Hydrophobic nanocapsules

Photodimerization of stilbene in van der Waals nanocapsules has been studied [16]. para-Hexanoylcalix[4]arene nanocapsules (Figure 5.3) were used as hosts to carry out photodimerization of cis- and frans-stUbene to syn-tetraphenylcyclobutane. Singlecrystal X-ray diffraction studies were performed to define precisely the location of encapsulated stilbenes inside the capsule. It was shown that ds-stilbene stacks as Jt-Jt dimers located at the center of the capsule, whereas trans-stilbene does not form such a dimer. A possible configuration of two stilbene molecules in hydrophobic nanocapsules based on amphiphilic para-hexanoylcalix[4]arene is presented in Figure 5.4. Because the molecules are shifted with respect to each other, they cannot yield a good n-n stack, although local stabilization is possible. The authors suggested that the entire structure is a compromise between K-electron interaction of a trans-stilbene molecule with the host and n-n interactions of the two trans-stilbene molecules. 

Figure 5.4 Possible configuration of two stilbene molecules in hydrophobic nanocapsules based on amphiphilic para-hexanoylcalix[4]arene [16]. (Reproduced with permission.)...

KaanumaUe LS, Gibb CLD, Gibb BC, Ramamurthy V (2005) A hydrophobic nanocapsule controls the photophysics of aromatic molecules by suppressing their favored solution pathways. J Am Chem Soc 127 3674-3675... 

Block Copolymers are macromolecules which are composed of blocks usually in linear as it shown in Fig. 3.20, where it is illustrated a classical block copolymer. Main block copolymers are amphiphilic block copolymers having united hydrophilic blocks to hydrophobic blocks. Amphiphilic block copolymer have surfactant properties and form different kinds of associations, such as micelles, nanospheres, nanocapsules and polymersomes This tipe of association can act like excellent vehicles of several active principles. The composition, aggregate formation and the different applications of these materials have been reviewed [112], Figure 3.20 also illustrates the nanoparticulate drug delivery systems formed by amphiphilic block copolymers and their general characteristics. 

When the core is an oily liquid, the surrounding polymer is a single layer of polymer, and the vesicle is referred to as a nanocapsule. These systems have found utility in the encapsulation and delivery of hydrophobic drugs Polymers used for the formation of nanocapsules have typically included polyester homopolymers such as poly(D,L-lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone) PCL [112],... 

In this context, the chiral hyperbranched polyglycerols (-)-PG [Mn = 3000, with bis(2,3-dihydroxypropyl)undecenylamine as the initiator] and (+)-PG [Mn = 5500, with trimethylolpropane (TMP) as the initiator] were used. Esterification of the hydroxyl groups of these hyperbranched polyglycerols with hydrophobic alkyl chains as palmitoyl chloride, yielded amphiphilic molecular nanocapsules with reverse micelle-type architecture, in which approximately 50% of the hydroxyl groups were functionalized with palmitoyl chains [96-98]. These materials exhibit low polydispersity (Mw/Mn < 2), and the amphiphilic molecular nanocapsules are soluble in nonpolar solvents and irreversibly encapsulate various polar, water-soluble dye molecules in their hydrophilic interior by liquid-liquid extraction [96,98]. 

Liu S, Gibb BC (2008) High-definition self-assemblies driven by the hydrophobic effect synthesis and properties of a supramolecular nanocapsule. Chem Commun 3709-3716... 

It was found that the nanocapsules are formed in a miniemulsion process by a variety of monomers in the presence of larger amounts of a hydrophobic oil. Hydrophobic oil and monomer form a common miniemulsion before polymerization, whereas the polymer is immiscible with the oil and phase-separates throughout polymerization to form particles with a morphology consisting of a hollow polymer structure surrounding the oil. The differences in the hydro-philicity of the oil and the polymer turned out to be the driving force for the formation of nano capsules. 

The synthesis of nanocapsules can best be obtained in miniemulsion using different approaches [107], One possibility is based on the phase separation process within a droplet during the polymerization [108], Here, vinyl monomers were polymerized in the presence of a hydrophobic oil. During the polymerization, the polymer becomes insoluble in the oil, leading to a phase separation. With properly chosen physicochemical properties of monomer and encapsulated material, a polymeric shell surrounding the liquid core can be formed. 

Since the nineties of the last century, research groups around the world have explored the application of nanocapsules as nanoreactors, i.e. reaction vessels for chemical transformations, and the influence of different cavity effects." In this chapter the focus will mainly be on recent developments concerned with synthetic nanoreactors that can be obtained in a selective and controlled manner through the use of self-assembly principles and rational design, and on their application as catalytically active capsules for respective chemical reactions. For the sake of clarity, each specific type of nanoreactor will be discussed in a separate section. Particular types of nanocapsules to be reviewed include assemblies held together by hydrogen bonding, metal-ligand interactions and hydrophobic... 

Hydrophobic Effects as the Driving Force for the Self-Assembly of Nanocapsules... 

Additionally, the miniemulsion is excellently suited for the encapsulation of a variety of different materials, ranging from hydrophobic to hydrophilic, from solid to liquids, from inorganic to organic. The composite nanoparticles and nanocapsules can be functionalized at their surfaces and the encapsulated components can be released or not as desired. In the following review, the advantage of the miniemulsion process with many different examples will be presented. 

Nanocapsules can be formulated from a variety of synthetic or natural monomers or polymers by using different techniques in order to fulfil the requirements of various applications. Both, hydrophobic and hydrophilic liquids are of high interest for encapsulation. So, e.g., either sensitive or volatile substances, as drugs or fragrances have to be encapsulated and protected for applications with a sustained demand of the respective compound. DNA, proteins, peptides or other active substances can be encapsulated in order to target them to specific cells. A further benefit of the polymeric shell is the possibility to control the release from the composite particles and hence the concentration in the environment. 

Fig. 16 Capsule formation by phase separation, (a) Scheme a solution of monomer and hydrophobic oil (ie/t) is dispersed in an aqueous surfactant solution middle). Phase separation between the growing polymer and the oil occurs, leading to core shell morphology with encapsulated liquid, (b) Nanocapsules with hexadecane by phase separation [35]. (c) Encapsulation of Lucirin TPO [173] and (d) the fragrance 1,2-dimethyl-1-phenyl-butyramide [174]...

Another possibility for the formation of nanocapsules is to direct the polymerization reaction to the interface of nanodroplets. On the one hand, this can be realized either by using interfacially active initiators or water soluble initiators generating amphiphilic species, anchoring the growing polymeric chain to the interface. Here the monomer is only located in one, usually the dispersed phase. On the other hand, this can be realized if one hydrophilic monomer is present in the aqueous phase and the other hydrophobic monomer in the organic phase and these monomeric species only meet and react to a polymer at the interface. 

Romio AP, Sayer C, Araujo PHH, et al. (2009) Nanocapsules by miniemulsion polymerization with biodegradable surfactant and hydrophobe. Macromol Chem Phys 210 747-751 Zetterlund PB, Saka Y, Okubo M (2009) Gelation and hollow particle formation in nitroxide-mediated radical copolymeiization of styrene and divinylbenzene in miniemulsion. Macromol Chem Phys 210 140-149... 

Wilk KA, Zielinska K, Pietkiewicz 1, Skolucka N, Choromahska A, Rossowska 1, Garhiec A, and Saczko J. (2012). Photo-oxidative action in MCF-7 cancer cells induced hy hydrophobic cyanines loaded in biodegradahlemicroemulsion-templated nanocapsules. International Journal of Oncology, 41, 105-116. 

These authors concluded that the differences in the hydrophobicity of the oil and the polymer turned out to be the driving force for the formation of nanocapsules. Due to the pronounced difference of polarity of PMMA and hexadecane, the system was very well suited for the formation of nanocapsules. With more hydrophobic monomers such as styrene, however, it was more difQcult to create nanocapsules as the cohesion energy density of the polymer phase was close to that of the oil, and adjustment of parameters to influence the interfacial tensions and spreading coefficients became critical in order to form nanocapsules. The parameters studied were monomer concentration, type and amount of surfactant and initiators, and the addition of functional comonomers. For example, addition of 10 wt% acrylic acid as a comonomer in the miniemulsion leads to an increase in the number of close-to-perfect nanocapsules. 

Hydrophilic materials can be encapsulated with the inverse minianulsions by using interfacial polymerization such as polyaddition and polycondensation, radical, or anionic polymerization. Crespy et al. reported that silver nitrate was encapsulated and subsequently reduced to give silver nanoparticles inside the nanocapsules. The miniemulsions were prepared by anulsilying a solution of amines or alcohols in a polar solvent with cyclohexane as the nonpolar continuous phase. The addition of suitable hydrophobic diisocyanate or diisothiocyanate monomers to the continuous phase allows the polycondensation or the cross-linking reactions to occur at the interface of the droplets. By using different monomers, polyurea, polythiourea, or polyurethane nanocapsules can be formed. The waU thickness of the capsules can be directly tuned by the quantity of the reactants. The nature of the monomers and the continuous phase are the critical factors for the formation of the hollow capsules, which is explained by the interfacial properties of the systan. The resulting polymer nanocapsules could be subsequently dispersed in water. 

Miniemulsion is a special class of emulsion that is stabilized against coalescence by a surfactant and Ostwald ripening by an osmotic pressure agent, or costabilizer. Compared with conventional emulsion polymerization process, the miniemulsion polymerization process allows all types of monomers to be used in the formation of nanoparticles or nanocapsules, including those not miscible with the continuous phase. Each miniemulsion droplet can indeed be treated as a nanoreactor, and the colloidal stability of the miniemulsion ensures a perfect copy from the droplets to the final product. The versatility of polymerization process makes it possible to prepare nanocapsules with various types of core materials, such as hydrophilic or hydrophobic, liquid or solid, organic or inorganic materials. Different techniques can be used to initiate the capsule wall formation, such as radical, ionic polymerization, polyaddition, polycondensation, or phase separation from preformed polymers. 

Related to the generation of nanocapsules discussed above, is the appearance of rings or particles with single holes in hybrid system consisting of hydrophobic iron oxide, organic solvent, and polymer, probably in combination with KPS as initiator (see anchoring effect, Sect. 3.2). The emergence of these non-equilibrium structures is attributed to a delicate interplay of phase separation, viscosity, and solvent evaporation [191,192]. 

Romio AP, Sayer C, Araujo PHH et al (2009) Nanocapsules by miniemulsion polymerization with biodegradable surfactant and hydrophobe. Macromol Chem Phys 210 747-751... 

---