Enema based therapy using liposomal formulation of low molecular weight heparin for treatment of active ulcerative colitis: New adjunct therapeutic opportunity

被引:14
作者
Ahmad, Anas [1 ]
Vaghasiya, Kalpesh [1 ]
Kumar, Ajay [1 ]
Alam, Pravej [2 ]
Raza, Syed Shadab [3 ,4 ]
Verma, Rahul Kumar [1 ]
Khan, Rehan [1 ]
机构
[1] Habitat Ctr, Inst Nano Sci & Technol, Phase 10,Sect 64, Mohali 160062, Punjab, India
[2] Prince Sattam Bin Abdulaziz Univ, Coll Sci & Humanities, Dept Biol, POB 173, Alkharj 11942, Saudi Arabia
[3] Eras Lucknow Med Coll & Hosp, Dept Biotechnol, Lab Stem Cell & Restorat Neurol, Lucknow 226003, Uttar Pradesh, India
[4] Era Univ, Dept Stem Cell Biol & Regenerat Med, Lucknow 226003, Uttar Pradesh, India
来源
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2021年 / 121卷
关键词
Ulcerative colitis; Heparin; Liposomes; Inflammation; Drug delivery;
D O I
10.1016/j.msec.2020.111851
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Ulcerative colitis (UC) is an idiopathic bowel disease involving chronic inflammation and ulcers in colon and implicates severe epithelial damage with disruption in colon homeostasis. Presently existing treatments possess serious concerns like off target effects and adverse reactions, drug inactivation, poor absorption and other complications resulting in poor bioavailability. In context of high risk of thrombotic events in UC patients, heparin can offer appreciable benefits in UC management due to its remarkable anti-coagulating properties, its ability to intervene inflammatory pathways and acceleration of wound healing process. However, oral administration of heparin being impractical due to harsh gastric acidic environment and heparin degradation, conventional heparin administration is done via intravenous route. Present study was designed to formulate, characterize and evaluate sustained release heparin formulation in mice model of experimental colitis. Heparin liposomes (HLp) were formulated by solvent evaporation and extrusion process and possessed hydrodynamic diameter of 242 +/- 4.3 nm. Size, shape and surface morphology was confirmed by TEM, SEM and AFM micrographs while encapsulation efficiency and loading of heparin in optimized HLp were 59.61% and 12.27%, respectively. HLp enema administration ameliorated gross disease indices like body weight, colon length, stool consistency, fecal occult blood. Further, anti-inflammatory efficacy of HLp was established in histopathological analysis where HLp appreciably restored protective mucin layer, colon epithelial mucosal histoarchitecture and considerably attenuated mast cell infiltration in colon epithelia. Overall, results of this study indicate that HLp demonstrated an appreciable therapeutic efficacy in experimental colitis and these results are attributed to their ability to suppress inflammation.
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页数:10
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