Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy

Ma, Wei-Cong; Zhang, Qing; Li, Hui; Larregieu, Caroline A.; Zhang, Na; Chu, Ting; Jin, Hui; Mao, Shengjun

doi:10.1016/j.ijpharm.2013.04.023

Cited by 18 publications

(5 citation statements)

References 32 publications

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“…Based on previous experiments (Ma et al, 2013;Đorđević et al, 2013), the soybean lecithin was selected as the main emulsifier for nanoemulsion preparation in the present study.…”

Section: Preparation and Characterization Of Nanoemulsionsmentioning

confidence: 99%

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation

Đorđević

Cekić

Savić

et al. 2015

International Journal of Pharmaceutics

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This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution <0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.

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“…Based on previous experiments (Ma et al, 2013;Đorđević et al, 2013), the soybean lecithin was selected as the main emulsifier for nanoemulsion preparation in the present study.…”

Section: Preparation and Characterization Of Nanoemulsionsmentioning

confidence: 99%

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation

Đorđević

Cekić

Savić

et al. 2015

International Journal of Pharmaceutics

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“…Functionalization of PMs with folate is an already existing trend by which we can target the massively expressed FRs located externally on the cancerous cells encompassing breast, ovarian, and uterine cancers. [80][81][82] Furthermore, a subtype of FR namely, FR alpha (FRa) was found to have higher affinity towards folic acid and some other analogue molecules. 83 This receptor is located within the cellular plasma membranes attached to glycosylphosphatidylinositol molecule which can facilitate the entrance of FA or FA-decorated micelles via receptor-mediated endocytosis.…”

Section: Folate Receptors (Frs)mentioning

confidence: 99%

“…87 Pluronic F68 is a synthetic and amphiphilic polymer approved by the FDA. 82 It is well known to possess a sandwich-like structure comprising two hydrophilic poly(ethylene oxide) (PEO) blocks with a poly(propylene oxide) (PPO) block located within them. Pluronic F68 was selected to be the drug carrier owing to its potential to suppress P-gp (P-glycoprotein), and hence reducing drug efflux, while FA was selected to be the targeting ligand due to its ability to join FR and enhance cellular uptake via receptor-mediated endocytosis.…”

Section: Folate Receptors (Frs)mentioning

confidence: 99%

Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine

Agwa,

Marzouk,

Sabra

2024

RSC Adv.

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“…Even when the content of 8-arm-PEG20k-DFO and 8arm-PEG40k-DFO was added to the concentration of 5mg/mL (equal to 1.6 mM or 0.8 mM of DFO), the hemolysis percentage of the 8-arm-PEG-DFO conjugate was still below 1.2%. The quite low hemolysis activity indicated that the macromolecular conjugates had excellent biocompatibility for intravenous administration [30,31]. ; (B).…”

Section: In Vitro Hemolysis Testmentioning

confidence: 99%

A Novel Star Like Eight-Arm Polyethylene Glycol-Deferoxamine Conjugate for Iron Overload Therapy

Yang

Liu

et al. 2020

Pharmaceutics

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The traditional iron chelator deferoxamine (DFO) has been widely used in the treatment of iron overload disease. However, DFO has congenital disadvantages, including a very short circular time and non-negligible toxicity. Herein, we designed a novel multi-arm conjugate for prolonging DFO duration in vivo and reducing cytotoxicity. The star-like 8-arm-polyethylene glycol (8-arm-PEG) was used as the macromolecular scaffold, and DFO molecules were bound to the terminals of the PEG branches via amide bonds. The conjugates displayed comparable iron binding ability to the free DFO. Furthermore, these macromolecule conjugates could significantly reduce the cytotoxicity of the free DFO, and showed satisfactory iron clearance capability in the iron overloaded macrophage RAW 246.7. The plasma half-life of the 8-arm-PEG-DFO conjugate was about 190 times than that of DFO when applied to an intravenously administered rat model. In conclusion, research indicated that these star-like PEG-based conjugates could be promising candidates as long circulating, less toxic iron chelators.Pharmaceutics 2020, 12, 329 2 of 13 pharmacokinetics (PK) of DFO was thus regarded as a promising approach to promote therapeutic efficacy and mitigate the side effects.Many attempts have been conducted by conjugating DFO to a water-soluble polymer to improve its PK properties. For example, the hyper-branched glycerol was used to form conjugates with DFO, which made it possible to chelate iron efficiently and prolong the circulation time of API in the blood [7,15,16]. Specially, the circulation half-life (t 1/2 ) of DFO was increased by up to 44 h in mice, a 484-fold increase compared to native DFO. Nevertheless, it has not yet been pursued in clinical study, probably due to the limitations of the excipients and cumbersome synthesis methods. Other DFO macromolecular conjugates, such as polyrotaxane-DFO and dextran-DFO conjugate, also showed efficacies in iron chelation and rather low cell toxicities [17,18]. However, the reported t 1/2 was prolonged to be a moderate level (~1 h). The PEG has been used in the many products since it was approved by the FDA as a pharmaceutical polymer material [19][20][21]. The PEGylation conjugates provide a solution to increase the stability of drugs and prolong their blood circulation. Tremendous efforts have been devoted to create PEG-based solutions for improving the defect of the DFO. In previous studies, the DFO was conjugated to the copolymer with the PEG side chain or the PEG based three-arm macromolecule, for designing the biocompatible, long-circulating macromolecule iron-chelator [22,23]. These polymer conjugates, however, suffered from the wide molecular range and low loading efficacy of API, making the following translations difficult. Recently, multi-armed PEGs have gained much attention in both academic and industrial fields, due to their superiority in drug-loading efficacies compared to the traditional linear PEG [24][25][26]. Herein, we successfully synthesized and designed an 8-arm-polyethylene glycol-...

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Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy

Cited by 18 publications

References 32 publications

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation

Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine

A Novel Star Like Eight-Arm Polyethylene Glycol-Deferoxamine Conjugate for Iron Overload Therapy

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