Synthesis of pH-sensitive amphotericin B–poly(ethylene glycol) conjugates and study of their controlled release in vitro

Toxicity Mechanisms of Amphotericin B and Its Neutralization by Conjugation with Arabinogalactan

“…However, the infusionrelated and cumulative toxicities, particularly nephrotoxicity (14,20,30), of AMB have resulted in reductions in the routine use of deoxycholate micellar AMB formulations and the development of less-toxic high-cost lipid AMB formulations (16,36). To develop a soluble, less-toxic, and less costly formulation, AMB has been conjugated with various soluble macromolecules (18,37,(47)(48)(49).We conjugated AMB with arabinogalactan (AG) (18), which significantly increased the water solubility of AMB, reduced its toxicity, and resulted in an efficacy similar to that of Fungizone (a deoxycholate micellar formulation) and AmBisome (a lipid-based formulation) (18). AMB-related toxicity is associated with the inductions of interleukin 1␤ (IL-1␤), tumor necrosis factor ␣ (TNF-␣), and apoptosis in organs.…”

“…However, the infusionrelated and cumulative toxicities, particularly nephrotoxicity (14,20,30), of AMB have resulted in reductions in the routine use of deoxycholate micellar AMB formulations and the development of less-toxic high-cost lipid AMB formulations (16,36). To develop a soluble, less-toxic, and less costly formulation, AMB has been conjugated with various soluble macromolecules (18,37,(47)(48)(49).…”

Doxorubicin-loaded aromatic imine-contained amphiphilic branched star polymer micelles: synthesis, self-assembly, and drug delivery

“…39,53 Thus, the anti-cancer drug DOX To identify whether this reaction occurred, the 1 H-NMR spectra of the reaction products were measured, and a typical 1 H-NMR spectrum of BP(DMAEMA-co-MAEBAco-DTDMA)(PMAGP) n -DOX is shown in Figure 5A; in addition to the characteristic proton signals of DMAEMA, MAEBA, DTDMA, and MAGP units, we can see aromatic proton signals of DOX at δ =7.20-7.72 ppm. Therefore, the covalent linking of DOX onto the core polymer chains was successful.…”

“…37 Obvious contribution of the reducing agent DTT to the drug release was not observed, because DOX is covalently bonded to the polymer chains via aromatic imine linkage, which is stable in the neutral aqueous solution. [36][37][38][39] However, when the release was performed in weak acidic solution, the influence of DTT on the release of DOX was observed; for example, when the release was conducted at pH =6.0 with and without DTT for 48 hours, different release rates were observed: 44 wt% (with DTT) and 34 wt% (without DTT) of DOX in micelles were released. The same phenomenon was observed for the release at pH =5.0, 56 wt% (with DTT) and 47 wt% (without DTT) of DOX in the drug carrier were released after 48 hours, because more imine bonds of the MAEBA units were exposed to an acidic environment after degradation of the BSP-H chains, which in turn, accelerated disassembly of the micelles.…”

“…34,35 In recent years, the imine linkers have gained significant attention, because several studies indicate that the aromatic imines with extended π-π conjugation can significantly improve the stability of imine linkages in water. [36][37][38][39] Therefore, we speculated that investigation of pH-responsive behaviors of drug carriers, in which the drug is covalently attached to the polymer backbone in the hydrophobic cores via aromatic imine linkage, should be interesting, and would help to enable design of a pH-triggered drug delivery system. The imine linkage has been widely employed in the preparation of shell or core cross-linked (SCL or CCL) micelles for improvement of micellar integrity and drug encapsulation stability.…”