Hydroxypropyl-beta-cyclodextrin is an ether derivative generated by the reaction of beta-Cyclodextrin with epichlorohydrin[1]. Hydroxypropyl-beta-cyclodextrin can form water-soluble complexes by encapsulating poorly soluble drug molecules in hydrophobic cavity, significantly enhancing the solubility and bioavailability of the drugs. Hydroxypropyl-beta-cyclodextrin can also be used as a pharmaceutical excipient in oral, injectable, and mucosal drug delivery systems[2]. Hydroxypropyl-beta-cyclodextrin can bind and dissolve cholesterol crystals within cells, promote cholesterol efflux and metabolism, and enhance lysosomal function and autophagic clearance by activating transcription factor EB[3]. Hydroxypropyl-beta-cyclodextrin can disrupt cholesterol homeostasis, inducing G2/M cell cycle arrest and apoptosis in leukemia cells, and systemic administration has been shown to be safe[4].
In vitro, after pre-treatment of bone marrow-derived macrophages (BMDMs) with Hydroxypropyl-beta-cyclodextrin (1.95mM) for 4 hours, followed by stimulation with lipopolysaccharide (LPS; 100ng/ml) for 4 hours, Hydroxypropyl-beta-cyclodextrin significantly increased the protein secretion of the pro-inflammatory cytokine TNF-α, upregulated the expression of pro-inflammatory genes, and downregulated the expression of anti-inflammatory genes[5]. Hydroxypropyl-beta-cyclodextrin (2.5–20mM) pre-treatment of Vero E6 cells and Calu-3 lung epithelial cells for 1 hour, followed by infection with SARS-CoV-2 (MOI = 0.1–0.5) for 24–72 hours, significantly inhibited viral replication and reduced virus-induced inflammation[6].
In vivo, Hydroxypropyl-beta-cyclodextrin (4000mg/kg; intraperitoneal injection twice a week) was used to treat Tg19959 Alzheimer's disease model mice for 4 months. Hydroxypropyl-beta-cyclodextrin significantly improved the learning and memory functions of the mice, reduced amyloid-beta (Aβ) plaque deposition, and attenuated tau pathology in the brain[7]. Hydroxypropyl-beta-cyclodextrin (10% w/v) was used as a drug carrier and administered intravenously three times a week (at a dose of 2.5–20mg/kg) to NOD/SCID mice that had been inoculated with SU-DHL-6 tumor cells. Hydroxypropyl-beta-cyclodextrin significantly increased the water solubility of Purinostat Mesylate (PM), enhanced its anti-tumor efficacy, and improved its pharmacokinetic properties[8].
References:
[1] Gould S, Scott RC. 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): a toxicology review. Food Chem Toxicol. 2005 Oct;43(10):1451-9.
[2] Li J, Li Y, Su W, et al. In vivo anti-obesity efficacy of fucoxanthin/HP-β-CD nanofibers in high-fat diet induced obese mice. Food Chem. 2023 Dec 15;429:136790.
[3] Castiblanco D, Rudd-Schmidt JA, Noori T, et al. Severely impaired CTL killing is a feature of the neurological disorder Niemann-Pick disease type C1. Blood. 2022 Mar 24;139(12):1833-1849.
[4] Yokoo M, Kubota Y, Motoyama K, et al. 2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent. PLoS One. 2015 Nov 4;10(11):e0141946.
[5] Houben T, Yadati T, de Kruijf R, et al. Pro-Inflammatory Implications of 2-Hydroxypropyl-β-cyclodextrin Treatment. Front Immunol. 2021 Aug 20;12:716357.
[6] Bezerra BB, Silva GPDD, Coelho SVA, et al. Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines. Antiviral Res. 2022 Sep;205:105373.
[7] Yao J, Ho D, Calingasan NY, et al. Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease. J Exp Med. 2012 Dec 17;209(13):2501-13.
[8] Zhu Z, Wen J, Xu Y, et al. Therapeutic efficacy of an injectable formulation of purinostat mesylate in SU-DHL-6 tumour model. Ann Med. 2022 Dec;54(1):743-753.
Hydroxypropyl-beta-cyclodextrin一种由beta-Cyclodextrin与环氧丙烷反应生成的醚化衍生物[1]，可通过疏水空腔包合难溶性药物分子，形成水溶性复合物，显著提高药物的溶解度和生物利用度，并可作为药物赋形剂用于口服、注射和黏膜给药系统[2]。Hydroxypropyl-beta-cyclodextrin够结合并溶解细胞内的胆固醇晶体，促进胆固醇外流和代谢，并通过激活转录因子EB增强溶酶体功能和自噬清除能力[3]。Hydroxypropyl-beta-cyclodextrin通过扰乱胆固醇稳态，诱导白血病细胞G2/M期周期阻滞和凋亡，且系统性给药具有安全性[4]。
在体外，Hydroxypropyl-beta-cyclodextrin（1.95mM）预处理骨髓来源的巨噬细胞（BMDMs）4小时后，随后以脂多糖（LPS，100ng/ml）刺激4h，Hydroxypropyl-beta-cyclodextrin显著增加促炎因子TNF-α的蛋白分泌，同时升高促炎基因的表达水平，降低抗炎基因的表达水平[5]。Hydroxypropyl-beta-cyclodextrin（2.5–20mM）预处理Vero E6细胞和Calu-3肺上皮细胞1小时，随后以SARS-CoV-2（MOI=0.1–0.5）感染24–72小时，Hydroxypropyl-beta-cyclodextrin显著抑制病毒复制，同时降低病毒诱导的炎症反[6]。
在体内，Hydroxypropyl-beta-cyclodextrin（4000mg/kg；每周两次腹腔注射），用于处理Tg19959阿尔茨海默病模型小鼠，持续4个月，显著改善了小鼠的学习和记忆功能，同时减少了脑内Aβ斑块沉积和tau病理[7]。Hydroxypropyl-beta-cyclodextrin（10% w/v）作为药物载体，通过每周三次静脉注射（剂量为2.5–20mg/kg），用于处理已接种SU-DHL-6肿瘤细胞的NOD/SCID小鼠。Hydroxypropyl-beta-cyclodextrin显著提高了Purinostat Mesylate（PM）的水溶性，增强了其抗肿瘤疗效，并改善了药代动力学特性[8]。