Short CommunicationTunable morphology of lipid/chitosan particle assemblies
Graphical abstract
Influence of the lipid membrane morphology (i.e. lipid discs, or lipid vesicles) on the lipid/chitosan particle assemblies.
Introduction
Chitosan particles have been widely investigated in the past decades due to their ability to transport, protect drugs, and target specific sites [1]. Numerous studies have been dedicated to their synthesis via an ionic gelation process with the aim of obtaining colloids with controlled sizes and size distributions [2], [3], [4], [5]. However, limitations regarding their colloidal physicochemical and biological properties are quickly reached in in vivo conditions (e.g., in the presence of relatively high amounts of salts or proteins, pH variation) [6]. To overcome these limitations, their surface modification by a lipid membrane is particularly appealing in the drug delivery area. Indeed, this surface modification provides several interesting advantages as a drug release from assemblies not only controlled by their core (polymer degradation), but also by their lipid shell (diffusional barrier) [7], [8], [9], [10], [11], [12], [13], [14]. Furthermore, the resulting biomimetic lipid surface [15] can easily be modified by hydrophilic poly(ethylene glycol) chains and targeting ligands (leading to long-circulating targeted assemblies). Concerning the polymer core, it brings a structural integrity and stability to this lipid coat (versus hollow liposomes). Such core-shell assemblies (named LipoParticles) have already been examined with synthetic polymer cores (e.g., based on poly(lactic acid) [16], [17], [18], poly(lactic-co-glycolic acid) [19], [20], and polystyrene [21], [22]).
This core-shell nano-organization (in which each particle is covered with a lipid membrane) has previously been observed by microscopy [16], [21], [23], [24], [25]. However, in the case of CS particle cores, the final structures obtained so far in the literature appear to be much less controlled. Several synthesis methods of these assemblies with CS particles have been developed such as reverse phase emulsion [26], [27], lyophilisation (mixture of CS particles with a vesicle suspension followed by freeze drying) [28], or lipid film hydration by a CS particle suspension [29], [30], [31]. More recent studies [32], [33], [34] focused on the preparation of more individualized and better defined assemblies. Nevertheless, this has required a supplementary extrusion step of assemblies through polycarbonate membranes with pore sizes in the sub-micrometer range after the lipid film hydration step by a CS particle suspension. Moreover, TEM images of resulting assemblies may raise some reservations about their morphology [32], [33], [34].
The lipid film hydration method by a suspension of synthetic polymer particles has previously been compared to the spontaneous reorganization of lipid vesicles onto particles to synthesize LipoParticles [21]. This study revealed that the second process was the most suitable to obtain assemblies with satisfactory sizes and size distributions. This explains why this procedure (i.e., “two-step method”) [13] was the most reported in the literature. However, no work has been carried out so far on lipid/CS particle assemblies prepared by this way. Moreover, to the best of our knowledge no work about the influence of the lipid membrane morphology on the lipid adsorption process has been reported in the literature despite the understanding aspects about the lipid adsorption, and the opportunity to tune the final morphology of assemblies. Consequently, the aim of this work is to form and to characterize assemblies obtained by adding two types of preformed lipid membranes (classical vesicles or discs) to CS particle suspensions. The influence of each type is examined on the size, size distribution, zeta potential, and morphology of final assemblies.
Section snippets
Results and discussion
As previously mentioned, CS particles and lipid membranes were independently prepared before mixing. CS particles were obtained via an ionic gelation process by using tripolyphosphate as ionic crosslinking agent. The details of experimental conditions are described in a previous work [2]. Resulting CS particles are spherical, with a reproducible sub-micrometer size, and a narrow size distribution. Concerning the preparation of lipid membranes, it firstly requires the formation of multilamellar
Conclusions
This study has shown for the first time that the formation of lipid/CS particle assemblies with relatively satisfactory sizes and size distributions can be obtained via a spontaneous membrane adsorption procedure for further consideration of resulting assemblies as drug delivery systems. The lipid surface modification presents great interest as an increase of colloidal stability in physiological pH values. Moreover, it has been displayed in this work that the final morphology of assemblies
Acknowledgements
This work was financially supported by a grant from the French Ministry of Higher Education and Research. The authors gratefully acknowledge the “CTµ” (Centre Technologique des Microstructures de l’Université Lyon 1) platform for the access to TEM, and cryo-TEM.
Conflicts of interest
There are no conflicts to declare.
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