Evolving new-age strategies to transport therapeutics across the blood-brain-barrier

被引:55
作者
Choudhari, Manisha [1 ]
Hejmady, Siddhanth [1 ]
Saha, Ranendra Narayan [2 ]
Damle, Shantanu [3 ]
Singhvi, Gautam [1 ]
Alexander, Amit [4 ]
Kesharwani, Prashant [5 ]
Dubey, Sunil Kumar [1 ,6 ]
机构
[1] Birla Inst Technol & Sci, Dept Pharm, Pilani Campus, Pilani 333031, Rajasthan, India
[2] Birla Inst Technol & Sci, Dubai Campus, Pilani, U Arab Emirates
[3] Colorcon Asia Pvt Ltd, Verna Ind Estate, Verna 403722, Goa, India
[4] Govt India, Natl Inst Pharmaceut Educ & Res NIPER GUWAHATI, Dept Pharmaceut Technol Formulat, Minist Chem & Fertilizers,Dept Pharmaceut, Gauhati 781101, Assam, India
[5] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut, New Delhi 110062, India
[6] Emami Ltd, R&D Healthcare Div, 13 BT Rd, Kolkata 700056, India
关键词
Blood-brain barrier; Cerebrospinal fluid; Peptide-based vector; Molecular trojan horse; Monoclonal antibody; Human insulin receptor; CENTRAL-NERVOUS-SYSTEM; CARRIER-MEDIATED TRANSPORT; PEPTIDE-BASED VECTORS; DRUG-DELIVERY; IN-VIVO; TRANSFERRIN RECEPTOR; FUSION PROTEIN; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; ION TRANSPORTERS;
D O I
10.1016/j.ijpharm.2021.120351
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in targeting drugs specific to the brain. Neoplasm compromising the internal structure of BBB that results in impaired vasculature is called as blood tumor barrier (BTB). Besides, the BBB serves as a chief hindrance to the passage of a drug into the brain parenchyma. The small and hydrophilic drugs majorly display an absence of desired molecular characteristics required to cross the BBB. Furthermore, all classes of biologics have failed in the clinical trials of brain diseases over the past years since these biologics are large molecules that do not cross the BBB. Also, new strategies have been discovered that use the Trojan horse technology with the re-engineered biologics for BBB transport. Thus, this review delivers information about the different grades of tumors (I-IV) i.e. examples of BBB/BTB heterogenicity along with the different mechanisms for transporting the therapeutics into the brain tumors by crossing BBB. This review also provides insights into the emerging approaches of peptide delivery and the non-invasive and brain-specific molecular Trojan horse targeting technologies. Also, the several challenges in the clinical development of BBB penetrating IgG fusion protein have been discussed.
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页数:19
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