Nanospheres and nanocapsules

Both nanospheres and nanocapsules are prepared from either a polymerization reaction of dispersed monomers or from a solvent dispersion procedure using preformed polymers. In many instances, the latter procedure using preformed polymer is desirable, as potential reactions between drug and monomer are avoided and the potential toxicity of residual monomers, surfactant, and initiator is reduced [37], The final properties of nanoparticles, such as their size, morphology, drug loading, release characteristics, and biodisti-bution, are all influenced by the method of preparation [38],... 

The procedure chosen for the preparation of lipid complexes of AmB was nanoprecipitation. This procedure has been developed in our laboratory for a number of years and can be applied to the formulation of a number of different colloidal systems liposomes, microemulsions, polymeric nanoparticles (nanospheres and nanocapsules), complexes, and pure drug particles (14-16). Briefly, the substances of interest are dissolved in a solvent A and this solution is poured into a nonsolvent B of the substance that is miscible with the solvent A. As the solvent diffuses, the dissolved material is stranded as small particles, typically 100 to 400 nm in diameter. The solvent is usually an alcohol, acetone, or tetrahydrofuran and the nonsolvent A is usually water or aqueous buffer, with or without a hydrophilic surfactant to improve colloid stability after formation. Solvent A can be removed by evaporation under vacuum, which can also be used to concentrate the suspension. The concentration of the substance of interest in the organic solvent and the proportions of the two solvents are the main parameters influencing the final size of the particles. For liposomes, this method is similar to the ethanol injection technique proposed by Batzii and Korn in 1973 (17), which is however limited to 40 mM of lipids in ethanol and 10% of ethanol in final aqueous suspension. 

The drug can be dissolved, entrapped, encapsulated, or attached to a nanoparticle matrix, and depending upon the method of preparation, nanoparticles, nanospheres, and nanocapsules can be obtained (Soppimath et al. 2001). 

Allowing self-assembly of CDs resulting in the spontaneous formation of nanosize carriers in the form of nanospheres and nanocapsules... 

Particle sizes of nanocapsules are mostly affected by the size of the oil droplet formed during the preparation along with the molar concentration and nature of amphiphilic CD. Nanospheres, on the other hand, are not significantly affected by amphiphilic CD concentration and can be formed with very high concentrations of amphiphilic CDs. The modification site of the CD (primary or secondary face) is influential for nanosphere size since modifications on the secondary face result in a larger surface area. The presence and concentration of a surfactant such as Pluronic F68 do not affect the particle size of nanospheres and nanocapsules [80], Nano-... 

Drug loading into amphiphilic nanospheres and nanocapsules is governed by the loading technique used. Amphiphilic CD nanoparticles can be loaded with the following techniques ... 

Drug-loaded nanoparticles were also evaluated for their safety and efficacy. Paclitaxel-encapsulated 6-O-CAPRO-p-CD nanospheres and nanocapsules were evaluated for their physical stability in a one-month period in aqueous dispersion form with repeated particle size and zeta potential measurements and AFM imaging to evaluate recrystallization in aqueous medium. Paclitaxel-loaded amphiphilic CD nanoparticles were found to be physically stable for a period of one month whereas recrystallization occurs within minutes when diluted for intravenous (IV) infusion [85], Finally, paclitaxel-loaded amphiphilic nanoparticles were demonstrated to show similar anticancer efficacy against MCF-7 cells when compared to paclitaxel solution in a cremophor vehicle [85],... 

FIGURE 9 In vitro release profile of tamoxifen from B-CDC6 nanospheres and nanocapsules before and after gamma sterilization. (Reprinted from E. Memisoglu-Bilensoy and A. A. Hincal, International Journal of Pharmaceutics, 311,203-208,2006. Copyright 2006 with permission from Elsevier.)... 

Memi oglu-Bilensoy, E., Sen, M., and Hincal, A. A. (2006), Effect of drug physicochemical properties on in vitro characteristics of amphiphilic cyclodextrin nanospheres and nanocapsules, J. Microencapsul., 23(1), 59-68. 

Polymer nanoparticles including nanospheres and nanocapsules (Fig. 1) can be prepared according to numerous methods that have been developed over the last 30 years. The development of these methods occurred in several steps. Historically, the first nanoparticles proposed as carriers for therapeutic applications were made of gelatin and cross-linked albumin. Then, to avoid the use of proteins that may stimulate the immune system and to limit the toxicity of the cross-linking agents, nanoparticles made from synthetic polymers were developed. At first, the nanoparticles were made by emulsion polymerization of acrylamide and by dispersion polymerization of methylmethacry-late.f These nanoparticles were proposed as adjuvants for vaccines. However, since they were made of non-biodegradable polymers, these nanoparticles were rapidly substituted by particles made of biodegradable... 

Fig. 3 Summary of the different methods to prepare nanospheres and nanocapsules from a polymer. W/O water-in-oil, 0/W oil-in-water, W/O/W water-in-oil-in-water.

Suspensions of liposomes, microspheres and microcapsules, and nanospheres and nanocapsules formed from a variety of polymers or proteins, as discussed in section 8.6.3 form a new class of pharmaceutical suspension in which physical stability is paramount. It is important that on injection these carrier systems do not aggregate, as this will change the effective size and the fate of the particles. The exception to this is the deliberate flocculation of latex particles administered to the eye, where aggregation leads to agglomerated... 

An example for a nanoparticle system undergoing a phase transition of the matrix is given by nanospheres and nanocapsules from poly-e-caprolactone (PCL) formed by the emulsion-diffusion technique. In this case, the mechanism of particle formation in an o/w emulsion is based on the diffusion of an organic solvent into the continuous phase followed by the deposition of the polymer around an oil droplet (Fig. 20). 

The structure of nanoparticles is similar to that of microparticles but their diameter is less than 1 pm. Similarly, two types of nanoparticle can be distinguished nanospheres and nanocapsules. 

Nanosuspensions consist of the pure poorly water-soluble drug without any matrix material suspended in dispersion. It is sub-micron colloidal dispersion of pure particles of drug stabilized by surfactants. By formulating nanosuspensions, problems associated with the delivery of poorly water-soluble drugs and poorly water-soluble and lipid-soluble drugs can be solved. Nanosuspensions differ from nanoparticles, " which are polymeric colloidal carriers of drugs (nanospheres and nanocapsules), and from solid-lipid nanoparticles, which are lipidic carriers of drug. 

The main family of bioerodible polymers is represented by poly(alkylcya-noacrylate)s (PACA). These polymers have a long history since 1947 as adhesives, especially in areas where a fast cure rate is needed. Polymerisation of alkylcyanoacrylates (ACA) can be initiated in the presence of bases as weak as the hydroxyl ions of water. The propagation rate decreases when the size of the lateral alkyl chain increases. As polymerisation can be very fast, ACAs have been used as surgical glue, as tissue adhesive and for embolisation purposes. As shown in Section 4.4.6, ACAs have also been used extensively for preparing nanospheres and nanocapsules for drug delivery. 

Nanoparticles, i.e. particles with a size usually in the range 50-1000 nm, have drawn the attention of researchers designing drug-delivery systems that can be injected intravenously owing to their small size. Nanoparticle is a general name for nanospheres and nanocapsules. Nanospheres have a matrix-type structure, whereas nanocapsules are hollow and have a liquid core surrounded by a polymeric wall, as illustrated in Figure 4.34. 

Teixeira M, Alonso MJ, Pinto MM et al (2005) Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone. Fur J Pharm Biopharm 59 491-500... 

NPs can be differentiated as nanospheres and nanocapsules (Figure 17.1). Nanospheres can be defined as matrix-type colloidal particles in which a drug is entrapped, dissolved, chemically bound or adsorbed to the constituent polymer matrix, while nanocapsules are vesicular systems with a typical core-shell structure in which the drug is mainly confined to a reservoir or within a cavity surroxmded by a polymer membrane. This drug can also be carried on the capsule surface or imbibed in the polymeric membrane [40]. 

Finally the solvent evaporation process, that is generally the last step of the synthesis process, must be considered as it can cause an increase in the final particle size if the evaporation is carried out in a rotating evaporator imder moderate vacuum, a very limited variation is observed for both PCL and PEGylated copolymer, both in nanosphere and nanocapsule form, as shown in Figure 9.14 (compare also Figure 9.21 in Section 9.3 for an example with non-quenched particles) [72, 106 (supp. info.), 107]. In the case of loaded particles, different behaviors can be obtained in the case of PEGylated... 

Figure 9.20 The data show that the inlet jet Reynolds number (Re ) is a good scale up criterion for geometrically similar scaled CIJ mixers CIJ-d2 data are also shown to evidence that a variation of the inlet tube/chamber diameter ratio may influence the final particle size. Both PEGylated copolymer nanospheres and nanocapsules are shown, evidencing different dependence on Re. quenched samples (quench ratio = 1) in the upper graph, non-quenched in the lower graph, measured after solvent (acetone) evaporation. Nanocapsules (containing Miglyol , MR=1.26) , scale down , reference (CIJ-dl) , scale up A, CIJ-d2. Polymer nanospheres , scale down O, reference (ClJ-dl) O, scale up , CIJ-d2.

It has been shown that a power law type can be effective in relating the particle size to the main operating variables, both for solid nanospheres and nanocapsule either with a liquid or fatty core. 

S.S. Guterres, M.P. Alves, and A.R. Pohlmann, Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insights, 2 (2), 147-157, 2007. 

B. Stella, S. Arpicco, E Rocco, V. Marsaud, J.M. Renoir, L. Cattel, and P. Couvreur, Encapsulation of gemcitabine lipophilic derivatives into polycyanoacrylate nanospheres and nanocapsules. International Journal of Pharmaceutics, 344 (1-2), 71-77,2007. 

I. Valente, L.J. Del Valle, M.T. Casas, L. Franco, A. Rodriguez-Galdn, J. Puiggali, and D.L. Marchisio, Nanospheres and nanocapsules of amphiphilic copolymers constituted by methoxypolyethylene glycol cyanoacrylate and hexadecyl cyanoacrylate units, eXPRESS... 

Valente, E. Celasco, D.L. Marchisio, and A.A. Barresi, Nemoprecipitation in confined impinging jets mixers Production, characterization and scede up of PEGylated nanospheres and nanocapsules for pharmaceutical use. Chemical Engineering Science, 77, 217-227, 2012. 

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