“…In addition, the weak interactions and steric repulsion interactions (electrostatic) among the TPGS molecules from nano-micelles improved the structural integrity of the self-assembly nanomicelles. 27 These data suggest that HTPM can maintain high stability in the simulated GI fluids. Figure 3 Stability of HTPM and in vitro drug release profiles of HF and HTPM in the simulated gastrointestinal fluids.…”
Section: Resultsmentioning
confidence: 83%
“…A recent investigation has shown that the ZP of drug-free TPGS polymer micelles was negative. 27 Herein, HTPM were positively charged, with a ZP of 14.40 ± 0.1 mV ( Figure 2B ), which may be due to the H + accumulated by amino in the molecule structure of HF. The positively charged HTPM could interact with the negatively charged intestinal mucus due to electrostatic interactions, thereby contributing to the prolonged intestinal retention time.…”
Section: Resultsmentioning
confidence: 93%
“…TPGS not only shows outstanding drug delivery ability because of the special amphiphilic structure, but it can also be functionalized as an excellent solubilizer, bioavailability enhancer, and stabilizer of hydrophobic drugs due to its large surface area and bulky structure. 27 Herein, HTPM have been successfully prepared by the thin-film hydration method ( Figure 1 ), as reported previously. 17 For oral delivery, the particle size and surface charge of the self-assembled micelles appear to be the most important parameters, which greatly influence the transport route of micelles through the intestinal epithelium membrane and determine their stability.…”
Section: Resultsmentioning
confidence: 99%
“…It has been reported that TPGS could self-assemble to form nano-micelles with critical micellar concentration (CMC) of 13.91 μg/mL. 27 Herein, HTPM were prepared using the thin-film hydration method as reported previously. 17 Briefly, HF and TPGS were first dissolved in methanol to obtain the transparent organic phase.…”
Background
Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.
Methods
Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.
Results
Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.
Conclusion
Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.
“…In addition, the weak interactions and steric repulsion interactions (electrostatic) among the TPGS molecules from nano-micelles improved the structural integrity of the self-assembly nanomicelles. 27 These data suggest that HTPM can maintain high stability in the simulated GI fluids. Figure 3 Stability of HTPM and in vitro drug release profiles of HF and HTPM in the simulated gastrointestinal fluids.…”
Section: Resultsmentioning
confidence: 83%
“…A recent investigation has shown that the ZP of drug-free TPGS polymer micelles was negative. 27 Herein, HTPM were positively charged, with a ZP of 14.40 ± 0.1 mV ( Figure 2B ), which may be due to the H + accumulated by amino in the molecule structure of HF. The positively charged HTPM could interact with the negatively charged intestinal mucus due to electrostatic interactions, thereby contributing to the prolonged intestinal retention time.…”
Section: Resultsmentioning
confidence: 93%
“…TPGS not only shows outstanding drug delivery ability because of the special amphiphilic structure, but it can also be functionalized as an excellent solubilizer, bioavailability enhancer, and stabilizer of hydrophobic drugs due to its large surface area and bulky structure. 27 Herein, HTPM have been successfully prepared by the thin-film hydration method ( Figure 1 ), as reported previously. 17 For oral delivery, the particle size and surface charge of the self-assembled micelles appear to be the most important parameters, which greatly influence the transport route of micelles through the intestinal epithelium membrane and determine their stability.…”
Section: Resultsmentioning
confidence: 99%
“…It has been reported that TPGS could self-assemble to form nano-micelles with critical micellar concentration (CMC) of 13.91 μg/mL. 27 Herein, HTPM were prepared using the thin-film hydration method as reported previously. 17 Briefly, HF and TPGS were first dissolved in methanol to obtain the transparent organic phase.…”
Background
Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.
Methods
Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.
Results
Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.
Conclusion
Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.
“…Structure-modified HA with hydrophobic molecules could form grafted amphiphilic copolymers and be used for micelle construction. Vitamin E succinate (VES), as a natural hydrophobic vitamin E derivative, could not only serve as hydrophobic residue, but also possess potential antitumor activity (Fan et al, 2021;Farooq et al, 2021;Puig-Rigall et al, 2021). Therefore, the HA-g-VES-grated copolymer is suitable for copolymer micelle construction.…”
The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
