Anionic Liposomes in Contact with Cationic Chitosan Particles
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nionic Liposomes in Contact with Cationic Chitosan Particles A. A. Efimovaa,*, A. S. Popova, and G. G. Krivtsovb a
Lomonosov Moscow State University, Moscow, 119991 Russia Research Institute of Vaccines and Sera, Moscow, 105064 Russia *e-mail: [email protected]
b Mechnikov
Received November 9, 2020; revised November 9, 2020; accepted November 18, 2020
Abstract—Nanoparticles of ionically cross-linked chitosan have been prepared from the linear polymer with weight-average molecular mass Mw of 30000, 63000, or 300000 and the molar content of primary amino groups of 0.85. Multi-liposomal complexes have been obtained via electrostatic adsorption of anionic liposomes on the surface of cationic chitosan particles. The effect of the chitosan molecular weight on the size of the final complexes and their stability in a water–salt media have been studied. The conditions for the formation of multi-liposomal complexes with size in the range of 250–450 nm have been determined. We have proposed to use linear chitosan with Mw of 30000 and 63000 to obtain multi-liposomal complexes. The size of the resulting constructions allows them to enter cells via the passive transport mechanism through enlarged pores in blood capillaries in inflammatory foci and tumors. Keywords: cross-linked chitosan, electrostatic complex, nanoparticle, liposome, passive transport
DOI: 10.1134/S1070363220110225 INTRODUCTION Liposomes which have been actively used in recent decades as containers for hydrophobic, hydrophilic, and amphiphilic compounds are special among the numerous systems for the delivery of bioactive substances [1–7]. The immobilization of dozens of anionic liposomes on the surface of a colloid carrier increases the efficiency of drug delivery and opens new possibilities for the creation of multifunctional biologically active drugs [8–12]. We have recently proposed a simple method for the immobilization of anionic liposomes on the surface of cationic chitosan particles via direct electrostatic adsorption, without preliminary modification of both components, which greatly reduces the time and material costs for multi-liposomal complexes obtaining. The resulting conjugate has been found stable at physiological values of ionic strength and effectively interacted with cells, subsequently releasing drug from the liposomes [13, 14]. When creating multi-liposomal constructs, it seems important to choose their base – chitosan microgel particles. The size of the initial microgel particle depends on the chitosan molecular weight [15]. Systematic studies of the effect of the degree of polymerization of chitosan on the size of the final multi-liposomal complexes and their aggregate stability have not been carried out so far. At the same time, such information is extremely important
for determining the conditions for the formation of multiliposomal complexes and for obtaining conjugates with size in the range of 250–450 nm. Such containers can enter the cells by means of passive transport through enlarged pores in blood capillaries in inflammat
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