Colloids and Surfaces A: Physicochemical and Engineering Aspects
Stability and physicochemical characteristics of PLGA, PLGA:poloxamer and PLGA:poloxamine blend nanoparticles: A comparative study
Introduction
Poly(d,l-lactic-co-glycolic acid) (PLGA) micro- and nanospheres have been extensively used as biodegradable colloidal drug carriers [1], [2]. However, the rapid removal of intravenously administered colloidal drug carriers by the mononuclear phagocytic system (MPS), comprised mainly of the hepatic Kupffer cells of the liver and the macrophages of the spleen, has been identified as the major obstacle to the efficient targeting of colloidal carriers to target sites [3]. Nevertheless, the recognition of the carriers by the MPS can be significantly altered if the surface of the colloidal particles is modified using polyethylene oxide (PEO)/polypropylene oxide (PPO) block copolymers of the poloxamer and poloxamine series [4]. These copolymers are well known for their safety and biocompatibility. In addition, PEO/PPO/PEO block copolymers show a wide range of hydrophilicity/hydrophobicity as a function of the PEO:PPO ratio, so that it is possible to achieve different degrees of particle hydration [5]. The poloxamer and poloxamine copolymers are bound to the nanosphere surface by the hydrophobic interaction of the PPO chains while the hydrophilic PEO chains protrude into the surrounding medium creating a steric barrier [6], [7]. It has been suggested that this barrier prevents or restricts the adsorption of plasma proteins onto the particle surface decreasing recognition by liver and spleen macrophages [8], [9]. Further research has indicated that it is not only a reduction in the adsorption of plasma components but also the selective uptake of certain plasma components acting as dysopsonins that can prevent recognition by macrophages [10]. Therefore, the coating of nanoparticle carriers by this kind of ABA block copolymer has become a successful strategy in recent years to develop drug-delivery systems. In addition, recent work suggests improvements in developing colloidal drug carriers when the poloxamers and poloxamines are incorporated into the nanoparticles during preparation instead of adsorbing them onto the bare PLGA particles [11]. These new nanocarries containing hydrophilic PEO derivatives have allowed the encapsulating of plasmid DNA [12]. It has been also demonstrated that the presence of this type of polymer helps neutralize the acidity generated in the course of PLGA degradation, preserving DNA structural integrity and thus its biological activity [13]. Moreover, the presence of the polyoxyethylene derivative has been found to exert a positive effect on the release characteristics of nanoparticles [12].
Csaba et al. [11], using 1H NMR and differential scanning calorimetry (DCS), reported that poloxamers and poloxamines were effectively incorporated into the particle composition when preparing the systems by an optimized emulsification-solvent diffusion technique. However, 1H NMR and DCS techniques cannot distinguish the distribution of the non-ionic copolymers—that is, when located mainly inside the particles, preferably at the interface or at both sites. The analysis of some physical characteristics such as stability or electrokinetic behavior of colloidal systems has proved useful in ascertaining the final surface properties of nanoparticles [14]. Hence, these colloidal characteristics for PLGA:poloxamer (Pluronic F68) and PLGA:poloxamine (Tetronic 904) blend nanoparticles were studied in the present paper. In addition, we have found no comparative studies concerning the final physicochemical properties of PLGA nanoparticles or those resulting from incorporating these amphiphilic copolymers into the nanospheres during production. Thus, the aim of the present work is a comparative characterization of physical properties of the particles related to their electrophoretic mobility and colloidal stability.
Section snippets
Materials
The polymer poly(d,l-lactic acid/glycolic acid) 50:50 was purchased from Boehringer-Ingelheim under the commercial name of Resomer® RG 503. The poloxamer Pluronic® F68 was from Sigma–Aldrich. The poloxamine Tetronic 904 was kindly donated by BASCOM Belgium. Fig. 1 shows the chemical structure and main characteristics of both surfactants. According to the HLB values, poloxamer F68 presents a more hydrophilic character than does poloxamine 904. All other solvents and chemicals used were of the
Main particle characteristics
Three type of systems – the pure PLGA and two blend formulations which differed in the surfactant used in their preparation (Table 1) – were used to compare the influence of the different surfaces on the final physicochemical properties of the nanoparticles. Table 1 shows the incorporated amount of poloxamer F68 and poloxamine T904 with respect to the total quantity of polymers in the particle (data from reference [11]). It can be seen that the most hydrophobic surfactant, poloxamine T904, was
Conclusions
Parameters describing the electrokinetic behavior and the stability of pure PLGA nanoparticles and the two blend formulations PLGA:poloxamer and PLGA:poloxamine have been determined in this work. Electrophoretic mobility measurements showed that this technique distinguishes the differences among the three samples studied and also helps to corroborate stability results. Mobility data confirmed the difference in the degree of hydrophobicity of the two blend formulations.
With respect to stability,
Acknowledgements
Authors thank the financial support given by the projects MAT2003-01257 and SAF2003-08765 from the Comisión Interministerial de Ciencia y Tecnología (CICYT), Spain.
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Present address: Department of Chemistry and Applied Biosciences, ETH-Honggerberg, HCI J398, Wolfgang-Pauli Str 10 CH-8093, Zurich, Switzerland.