They can be divided into two main groups: a) soluble (CDPS) and b) insoluble (CDPIS) polymers. The structure of insoluble polymers of the mechanochemical reactions generally is more compact, with fewer and shorter hydrophilic arms than the products of the solution reactions.Ĭyclodextrin (CD) polymers are covalently linked hollow structures that are a network of less flexible macrocycles. Solid reactants not only reduce the chance of hydrolysis of multifunctional reactants or side reactions, but the spatial proximity of macrocycles also reduces the length of the spacing formed by the crosslinker. The in-soluble polymer synthesis is also more efficient when using the same molar ratio of the reagents as the solution reaction. In the case of thiolated CD derivatives, the absence of solvents results in significant suppression of the thiol group oxidation, too. Regioselective syntheses of per-6-amino and alkylthio-CD derivatives or insol-uble cyclodextrin polymers and nanosponges are good examples of what a greener technology can offer through solvent-free reaction conditions. When the reaction yields a good guest co-product, solvent-free conditions can be slower than in solu-tion conditions. A mechanochemical reaction generally has a higher reagent utilization rate.

The limited molecular movements in solid-state allow the preparation of CD derivatives, which are difficult to produce under solvent reaction conditions. The lack of solvents can make syntheses more economical and greener. The sweetest point of mechanochemistry is the reduced demand or complete elimination of solvents from the synthesis. In many cases, the solubility of both the starting material and the product in the same solvent differs significantly. However, many authors also refer to the formation of non-covalent bonds, such as the formation of inclusion complexes or metal–organic networks, as reactions or synthesis, which makes it difficult to classify the technical papers. Complex formation faces similar challenges in that it involves interacting materials with conflicting properties. In many cases, the synthesis of CD derivatives requires high-boiling solvents, whereas the product isolation from the aqueous methods often requires energy-intensive processes. We highlighted that neo-vesicles promote the penetration of ATV in endothelial cells of the BBB, presumably due to the low fusogenicity of Lip- β -CDs.Ĭyclodextrin (CD) derivatives are a challenge, mainly due to solubility problems. It was demonstrated that mixed vesicles comprised of phosphatidylcholine (POPC) and LipCDs were able to encapsulate atazanavir (ATV), a well-known protease inhibitor used as an antiretroviral drug against HIV. As a result, we introduced a convergent synthesis for a family of lipophosphoramidyl permethylated β -CDs (Lip- β -CDs) with various chain lengths. Such cyclodextrin derivatives were used to prepare vesicles and to study their ability to vectorize a drug through the BBB. Our goal is to propose an optimized chemical synthesis of amphiphilic cyclodextrin, which remains a challenging task which commonly leads to only a low-milligram level of the high purity compound. Amphiphilic cyclodextrins can form self-assemblies whose nanoparticles have a 100-nm-diameter range and are thus able to encapsulate drugs for controlled release. In this context, polymer nanoparticles are a promising alternative to bypass the BBB and carry drugs to brain cells.

The blood brain barrier (BBB) prevents the majority of therapeutic drugs from reaching the brain following intravenous or oral administration.

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