Coating and Functionalization Strategies for Nanogels and Nanoparticles for Selective Drug Delivery
Abstract
:1. Introduction
2. Nanoparticles and Nanogels
2.1. Definition and Properties
2.2. Synthesis and Formation Methods
2.3. Polymer Functionalization for Nanoparticles Synthesis
- The activation of esters under mild conditions to form amide bonds. This technique represents one of the most interesting strategies for polymer functionalization: esters [40] are very flexible for different kinds of functionalization while amides are very versatile linkages in organic chemistry thanks to their stability in chemical environments and compatibility with different functionalities.
- Click chemistry, which allows the introduction of compatible click functional groups in pre-existing molecules that are able to activate molecules and polymers [41]. This process is usually performed with copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC process), but it can also be realized with a copper-free strain promoted azide–alkyne process to overcome the cytotoxicity of the CuAAC reaction [42].This technique is stereospecific and generates non-toxic byproducts that can be easily removed. Moreover, functionalization with azide and alkyne groups offers the possibility to link very different molecules and improve material properties and compatibility.
- Thiol chemistry represents another important process in this field thanks to the great available functional thiols and reactions in which they can participate [43,44]. They have radical- and light-mediated reactivity with carbon–carbon double bonds, and this allows the advantages of click reactions to be combined with those of photoinitiated reactions [45]. In this way, it is possible to obtain quantitative yields, high reaction rates, and easy product recovery. At the same time, the method based on electrophile and nucleophile interactions allows operation in mild reaction conditions, has great compatibility with different functional groups, high conversion, and very good possibilities of application in different fields such as biomedicine.
- The addition of alcohols, amines and thiols to isocyanates [46] represents a possible effective strategy in polymer functionalization thanks to fast reaction kinetics, the stability of isocyanates toward radicals, and the good yields. However, their application is limited by the toxicity of isocyanate and the instability of final mixtures containing isocyanate and polymer mixtures.
- Imine [47] and oxime [48,49] linkages have an important role in the field of macromolecular modification reactions. They allow the bond reversibility in the case of imine linkage thanks to the equilibrium of this molecule and in the case of oxime under aqueous acid conditions. This functionalization method can be tuned according to the desired application: the obtained linkage can be hydrolytically stable or unstable according to the need, in order to preserve the functionalization or to release the grafted molecule.
- Ring-opening reactions are a classical and versatile method in polymer science [50]. They allow the ring of strained heterocycles to be opened and for desired heteroatoms to be introduced on the polymer backbone [51,52]. The most commonly employed functional groups in this kind of synthesis are the epoxides, but in recent years ring-opening modifications involving aziridines and azlactones have been reported.
- Multicomponent reactions (MCRs) [53] are an upcoming synthesis methodology which are of great interest because of their atom economy. Their advantage lie in their ability to introduce a high degree of functional complexity in a single modification step [54]. These kinds of reactions include isocyanide-based MCRs, non-isocyanide-based MCRs, and MCRs catalyzed by organometallic species.
3. Targeted Drug Delivery: Selectivity of the Delivery Process and Its Applications
4. Available Strategies to Coat Nanoparticles
4.1. Polymers
4.2. An Organic Solution: Cell Membrane Coating
4.3. Proteins and Antibodies: A Very Promising Possibility
4.4. Novel Strategy: Hybridized DNA Structure
5. Conclusions
Conflicts of Interest
References
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Applications of NPs Drug Delivery Systems | Advantages |
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Tumors | Passive targeting promoted by enhanced permeability and retention (EPR) effect: accumulation on target site is favored |
Diabetes | Less-invasive route for the delivery of insulin and improvement in the drug delivery |
Cardiovascular Diseases | Development of regenerative medicine and of the possibility to manage this kind of disease |
CNS Injuries | Possibility to overcome biological barriers, reaching the CNS and having a less-invasive delivery system |
Coating Strategies | Advantages | Disadvantages |
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Polymers |
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Cell Membranes |
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Proteins and Antibodies |
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Hybridized DNA Structure |
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Pinelli, F.; Perale, G.; Rossi, F. Coating and Functionalization Strategies for Nanogels and Nanoparticles for Selective Drug Delivery. Gels 2020, 6, 6. https://doi.org/10.3390/gels6010006
Pinelli F, Perale G, Rossi F. Coating and Functionalization Strategies for Nanogels and Nanoparticles for Selective Drug Delivery. Gels. 2020; 6(1):6. https://doi.org/10.3390/gels6010006
Chicago/Turabian StylePinelli, Filippo, Giuseppe Perale, and Filippo Rossi. 2020. "Coating and Functionalization Strategies for Nanogels and Nanoparticles for Selective Drug Delivery" Gels 6, no. 1: 6. https://doi.org/10.3390/gels6010006