Polysaccharide-based emulsion gels for the prevention of postoperative adhesions and as a drug delivery system using 5-fluorouracil

被引:2
作者
Lee, Jong-Ju [1 ,2 ]
Dinh, Linh [1 ,2 ,3 ]
Kim, Haneul [1 ,2 ]
Lee, Jooyeon [1 ,2 ]
Lee, Juseung [1 ,2 ]
Sung, Yulseung [1 ,2 ]
Yeo, Sooho [1 ,2 ]
Hwang, Sung-Joo [1 ,2 ]
机构
[1] Yonsei Univ, Coll Pharm, 85 Songdogwahak ro, Incheon 21983, South Korea
[2] Yonsei Univ, Yonsei Inst Pharmaceut Sci, 85 Songdogwahak ro, Incheon 21983, South Korea
[3] Univ Cincinnati, James L Winkle Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45229 USA
基金
新加坡国家研究基金会;
关键词
Anti -adhesion agent; Colorectal cancer; Emulsion gel; 5-Fluorouracil; Polysaccharides; XANTHAN GUM; PERITONEAL; COMPLICATIONS; HYDROGEL; RELEASE; PECTIN; ORIGIN; FILMS;
D O I
10.1016/j.ijpharm.2024.124386
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the T-max (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent antiadhesion properties and could be developed as a drug delivery system.
引用
收藏
页数:12
相关论文
共 47 条
[1]   Hydrogel: Preparation, characterization, and applications: A review [J].
Ahmed, Enas M. .
JOURNAL OF ADVANCED RESEARCH, 2015, 6 (02) :105-121
[2]   Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer [J].
Al Sabbagh, Chantal ;
Seguin, Johanne ;
Agapova, Elena ;
Kramerich, Dounia ;
Boudy, Vincent ;
Mignet, Nathalie .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2020, 157 :154-164
[3]  
Alexander A., 2011, Int. J. Appl. Biol. P
[4]   Alginate-pectin microparticles loaded with nanoemulsions as nanocomposites for wound healing [J].
Amante, Chiara ;
Andretto, Valentina ;
Rosso, Annalisa ;
Augusti, Geraldine ;
Marzocco, Stefania ;
Lollo, Giovanna ;
Del Gaudio, Pasquale .
DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 2023, 13 (05) :1343-1357
[5]   Carboxymethyl Cellulose, Pluronic, and Pullulan-Based Compositions Efficiently Enhance Antiadhesion and Tissue Regeneration Properties without Using Any Drug Molecules [J].
An, Jeong Man ;
Shahriar, S. M. Shatil ;
Hasan, Mohammad Nazmul ;
Cho, Sungpil ;
Lee, Yong-Kyu .
ACS APPLIED MATERIALS & INTERFACES, 2021, 13 (14) :15992-16006
[6]   Mucoadhesive drug delivery system: An overview [J].
Boddupalli, Bindu M. ;
Mohammed, Zulkar N. K. ;
Nath, Ravinder A. ;
Banji, David .
JOURNAL OF ADVANCED PHARMACEUTICAL TECHNOLOGY & RESEARCH, 2010, 1 (04) :381-387
[7]   Intra-abdominal Adhesions Definition, Origin, Significance in Surgical Practice, and Treatment Options [J].
Brueggmann, Doerthe ;
Tchartchian, Garri ;
Wallwiener, Markus ;
Muenstedt, Karsten ;
Tinneberg, Hans-Rudolf ;
Hackethal, Andreas .
DEUTSCHES ARZTEBLATT INTERNATIONAL, 2010, 107 (44) :789-U11
[8]   Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions [J].
Burckbuchler, V. ;
Mekhloufi, G. ;
Giteau, A. Paillard ;
Grossiord, J. L. ;
Huille, S. ;
Agnely, F. .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2010, 76 (03) :351-356
[9]   Advancing biomaterials of human origin for tissue engineering [J].
Chen, Fa-Ming ;
Liu, Xiaohua .
PROGRESS IN POLYMER SCIENCE, 2016, 53 :86-168
[10]  
Choi Y., 2021, Master's thesis