Pharmaceutical Nanotechnology
Polymer-based nanocapsules for drug delivery

https://doi.org/10.1016/j.ijpharm.2009.10.018Get rights and content

Abstract

A review of the state of knowledge on nanocapsules prepared from preformed polymers as active substances carriers is presented. This entails a general review of the different preparation methods: nanoprecipitation, emulsion–diffusion, double emulsification, emulsion-coacervation, polymer-coating and layer-by-layer, from the point of view of the methodological and mechanistic aspects involved, encapsulation of the active substance and the raw materials used. Similarly, a comparative analysis is given of the size, zeta-potential, dispersion pH, shell thickness, encapsulation efficiency, active substance release, stability and in vivo and in vitro pharmacological performances, using as basis the data reported in the different research works published. Consequently, the information obtained allows establishing criteria for selecting a method for preparation of nanocapsules according to its advantages, limitations and behaviours as a drug carrier.

Introduction

Generally, nanoparticles are defined as solid colloidal particles that include both nanospheres and nanocapsules. They can be prepared by both polymerization methods and synthesis with preformed polymers (Fattal and Vauthier, 2002, Vauthier and Bouchemal, 2008). One of their fundamental characteristics is their size, which is generally taken to be around 5–10 nm with an upper size limit of ∼1000 nm, although the range generally obtained is 100–500 nm (Quintanar et al., 1998a).

As asserted by different authors, nanoparticulated systems show promise as active vectors due to their capacity to release drugs (Cruz et al., 2006, Amaral et al., 2007); their subcellular size allows relatively higher intracellular uptake than other particulate systems (Furtado et al., 2001a, Furtado et al., 2001b); they can improve the stability of active substances (Ourique et al., 2008) and can be biocompatible with tissue and cells when synthesized from materials that are either biocompatible or biodegradable (Guinebretière et al., 2002).

Other advantages of nanoencapsulated systems as active substance carriers include high drug encapsulation efficiency due to optimized drug solubility in the core, low polymer content compared to other nanoparticulated systems such as nanospheres, drug polymeric shell protection against degradation factors like pH and light and the reduction of tissue irritation due to the polymeric shell (Pinto et al., 2006a, Anton et al., 2008).

Polymeric nanoparticles have been extensively studied as drug carriers in the pharmaceutical field (Legrand et al., 1999, Barratt, 2000, Chaubal, 2004, Sinha et al., 2004, Letchford and Burt, 2007) and different research teams have published reviews about the nanoparticle formation mechanisms (Quintanar et al., 1998a, Moinard-Checot et al., 2006), the classification of nanoparticulated systems (Letchford and Burt, 2007) and the techniques for preparation of nanocapsules (Moinard-Checot et al., 2006, Pinto et al., 2006a, Vauthier and Bouchemal, 2008). As a contribution to updating the state of knowledge, the present review focuses on nanocapsules obtained from preformed polymers, using prototype cases, among others, to provide illustrations. The aspects studied are mean size, zeta-potential, encapsulating efficiency, active release, nanodispersion stability and in vivo and in vitro pharmacological performance behaviours.

Section snippets

Nanocapsule definition

First of all the nanocapsules can be likened to vesicular systems in which a drug is confined in a cavity consisting of an inner liquid core surrounded by a polymeric membrane (Quintanar et al., 1998a). However, seen from a general level, they can be defined as nano-vesicular systems that exhibit a typical core-shell structure in which the drug is confined to a reservoir or within a cavity surrounded by a polymer membrane or coating (Letchford and Burt, 2007, Anton et al., 2008). The cavity can

Methods for the preparation of nanocapsules and their fundamental mechanisms

Generally, there are six classical methods for the preparation of nanocapsules: nanoprecipitation, emulsion–diffusion, double emulsification, emulsion-coacervation, polymer-coating and layer-by-layer (Fig. 2). Nevertheless, other methods have been used such as emulsion–evaporation and the methodologies for the preparation of polymer liposomes.

Regarding to the solvent emulsion–evaporation method, it has been used for the preparation of nanocapsules (Pisani et al., 2008). However, the latter

Behaviour of nanocapsules as drug delivery systems

The current section of this review will focus on the behaviour of nanocapsules in relation to their size, zeta-potential, dispersion pH, shell thickness, encapsulation efficiency, drug release, stability and in vivo and in vitro performances as a function of their preparation method. These properties have been chosen because they are those most frequently sought.

To this end, more than seventy research works available in electronic databases (Science direct® and Springerlink®) have been studied.

Discussion and concluding remarks

Nanoencapsulation is an attractive strategy for the vectorization of a variety of active substances. As is shown in Table 2, although with different objectives, research has been focused on antineoplastics, antiinflammatories, immunosupresants, antigens, hormones, antivirals, antibacterials, antifungals, diuretics, antipneumocystics and vitamins, among others.

According to different authors, nanocapsules used as drug carriers can mask unpleasant tastes, provide controlled release properties and

Acknowledgements

C.E. Mora-Huertas was supported by a grant from Departamento Administrativo de Ciencia, Tecnología e Innovación – Colciencias (Colombia). She also acknowledges to Universidad Nacional de Colombia.

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