Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

Abstract

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against Tityus serrulatus Scorpion Venom

“…Thus, the co-solvent addition in the NE formulations have been described as an interesting and promising way to produce small-droplet sized NEs [ 48 ]. Indeed, the co-solvent reduces the oil/water interfacial tension and decrease the segregation grade among the specific non-polar compounds, improving the diffusion rate of surfactants to the aqueous phase, at the phase inversion moment [ 35 , 48 , 49 ]. Therefore, the N -methyl-pyrrolidone (NMP) was used as a co-solvent in this study due to its ability to dissolve SPC and improve its miscibility in the oily phase of the NEs.…”

“…These compositions are interesting and promising for producing pharmaceutical emulsion systems. Indeed, the greater SPC amount (75% w / w ) in the surfactant mixture certainly produces more biocompatible emulsion systems [ 35 , 47 ]. However, produce self-assembled NEs using SPC is not an easy task.…”

“…All the achieved NE formulations pointed out in the PPTD exhibited surfactant content superior to 30% w / w ( Figure 1 c). This amount of surfactant is an important obstacle to produce biocompatible and non-hemolytic NEs [ 35 , 48 , 49 ]. In addition, these formulations showed PdI values >0.4 (data non showed).…”

“…The phase transition was reported as an interesting approach for preparing nanoemulsions by simple dilution of microemulsions with water altering the surfactant arrangement in the oil/water interface [ 33 ], from transitional bicontinuous structures [ 34 ]. In anterior studies, we have reported a similar strategy to produce biocompatible O/W nanoemulsions from suitable dilutions of lyotropic lamellar LCs [ 35 ]. According the type of the used surfactant, the phase transition strategy can incorporate concepts of phase inversion temperature (PIT), phase inversion composition (PIC), and catastrophic phase inversion (CPI).…”

Development and Characterization of Nanoemulsion Containing Almond Oil, Biodegradable Polymer and Propranolol as Potential Treatment in Hemangioma

“…PTD consisting of oil, water and surfactant mixture were constructed using the oil method . According to the best HLB determined previously, the ratio of Span 80/Tween 80 was fixed at 95:5 on the weight basis.…”