The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine–modified chitosan (SC) was synthesized as a potential AKI kidney–targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule–1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)–sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.
Lysozyme-glucose stearic acid monoester (HEL-GE) conjugate was prepared through the Maillard reaction as an antibacterial emulsifier. The molar ratio of GE to HEL was 1:1. The isoelectric point was 6-7, which is lower than that of native HEL. Spectroscopic studies indicated that the alpha-helix content was slightly lower but the conformation around Trp had not changed and that the surface of the conjugate was covered with the GE moiety. The conjugate maintained approximately 53-57% of the enzymatic activity of native HEL at 40-60 degrees C and exhibited considerable resistance to proteolysis. The denaturation temperature of the conjugate was approximately 74 degrees C, somewhat higher than that of control HEL, whereas the enthalpy was about one-third of that of control HEL. The emulsifying activity of the conjugate and the emulsion stability were much enhanced compared to those of native HEL, and the conjugate maintained approximately 70% of the bactericidal activity.
Water-in-soybean oil-in-water (W/O/W) emulsions with an internal water phase content of 10-30% (vol/vol) were prepared by a two-step emulsification method using microfluidization and straight-through microchannel (MC) emulsification. A straight-through MC is a silicon array of micrometer-sized through-holes running through the plate. Microfluidization produced water-in-oil (W/O) emulsions with submicron water droplets of 0.15-0.26 µm in average diameter (d av,w/o ) and 42-53% in CV (CV w/o ) using tetraglycerin monolaurate condensed ricinoleic acid esters (TGCR) and polyglycerin polycondensed ricinoleic acid esters (PGPR) as surfactants dissolved in the oil phase. The d av,w/o and viscosity of the W/O emulsions increased with an increase in internal water phase content. Straightthrough MC emulsification was performed using the W/O emulsions as the to-be-dispersed phase and polyoxyethylene (20) sorbitan monooleate (Tween ® 80) as a surfactant dissolved in the external water phase. Monodisperse W/O/W emulsions with d av,w/o/w of 39.0-41.0 µm and CV w/o/w below 5% were successfully formed from a straight-through MC with an oblong section (42.8 × 13.3 µm), using the TGCR-containing systems. The d av,w/o/w of the monodisperse W/O/W emulsions decreased as the internal water phase content increased because of the increase in viscosity of the to-be-dispersed phase. Little leakage of the internal water droplets and no droplet coalescence or droplet breakdown were observed during straight-through MC emulsification.Paper no. J10903 in JAOCS 82, 65-71 (January 2005).KEY WORDS: Droplet formation, internal water phase content, microfluidization, monodisperse emulsion, oblong straightthrough microchannel, straight-through microchannel emulsification, viscosity, water-in-oil-in-water emulsion.
Vitiligo is a depigmentation disease that seriously affects the physical health, mental health and quality of life of a patient. Therapeutic aim at control immunoreaction by relieving oxidative stress. Unfortunately, the cuticle barrier function and lack of specific accumulation lead to unsatisfactory therapeutic outcomes and side effects. The introduction and innovation of nanotechnology offers inspiration and clues for the development of new strategies to treat vitiligo. However, not many studies have been done to interrogate how nanotechnology can be used for vitiligo treatment. In this review, we summarize and analyze recent studies involving nano-drug delivery systems for the treatment of vitiligo, with a special emphasis on liposomes, niosomes, nanohydrogel and nanoparticles. These studies made significant progress by either increasing drug loading efficiency or enhancing penetration. Based on these studies, there are three proposed principles for topical nano-drug delivery systems treatment of vitiligo including the promotion of transdermal penetration, enhancement of drug retention and facilitation of melanin regeneration. The presentation of these ideas may provide inspirations for the future development of topical drug delivery systems that will conquer vitiligo.
Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine–proline–valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP–tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.
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