Large‐Scale Preparation of Polymer Nanocarriers by High‐Pressure Microfluidization

Abstract

by dispersion, suspension emulsion, or miniemulsion polymerization, while the preparation of polymer nanocarriers made from preformed polymers usually occurs by coacervation methods such as salting out, [13] emulsification-diffusion, [14] nanoprecipitation, and supercritical fluid technology. [15,16] Among those different preparation techniques, miniemulsion is particularly attractive due to its ability to prepare nanocarriers from either mono mer or polymer while allowing for the efficient loading of large doses of therapeutic agents, which can be lipophilic and/or hydrophilic compounds. [17] Furthermore, miniemulsion provides the opportunity to finely tune particle size distribution while preparing emulsion with high solid content of polymers. [18][19][20] The crosslinking of polymer-containing nanodroplets formed by miniemulsion is a particularly attractive method to produce nanocarriers (Figure 1). Hollow nanocapsules can be prepared by a polyaddition or polycondensation reaction occurring at the droplets interface. [21] In order to prepare nanocarriers, the polymer is dissolved in a good solvent and emulsified with an immiscible nonsolvent forming the continuous phase. After the emulsification, a crosslinking agent, soluble in the continuous phase, is added to the emulsion and the poly addition or polycondensation reaction between the polymer and crosslinking agent occurs at the surface of the droplet. When the reaction kinetic is fast enough, a shell insoluble in both phases can be formed at the interface. [22] To control the size and size distribution of the nanocapsules prepared by the polyaddition/polycondensation reaction at the droplet interface, it is critical to control the preparation of the miniemulsion used as a precursor. The two main factors leading to the broadening of the size distribution of the nanodroplets during miniemulsion are (i) Ostwald ripening and (ii) coalescence of the droplets occurring through collision. The coalescence could be controlled by the addition of an appropriate surfactant, which provides electrostatic or steric stabilization thus preventing droplet coalescence. Ostwald ripening is affected by multiple factors such as droplet size, Laplace pressure, polydispersity, and solubility of the dispersed phase in the continuous phase. In general, Ostwald ripening could be limited by the addition of compounds increasing the osmotic pressure in the system. These chemicals need to be highly insoluble in the continuous phase but completely soluble in the Nanocapsules Polymer nanocarriers are used as transport modules in the design of the next generation of drug delivery technology. However, the applicability of nanocarrier-based technology depends strongly on our ability to precisely control and reproduce their synthesis on a large scale because their properties and performances are strongly dependent on their size and shape. Fundamental studies and practical applications of polymer nanocarriers are hampered by the difficulty of using the current methods to produce monodispersed ...

Coencapsulation of Polyphenols and Anthocyanins from Blueberry Pomace by Double Emulsion Stabilized by Whey Proteins: Effect of Homogenization Parameters

“…Characterization of particle size distribution would also provide additional insights. The smallest values of average diameter reported in previous studies, which generally ranged from 200–550 nm for simple emulsions [ 20 , 21 , 38 , 40 , 41 ], are comparable to the values obtained in the present work with double emulsions.…”

“…For simplification, the term coalescence is used to refer to two distinct processes (coalescence and Ostwald ripening) as they both lead to an increase in particle size but cannot be easily distinguished [ 39 ]. Overprocessing can be attributed to the limited ability of the emulsifier to rapidly adsorb onto the newly created surfaces and to the high Brownian motion, which increase the probability of collisions leading to droplet coalescence at high microfluidization pressure [ 40 ]. When the timescale of collisions is shorter than that of adsorption, the interfaces of the newly formed oil droplets cannot be fully covered by the emulsifier (WPI in our study), resulting in insufficient droplet stabilization and increased coalescence [ 21 , 40 ].…”

“…Overprocessing can be attributed to the limited ability of the emulsifier to rapidly adsorb onto the newly created surfaces and to the high Brownian motion, which increase the probability of collisions leading to droplet coalescence at high microfluidization pressure [ 40 ]. When the timescale of collisions is shorter than that of adsorption, the interfaces of the newly formed oil droplets cannot be fully covered by the emulsifier (WPI in our study), resulting in insufficient droplet stabilization and increased coalescence [ 21 , 40 ]. Denaturation of the whey proteins may be a contributing factor, further decreasing the ability of WPI to effectively stabilize the droplets at 200 MPa.…”

“…To date, overprocessing during high-pressure emulsification has been reported mostly in simple emulsions, mainly O/W [ 20 , 21 , 38 ] and more rarely W/O [ 40 ]. The pressure ranges at which particle size was found to increase in these studies vary from 63–84 MPa [ 21 ], 69–105 MPa [ 37 ], 70–105 MPa [ 20 ], 90–150 MPa [ 38 ] and 150–300 MPa [ 41 ].…”

Polysaccharide-Based pH-Responsive Nanocapsules Prepared with Bio-Orthogonal Chemistry and Their Use as Responsive Delivery Systems

“…For example, the reaction between multifunctional alcohols, amines, or thiols and diisocyanate compounds has shown the efficient encapsulation of a variety of payloads in polyurea, polyurethane, or polythiourea nanocapsules. 15 , 16 However, such reactions involving nucleophiles like alcohols and amines that are also present in sensitive biomolecules used as payloads could lead to side reactions and cause a partial or total decrease in the efficacy of the payload.…”