Cation transporter-mediated choline derivatives coated nanoparticles are transported by brain-derived endothelial cells faster than uncoated nanoparticles, possibly due to the lipophilicity of choline derivatives. The BBB-specific expression of folate receptor transporters can be surface-modified by folic acid flexible multi-star nanoparticles. Some hydrophilic surfactants, especially Tween class, interact with the BBB surface. Twain flexible multi-coated nanoparticles show more potential for drug transit to the brain compared to PEG-coated nanoparticles. Surfactant toxicity, non-biocompatibility, and increased BBB permeability causing destruction of tight junctions are important issues.
3 Conclusion
Several strategies can improve the ability of anticancer drugs to penetrate the BBB:
(1) Fat-soluble drugs via passive diffusion, limited to small molecules;
(2) Development of prodrugs to bypass the BBB transporter mechanism, but the high selectivity of the transport mechanism limits this strategy;
(3) Development of drug-loaded nanocarriers that can disrupt the tumor BBB. Nanoparticles hold the most potential for drug delivery to brain tumors. Minimally invasive and highly selective strategies for drug delivery to brain tumors must take advantage of physiological and permeability differences. Colloidal systems (nanoparticles) through modification can enhance brain targeting, increasing drug efficacy while reducing adverse reactions. Technical issues in development include the complexity of nanoparticle preparation and targeted nanoparticles, increasing the risk of adverse reactions; advantages include increased drug reaching the target and selective enhancement, and multiple drugs reaching the same position as possible. Creating a molecular toolbox to enable nanoparticles to effectively wrap drugs and deliver them to brain tumors is necessary, assembling molecular-level structures into space and chemically controllable ordered structures. Multifunctional delivery vectors must contain positively charged (cationic) components to enhance vascular uptake, vascular targeting, and inter-cellular transport of reagents and drugs. Achieving the effectiveness and selectivity of nano carriers capable of carrying anticancer drugs is a very complex entity. Nanocarriers can encapsulate anticancer drugs in the core of a polymer film layer, with BBB-targeting molecules on the surface and enhanced molecular modifications of transporters, enough positive charge to increase intake by brain tumor blood vessels, and inhibitors to suppress BBB and multi-drug resistance mechanisms produced by tumor cells.
Therefore, the ideal target brain tumor treatment drug nanoparticle delivery system (Figure 2) has the following characteristics:
(1) Selective targeting of BBB lesions;
(2) Contains key efflux pump inhibitors that can partially hydrolyze;
(3) Transports drugs through the brain vascular system and transfers them to the target, which is brain tumor cells.
Nanosystems with this diversity, but to make extensive use of this technique, a better understanding of the biophysical mechanism of interaction between nanoparticles and living organisms, biochemical mechanisms, and physiological mechanisms is needed. Challenges include changes in clear brain tumor and disease-related BBB properties; modification of drugs or drug carriers as targeting agents and transit enhancers. Antibodies are selective, but their size and potential immunogenicity limit their spread and use in organizations, such as Tf and its receptor, presenting similar problems. The most promising vectors are small molecules that can be used as BBB targeting agents and transit enhancers, stable in physiological medium, easy to synthesize, and with large drug loading. However, a generic design uniquely applicable in various environments and purposes of targeting vectors is unrealistic.
The agent, the blood drying Shao boots, improves choice: Tian pickled Yi transport enhancer, mouth BBB transporter + ~ II) R inhibitors: hydrolysis in order to reduce the drugs across the BBB efflux from the endothelial cells of Figure 2 nano particle delivery system structure model compiled from: Juillerat-JeanneretL,. The targeted delivery of cancer drugs across the blood - brain barrier: chemical modifications of drugs or drug-nanoparticles? [J]. Drug Discov Today, 2008,13 (23/24): 1099-1106.