In this work, we provide proof-of-concept of formation, physical characteristics and potential use as a drug delivery formulation of Pickering emulsions (PE) obtained by a novel method that combines nanoprecipitation with subsequent spontaneous emulsification process. To this end, pre-formed ultra-small (d.∼10 nm) nanoprecipitated nanoparticles of hydrophobic derivatives of cashew tree gum grafted with polylactide (CGPLAP), were conceived to stabilize Pickering emulsions obtained by spontaneous emulsification. These were also loaded with Amphotericin B (AmB), a drug of low oral bioavailability used in the therapy of neglected diseases such as leishmaniasis. The graft reaction was performed in two CG/PLA molar ratio conditions (1:1 and 1:10). Emulsions were prepared by adding the organic phase (Miglyol 812) in the aqueous phase (nanoprecipitated CGPLAP), resulting the immediate emulsion formation. The isolation by centrifugation does not destabilize or separate the nanoparticles from oil droplets of the PE emulsion. Emulsions with CGPLAP 1:1 presented unimodal distributions at different CGPLA concentration, lower values in size and PDI and the best stability over time. The AmB was incorporated in the emulsions with a process efficiency of 21-47%, as determined by UV-vis. AmB in CGPLAP emulsions is in less aggregated state than observed in commercial AmB formulation.

Nanoparticles are produced by means of polyelectrolyte complexation (PEC) of oppositely charged polycationic chitosan (CH) with polyanionic polysaccharide extracted from Sterculia striata exudates (rhamnogalacturonoglycan (RG)-type polysaccharide). The nanoparticles formed with low-molar-mass CH are larger than those formed with high-molar-mass CH. This behavior is in contrast with that previously observed for other systems and may be attributed to different mechanisms related to the association of CH with RG of higher persistence length chain than that of CH. Nanoparticles harnessed with a charge ratio (n(+)/n(-)) of <1 are smaller than particles with an excess of polycations. Particles with hydrodynamic sizes smaller than 100nm are achieved using a polyelectrolyte concentration of 10(-4)gmL(-1) and charge ratio (n(+)/n(-)) of <1. The CH/RG nanoparticles are associated with chloroquine (CQ) with an efficiency of 28% and release it for up to ∼60% within ∼10h, whereas in the latter, only ∼40% of the CQ was released after 24h. The main factor that influenced drug release rate is the nanoparticle charge ratio.

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Stable oil nanocapsules based on acetylated Sterculia striata polysaccharide (ASSP) were produced without the use of a surfactant, and derivatives of ASSP with four different degrees of substitution (DS) were synthesised. The data revealed that only derivatives with high DS were able to produce nanocapsules (NC), which exhibited monomodal size distribution profiles with a Z-average particle size,-potential, and polydispersity index (PDI) that were dependent on ASSP DS and concentration. Nanocapsules were loaded with amphotericin B (AMB) with encapsulation efficiencies (EE%) thatwere dependent on drug and ASSP concentrations and DS. A maximum EE% value of 99.2%was achieved, and the loaded AMBwas found to be in amonomeric form, evenwith a concentration one hundredfold higher than that usually observed for commercial AMB aqueous solutions. Loaded nanocapsules show an in vitro controlled release of AMB. As the monomeric AMB state decreased drug toxicity, ASSP nanocapsules loaded with AMB (NC1.68) have potential for use as a drug delivery system. AMB loaded NC 1.68 keeps its activity against 5 strains of Candida albicans tested.

This is a repository copy of Self-assembling cashew gum-graft-polylactide copolymer nanoparticles as a potential amphotericin B delivery matrix.