Drug delivery system based on transport characteristics of biological membranes Molecular mechanisms of blood-brain barrier transport system and its contribution to drug delivery to the brain

Tuberculous meningitis (TBM) is an incurable disease with high mortality. It is an extrapulmonary tuberculosis caused by mycobacterium tuberculosis which penetrated the blood-brain barrier and infected the meninges. Mycobacterium tuberculosis lurking in the body mainly reside in macrophages. Anti-tuberculous drugs usually can not target the blood-brain barrier and macrophages, the drug concentration in the lesion is low, which cannot effectively kill mycobacterium tuberculosis, making TBM difficult to treat. Targeted drug delivery systems can target drugs to specific nidus. In the study, we constructed a drug delivery system, which was a cell penetrate peptide B6 and phosphatidylserine (PS) modified polyethylene glycol (PEG) nanomaterial to target the blood-brain barrier and to target macrophages. This nanomaterial was a combined anti-tuberculosis drug delivery system encapsulating antituberculosis drugs rifampicin and pyrazinamide, designed to target macrophages in the brain and kill mycobacterium tuberculosis lurking in the macrophages. We have physically characterized the drug delivery system, and verified the bactericidal ability at cellular and animal level. Results have shown that the targeted drug delivery system had a remarkable efficacy to treat TBM in mice.

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Investigation of Functionalized Poly(N ,N -dimethylacrylamide)-block -polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro

Macromolecular Bioscience ◽

10.1002/mabi.201500172 ◽

2015 ◽

Vol 15 (12) ◽

pp. 1687-1697 ◽

Cited By ~ 14

Author(s):

Maria Gregori ◽

Daniela Bertani ◽

Emanuela Cazzaniga ◽

Antonina Orlando ◽

Michele Mauri ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Brain Barrier ◽

Polystyrene Nanoparticles ◽

Blood Brain ◽

Novel Drug Delivery System ◽

Novel Drug

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Penetration of the blood–brain barrier and the anti-tumour effect of a novel PLGA-lysoGM1/DOX micelle drug delivery system

Nanoscale ◽

10.1039/c9nr08741a ◽

2020 ◽

Vol 12 (5) ◽

pp. 2946-2960 ◽

Cited By ~ 2

Author(s):

Ying Yin ◽

Jun Wang ◽

Meng Yang ◽

Ruolin Du ◽

Giuseppe Pontrelli ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Brain Barrier ◽

Blood Brain ◽

System P ◽

Anti Tumour Effect

a) Diagram depicting the preparation of drug delivery system of PLGA-lysoGM1/DOX micelles. b) Schematic illustration of micelles elicited antitumor. c) Micelles cross BBB via micropinocytosis and autophagy/lysosomal pathways.

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LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00751-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chen He ◽

Zhiyuan Zhang ◽

Yinan Ding ◽

Kangli Xue ◽

Xihui Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Ph Sensitive ◽

Brain Barrier ◽

Blood Brain ◽

Good Ability ◽

Complex Drug

Abstract Background Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood–brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time. Results The Au-DOX@PO-ANG has a good ability to cross the blood–brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume. Conclusion In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

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Innovative approach for nasal drug delivery system for brain target

GSC Advanced Research and Reviews ◽

10.30574/gscarr.2021.9.3.0296 ◽

2021 ◽

Vol 9 (3) ◽

pp. 093-106

Author(s):

Priyadarshani G Patil ◽

Sampada V Marodkar ◽

Sachin J Dighade ◽

Prajakta N Dongare ◽

Bhagyashri A Borade

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Drug Transport ◽

Nasal Delivery ◽

Brain Barrier ◽

Non Invasive ◽

Brain Drug Delivery ◽

Blood Brain

The goal of brain drug targeting technology is the delivery of therapeutics across the blood brain barrier (BBB), including the human BBB. Nose to brain drug delivery has received a great deal of attention as a non- invasive, convenient and reliable drug delivery system. For the systemic and targetedadministration of drug. The various drug deliveries through some drug transport pathways, Factor influencing nasal drug absorption, formulation strategies nose to brain, colloidal carriers in nose to brain drug delivery system and nasal delivery systems. Physiological barriers (BBB) that restricts the delivery of drug to CNS. Thus intranasal route has attracted a wide attention of convenient, non-invasive, reliable, and safe route to achieve faster and higher level of drug in the brain through olfactory region by passing blood brain barrier. Intranasal administration rapid onset of action, no first –pass effect , no gastrointestinal degradation lungs toxicity and non-invasiveness application and also improves bioavailability.

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LRP1-mediated pH-sensitive Polymersomes Facilitate Combination Therapy of Glioblastoma in Vitro and in Vivo

10.21203/rs.3.rs-80586/v1 ◽

2020 ◽

Author(s):

Chen He ◽

Zhiyuan Zhang ◽

Yinan Ding ◽

Kangli Xue ◽

Xihui Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Ph Sensitive ◽

Brain Barrier ◽

Blood Brain ◽

Good Ability ◽

Complex Drug

Abstract Background: Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood-brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and signiﬁcantly increased survival time.Results: The Au-DOX@PO-ANG has a good ability to cross the blood-brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume.Conclusion: In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

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Rapid and efficient crossing blood-brain barrier: Hydrophobic drug delivery system based on propionylated amylose helix nanoclusters

Biomaterials ◽

10.1016/j.biomaterials.2016.10.045 ◽

2017 ◽

Vol 113 ◽

pp. 133-144 ◽

Cited By ~ 14

Author(s):

Wei Gao ◽

Yongchun Liu ◽

Guixia Jing ◽

Ke Li ◽

Yuan Zhao ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Brain Barrier ◽

Hydrophobic Drug ◽

Blood Brain

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Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00925-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chiun-Wei Huang ◽

Chia-Pao Chuang ◽

Yan-Jun Chen ◽

Hsu-Yuan Wang ◽

Jia-Jia Lin ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Delivery System ◽

Tumor Targeting ◽

Brain Barrier ◽

Iron Storage ◽

Blood Brain ◽

Delivery Technique ◽

Orthotopic Glioma

Abstract Background Ferritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood–brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system. Results In this study, a unique integrin α2β1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2β1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days. Conclusions We believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine. Graphic Abstract

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