体内实验证实阴离子 G6.5 树枝状高分子在小鼠体内发生了肠肝转移。
Evidence of oral translocation of anionic G6.5 dendrimers in mice.
机构信息
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, USA.
出版信息
Mol Pharm. 2013 Mar 4;10(3):988-98. doi: 10.1021/mp300436c. Epub 2013 Jan 25.
Abstract
Development of carrier systems to improve oral bioavailability and target drugs to specific sites continues to be an unmet need. The goal of this study was to evaluate the potential of anionic generation (G) 6.5 poly(amido amine) (PAMAM) dendrimers in oral drug delivery by assessing their in vivo oral translocation. G6.5-COOH dendrimers were characterized for their physiochemical characteristics and acute oral toxicity was assessed in CD-1 mice. The dendrimers were labeled with (125)I and their stability evaluated. Oral bioavailability was assessed in the same mouse model. Investigation of the radioactivity profile in plasma revealed presence of both large and small molecular weight compounds. Detailed area under the curve analysis suggests an effective 9.4% bioavailability of radiolabeled marker associated with G6.5-COOH. Results reported here suggest the potential of dendrimers in permeating gastrointestinal barriers in vivo.
摘要
开发载体系统以提高口服生物利用度并将药物靶向特定部位仍然是未满足的需求。本研究的目的是通过评估阴离子生成（G）6.5 聚酰胺-胺（PAMAM）树枝状大分子在口服药物递送中的潜力来评估其体内口服转移的能力。对 G6.5-COOH 树枝状大分子进行了理化性质的表征，并在 CD-1 小鼠中评估了其急性口服毒性。用（125）I 标记树枝状大分子，并评估其稳定性。在相同的小鼠模型中评估了口服生物利用度。对血浆中放射性物质分布的研究表明，存在大分子量和小分子量的化合物。详细的曲线下面积分析表明，与 G6.5-COOH 相关的放射性标记标记物的有效生物利用度为 9.4%。这里报道的结果表明，树枝状大分子具有穿透体内胃肠道屏障的潜力。
相似文献
1
Evidence of oral translocation of anionic G6.5 dendrimers in mice.体内实验证实阴离子 G6.5 树枝状高分子在小鼠体内发生了肠肝转移。
Mol Pharm. 2013 Mar 4;10(3):988-98. doi: 10.1021/mp300436c. Epub 2013 Jan 25.
2
Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin.聚酰胺-胺树枝状聚合物作为喜树碱口服给药的吸收增强剂。
Int J Pharm. 2013 Nov 1;456(1):175-85. doi: 10.1016/j.ijpharm.2013.07.071. Epub 2013 Aug 8.
3
Poly(amido amine) dendrimers in oral delivery.聚（酰胺胺）树枝状大分子在口服给药中的应用。
Tissue Barriers. 2016 Apr 6;4(2):e1173773. doi: 10.1080/21688370.2016.1173773. eCollection 2016 Apr-Jun.
4
Charge affects the oral toxicity of poly(amidoamine) dendrimers.荷电性会影响聚酰胺-胺树枝状高分子的口服毒性。
Eur J Pharm Biopharm. 2013 Jun;84(2):330-4. doi: 10.1016/j.ejpb.2013.01.019. Epub 2013 Feb 16.
5
Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model.第6代羟基聚酰胺-胺树形分子在大型动物脑损伤模型中可提高静脉给药后的中枢神经系统渗透性。
J Control Release. 2017 Mar 10;249:173-182. doi: 10.1016/j.jconrel.2017.01.032. Epub 2017 Jan 27.
6
Structure-skin permeability relationship of dendrimers.树状高分子的结构-皮肤渗透性关系。
Pharm Res. 2011 Sep;28(9):2246-60. doi: 10.1007/s11095-011-0455-0. Epub 2011 Jun 2.
7
Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.PAMAM 树枝状聚合物的跨上皮转运和毒性：对口服药物递送的影响。
Adv Drug Deliv Rev. 2012 May 1;64(6):571-88. doi: 10.1016/j.addr.2011.09.010. Epub 2011 Sep 29.
8
G5-PEG PAMAM dendrimer incorporating nanostructured lipid carriers enhance oral bioavailability and plasma lipid-lowering effect of probucol.聚乙二醇化五倍体树枝状大分子纳米脂质载体提高普罗布考的口服生物利用度和降血脂作用
J Control Release. 2015 Jul 28;210:160-8. doi: 10.1016/j.jconrel.2015.05.281. Epub 2015 May 21.
9
Comparative biodistribution of PAMAM dendrimers and HPMA copolymers in ovarian-tumor-bearing mice.载药树枝状聚合物和聚（N-羟甲基丙烯酰胺）共聚物在荷卵巢癌小鼠体内的比较生物分布。
Biomacromolecules. 2011 Jan 10;12(1):88-96. doi: 10.1021/bm101046d. Epub 2010 Dec 3.
10
The evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: a systematic review and meta-analysis.第4.0代聚（酰胺）胺树枝状大分子作为药物及药物载体的生物医学有效性评估：一项系统综述与荟萃分析
Int J Pharm. 2014 Feb 28;462(1-2):38-43. doi: 10.1016/j.ijpharm.2013.12.033. Epub 2013 Dec 25.
引用本文的文献
1
Anti-biofilm, drug delivery and cytotoxicity properties of dendrimers.树枝状大分子的抗生物膜、药物递送及细胞毒性特性
ADMET DMPK. 2024 Feb 14;12(2):239-267. doi: 10.5599/admet.1917. eCollection 2024.
2
Safety Challenges and Application Strategies for the Use of Dendrimers in Medicine.树枝状大分子在医学应用中的安全挑战与应用策略
Pharmaceutics. 2022 Jun 17;14(6):1292. doi: 10.3390/pharmaceutics14061292.
3
Screening of PI3K-Akt-targeting Drugs for Silkworm against Nucleopolyhedrovirus.筛选针对家蚕核多角体病毒的 PI3K-Akt 靶向药物。
Molecules. 2019 Apr 1;24(7):1260. doi: 10.3390/molecules24071260.
4
Pediatric oral formulation of dendrimer-N-acetyl-l-cysteine conjugates for the treatment of neuroinflammation.用于治疗神经炎症的树枝状聚合物-N-乙酰-L-半胱氨酸缀合物的儿科口服制剂。
Int J Pharm. 2018 Jul 10;545(1-2):113-116. doi: 10.1016/j.ijpharm.2018.04.040. Epub 2018 Apr 20.
5
Toxicology of Engineered Nanoparticles: Focus on Poly(amidoamine) Dendrimers.纳米颗粒的毒理学：以聚酰胺-胺树枝状大分子为例。
Int J Environ Res Public Health. 2018 Feb 14;15(2):338. doi: 10.3390/ijerph15020338.
6
Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers.表面功能会影响经羊膜内递送的树枝状大分子的生物分布和小胶质细胞靶向性。
J Control Release. 2016 Sep 10;237:61-70. doi: 10.1016/j.jconrel.2016.06.046. Epub 2016 Jul 1.
7
Poly(amido amine) dendrimers in oral delivery.聚（酰胺胺）树枝状大分子在口服给药中的应用。
Tissue Barriers. 2016 Apr 6;4(2):e1173773. doi: 10.1080/21688370.2016.1173773. eCollection 2016 Apr-Jun.
8
Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.聚酰胺-胺型树枝状大分子在尤斯灌流小室中跨分离的大鼠空肠黏膜的跨上皮转运
Biomacromolecules. 2014 Aug 11;15(8):2889-95. doi: 10.1021/bm5004465. Epub 2014 Jul 3.
9
Charge affects the oral toxicity of poly(amidoamine) dendrimers.荷电性会影响聚酰胺-胺树枝状高分子的口服毒性。
Eur J Pharm Biopharm. 2013 Jun;84(2):330-4. doi: 10.1016/j.ejpb.2013.01.019. Epub 2013 Feb 16.
本文引用的文献
1
Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.PAMAM 树枝状聚合物的跨上皮转运和毒性：对口服药物递送的影响。
Adv Drug Deliv Rev. 2012 May 1;64(6):571-88. doi: 10.1016/j.addr.2011.09.010. Epub 2011 Sep 29.
2
Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles.粒径和表面电荷显著影响二氧化硅和树枝状纳米粒子的毒性。
Nanotoxicology. 2012 Nov;6(7):713-23. doi: 10.3109/17435390.2011.604442. Epub 2011 Jul 28.
3
Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.壳聚糖-十二烷基硫酸钠纳米粒作为口服胰岛素体内传递的载体系统。
AAPS PharmSciTech. 2011 Sep;12(3):958-64. doi: 10.1208/s12249-011-9647-5. Epub 2011 Jul 15.
4
Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma.头颈部鳞状细胞癌动物模型中的靶向树枝状大分子化疗
J Oral Maxillofac Surg. 2011 Sep;69(9):2452-9. doi: 10.1016/j.joms.2010.12.041.
5
Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening.壳聚糖介导的上皮紧密连接可逆开放的机制及后果。
Biomaterials. 2011 Sep;32(26):6164-73. doi: 10.1016/j.biomaterials.2011.03.056.
6
Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.叶酸靶向纳米颗粒在治疗炎性关节炎方面显示出疗效。
Arthritis Rheum. 2011 Sep;63(9):2671-80. doi: 10.1002/art.30459.
7
Injectable PAMAM dendrimer-PEG hydrogels for the treatment of genital infections: formulation and in vitro and in vivo evaluation.用于治疗生殖器感染的可注射 PAMAM 树枝状大分子-PEG 水凝胶：制剂及体外和体内评价。
Mol Pharm. 2011 Aug 1;8(4):1209-23. doi: 10.1021/mp200027z. Epub 2011 Jun 20.
8
Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.PAMAM 树枝状聚合物跨胎盘转运：在妊娠期间作为药物载体应用的前景。
J Control Release. 2011 Mar 30;150(3):326-38. doi: 10.1016/j.jconrel.2010.11.023. Epub 2010 Dec 1.
9
G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity.G3.5 PAMAM 树枝状聚合物增强了 SN38 的跨上皮转运，同时最大限度地降低了胃肠道毒性。
J Control Release. 2011 Mar 30;150(3):318-25. doi: 10.1016/j.jconrel.2010.11.022. Epub 2010 Nov 27.
10
In vivo efficacy of dendrimer-methylprednisolone conjugate formulation for the treatment of lung inflammation.树枝状聚合物-甲泼尼龙缀合物制剂治疗肺部炎症的体内疗效。
Int J Pharm. 2010 Oct 31;399(1-2):140-7. doi: 10.1016/j.ijpharm.2010.07.030. Epub 2010 Aug 19.
Zotero 插件