Dexamethasone palmitate
(Synonyms: 地塞米松棕榈酸酯; DXP) 目录号 : GC38573
地塞米松棕榈酸酯 (DXP) 是地塞米松 (DXM) 的亲脂性前药，是一种糖皮质激素受体激动剂，与糖皮质激素受体的亲和力比 DXM 低 47 倍。
Cas No.:14899-36-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
RAW 264.7 cells |
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Preparation Method |
After 24 h of incubation with 100 μg/mL Dexamethasone palmitate, cell supernatants were collected and frozen at 20 C until analysis was performed. Cells were detached and counted. |
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Reaction Conditions |
100 μg/mL Dexamethasone palmitate，24h |
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Applications |
A decrease of cytokines concentration was clearly observed resulting from the anti-inflammatory effect of Dexamethasone palmitate-NPs. |
| Animal experiment [2]: | |
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Animal models |
Brown Norway male rats |
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Preparation Method |
Choroidal neovascularization (CNV) was induced with a 532-nm argon laser photocoagulator in the right eyes of the anesthetized animals. Following the laser procedure on day 0 supratemporal IVT injections of either the vehicle [phosphate- buffered saline (PBS); 0.8% Dexamethasone palmitate emulsion (4 μg Dexamethasone palmitate; 0.5 μL), and Kenacort were administered to the treated right eyes. |
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Dosage form |
4 μg Dexamethasone palmitate；0.5 μL |
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Applications |
Rat efficacy data demonstrated that IVT administration of Dexamethasone palmitate emulsions is effective for delivering therapeutic concentrations of DXM at the level of the choroid. |
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References: [1]. Romero IA, Radewicz K, et,al. Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells. Neurosci Lett. 2003 Jun 26;344(2):112-6. doi: 10.1016/s0304-3940(03)00348-3. PMID: 12782340. [2]. Daull P, Paterson CA, et,al. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema. J Ocul Pharmacol Ther. 2013 Mar;29(2):258-69. doi: 10.1089/jop.2012.0044. Epub 2013 Jan 18. PMID: 23331052. |
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Dexamethasone palmitate (DXP), a lipophilic prodrug of Dexamethasone (DXM), is a glucocorticoid receptor agonist with a 47-fold lower affinity for the glucocorticoid receptor than DXM[1].
A decrease of cytokines concentration was clearly observed resulting from the anti-inflammatory effect of Dexamethasone palmitate-NPs .the MCP-1 chemokine was strongly and significantly reduced by Dexamethasone palmitate-NPs and TNFα in presence of LPS[2].
Rat efficacy data demonstrated that IVT administration of Dexamethasone palmitate emulsions is effective for delivering therapeutic concentrations of DXM at the level of the choroid[2]. Dexamethasone palmitate-NPs could benefit from the typical high vascular permeability of inflamed joints and diffuse passively to accumulate and be retained in the diseased sites. This accumulation in inflamed joints led to improvement of the joint inflammation and eventually disease remission[3].
References:
[1]:Romero IA, Radewicz K, Jubin E, Michel CC, Greenwood J, Couraud PO, Adamson P. Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells. Neurosci Lett. 2003 Jun 26;344(2):112-6. doi: 10.1016/s0304-3940(03)00348-3. PMID: 12782340.
[2]: Daull P, Paterson CA, Kuppermann BD, Garrigue JS. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema. J Ocul Pharmacol Ther. 2013 Mar;29(2):258-69. doi: 10.1089/jop.2012.0044. Epub 2013 Jan 18. PMID: 23331052.
[3]: Lorscheider M, Tsapis N, Ur-Rehman M, Gaudin F, Stolfa I, Abreu S, Mura S, Chaminade P, Espeli M, Fattal E. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis. J Control Release. 2019 Feb 28;296:179-189. doi: 10.1016/j.jconrel.2019.01.015. Epub 2019 Jan 16. PMID: 30659904.
地塞米松棕榈酸酯 (DXP) 是地塞米松 (DXM) 的亲脂性前药，是一种糖皮质激素受体激动剂，与糖皮质激素受体的亲和力比 DXM 低 47 倍[1]。
由于地塞米松棕榈酸酯-NP 的抗炎作用，清楚地观察到细胞因子浓度降低。在 LPS 存在的情况下，MCP-1 趋化因子被地塞米松棕榈酸酯-NP 和 TNFα 强烈而显着地降低[2 ].
大鼠疗效数据表明，IVT 给予地塞米松棕榈酸酯乳剂可有效地在脉络膜水平递送治疗浓度的 DXM[2]。地塞米松棕榈酸酯-NPs 可以受益于发炎关节典型的高血管通透性，并被动扩散以积聚并保留在患病部位。这种在发炎关节中的积累导致关节炎症的改善，并最终缓解了疾病[3]。
| Cas No. | 14899-36-6 | SDF | |
| 别名 | 地塞米松棕榈酸酯; DXP | ||
| Canonical SMILES | C[C@@]12[C@](C[C@@H](C)[C@]2(O)C(COC(CCCCCCCCCCCCCCC)=O)=O)([H])[C@@]3([H])[C@@](F)([C@@]4(C(CC3)=CC(C=C4)=O)C)[C@@H](O)C1 | ||
| 分子式 | C38H59FO6 | 分子量 | 630.87 |
| 溶解度 | DMSO: 250 mg/mL (396.28 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5851 mL | 7.9256 mL | 15.8511 mL |
| 5 mM | 0.317 mL | 1.5851 mL | 3.1702 mL |
| 10 mM | 0.1585 mL | 0.7926 mL | 1.5851 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis
J Control Release 2019 Feb 28;296:179-189.PMID:30659904DOI:10.1016/j.jconrel.2019.01.015.
Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by joint inflammation, bone and cartilage erosion. The use of glucocorticoids in the treatment of RA is hampered by significant side effects induced by their unfavorable pharmacokinetics. Delivering glucocorticoids by means of nanotechnologies is promising but the encapsulation of highly crystalline and poorly water-soluble drugs results in poor loading and low stability. We report here the design of 130 nm nanoparticles made of solely Dexamethasone palmitate, stabilized by polyethylene glycol-linked phospholipids displaying a negative zeta potential (-55 mV), high entrapment efficiency and stability over 21 days under storage at 4 °C. X ray diffraction showed no crystallization of the drug. When incubated in serum, nanoparticles released free dexamethasone which explains the in vitro anti-inflammatory effect on LPS-activated RAW 264.7 macrophages. Moreover, we demonstrate in a murine collagen-induced arthritis model the improved therapeutic efficacy of these nanoparticles. Their passive accumulation in arthritic joints leads to disease remission and recovery of the joint structure at a dose of 1 mg/kg dexamethasone, without any adverse effects. Dexamethasone palmitate nanoparticles are promising in the treatment of inflammation in rheumatoid arthritis with a very significant difference occurring at the late stage of inflammation allowing to prevent the progression of the disease.
Tiny Dexamethasone palmitate nanoparticles for intravitreal injection: Optimization and in vivo evaluation
Int J Pharm 2021 May 1;600:120509.PMID:33766637DOI:10.1016/j.ijpharm.2021.120509.
Tiny nanoparticles of Dexamethasone palmitate (DXP) were designed as transparent suspensions for intravitreal administration to treat age-related macular degeneration (AMD). The influence of three surfactants (PEG-40-stearate and Pluronic block copolymers F68 and F127) on nanoparticles size and stability was investigated and led to an optimal formulation based on Pluronic F127 stabilizing DXP nanoparticles. Size measurements and TEM revealed tiny nanoparticles (around 35 nm) with a low opacity, compatible with further intravitreal injection. X-Ray powder diffraction (XRPD) and transmission electronic microscopy (TEM) performed on freeze-dried samples showed that DXP nanoparticles were rather monodisperse and amorphous. The efficacy of DXP nanoparticles was assessed in vivo on pigmented rabbits with unilateral intravitreal injections. After breakdown of the blood-retinal barrier (BRB) induced by injection of rhVEGF165 with carrier protein, DXP nanoparticles induced a restoration of the BRB 1 month after their intravitreal injection. However, their efficacy was limited in time most probably by clearance of DXP nanoparticles after 2 months due to their small size.
Dexamethasone palmitate large porous particles: A controlled release formulation for lung delivery of corticosteroids
Eur J Pharm Sci 2018 Feb 15;113:185-192.PMID:28890202DOI:10.1016/j.ejps.2017.09.013.
We have optimized a formulation of a prodrug of dexamethasone (DXM), Dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 μm were produced with a tap density of 0.05g/cm3 and a Fine particle fraction around 40%. The palmitate moiety favors DXP insertion into DPPC bilayers therefore limiting its in vitro release as shown by differential scanning calorimetry. After administering DXP powder intratracheally to rats by insufflation, bronchoalveolar lavage fluid (BALF) and blood samples were collected up to 24h and DXP and DXM concentrations were determined by HPLC analysis after extraction. PK parameters were evaluated according to a non-compartmental model. We observe that DXP remains for up to 6h in the epithelial lining fluid (ELF) of the lungs at very high concentration. In addition, DXP concentration decreases according to two characteristic times. Consequently, DXM can be detected at rather important concentration in ELF up to 24h. The passage of DXP from the lungs to the bloodstream is very poor whereas DXM seems to be absorbed in the blood more easily. These results suggest that once administered DXP undergoes two different processes: hydrolysis into DXM due to the presence of esterases in the lungs and distribution in the lung tissue. This formulation appears promising to reduce systemic exposure and prolong the effect of the drug locally.
Pre-incisional infiltration with ropivacaine plus Dexamethasone palmitate emulsion for postoperative pain in patients undergoing craniotomy: study protocol for a prospective, randomized controlled trial
Trials 2022 Dec 12;23(1):996.PMID:36510271DOI:10.1186/s13063-022-06936-z.
Background: Post-craniotomy pain is a common occurrence which is associated with poor outcomes. Pre-emptive scalp infiltration with dexamethasone and ropivacaine has been proven effective in previous studies but with limited clinical significance. Dexamethasone palmitate emulsion (D-PAL) is a pro-drug incorporating dexamethasone into lipid microspheres with greater anti-inflammatory activity and fewer side effects than free dexamethasone. However, its effects in post-craniotomy pain management remain unknown. This study hypothesizes that pre-emptive scalp infiltration with ropivacaine plus D-PAL emulsion can achieve superior analgesic effects to ropivacaine alone in adult patients undergoing craniotomy. Methods/design: This is a single center, randomized controlled trial enrolling 130 patients scheduled for supratentorial craniotomy, which is expected to last longer than 4 h. We compare the efficacy and safety for postoperative pain relief of ropivacaine plus D-PAL group and ropivacaine alone group following pre-emptive scalp infiltration. Primary outcome will be pain Numerical Rating Scale at 24 h postoperatively. Secondary outcomes will include further analgesia evaluations and drug-related complications within a follow-up period of 3 months. Discussion: This is the first randomized controlled trial aiming to assess the possible benefits or disadvantages of D-PAL emulsion for incisional pain in craniotomy. It may provide an alternative to optimize pain outcome for neurosurgical patients. Trial registration: ClinicalTrials.gov (NCT04488315). Registered on 19 July 2020.
Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions
PLoS One 2014 May 7;9(5):e96252.PMID:24806147DOI:10.1371/journal.pone.0096252.
Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that Dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.