Review
Pharmacology & Pharmacy
Bhakti Pawar, Nupur Vasdev, Tanisha Gupta, Mahi Mhatre, Anand More, Neelima Anup, Rakesh Kumar Tekade
Summary: This article discusses the limitations of the blood-brain barrier (BBB) on brain drug delivery and ways to overcome it using new techniques such as nanomedicine, nose-to-brain drug delivery, and peptides as drug delivery carriers. It also helps to understand the factors affecting BBB permeability and the body clearance of drugs delivered to the brain.
Article
Pharmacology & Pharmacy
Julia Georgieva, Moriah Katt, Zhou Ye, Benjamin J. Umlauf, Cody J. Wenthur, Eric Shusta
Summary: The restrictive nature of the brain vasculature limits the exposure of central nervous system (CNS) to blood-borne biotherapeutics. The use of receptor-mediated transcytosis (RMT) mechanisms in blood-brain barrier endothelial cells can increase the bioavailability of such therapeutics. The antibody 46.1 has been identified to accumulate in the mouse brain and can deliver drug cargo to the CNS, primarily through the cavernous sinus-arterial route.
Review
Pharmacology & Pharmacy
Eun Seo Choi, Eric Shusta
Summary: The review focuses on known and emerging RMT systems, targeting antibody properties related to BBB trafficking, and antibody validation strategies. Clinical development of known RMT targeting systems and identifying novel BBB RMT targets are important strategies for treating CNS diseases. Expanding the identification of BBB RMT systems and targeting molecule engineering will greatly contribute to the treatment of neurological diseases.
EXPERT OPINION ON DRUG DELIVERY
(2023)
Article
Chemistry, Multidisciplinary
Jun-Yong Wu, Yong-Jiang Li, Xiong-Bin Hu, Si Huang, Shilin Luo, Tiantian Tang, Da-Xiong Xiang
Summary: The study compared Exos and BNVs for brain tumor drug delivery, finding that BNVs derived from brain-derived endothelial cells are a promising alternative with higher yield and similar drug-loading capacity to natural exosomes. Despite different mechanisms, BNV/DOX showed similar therapeutic effects to Exo/DOX in inhibiting the progression of glioblastoma, with minimal systemic toxicity. The findings suggest that autologous BNVs are an effective alternative to Exos for brain tumor nanomedicine.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Medicine, Research & Experimental
Michelle A. Erickson, William A. Banks
Summary: Disruption of the blood-brain barrier (BBB) can occur through different mechanisms and pathways, resulting in different neurological insults. The importance of transcellular pathways in BBB disruption has been highlighted. Transcytotic mechanisms are less clearly linked to permeability compared to membrane spanning canaliculi and fenestrations. Cellular components involved in transcellular mechanisms of BBB disruption are being discovered and measured, adding to our classic knowledge based on ultrastructural studies.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Jun-Yong Wu, Yong-Jiang Li, Jiemin Wang, Xiong-Bin Hu, Si Huang, Shilin Luo, Da-Xiong Xiang
Summary: The multifunctional DTX@Ang-EM significantly inhibit the growth of orthotopic GBM with reduced side effects of chemotherapy, providing a new strategy for targeted brain drug delivery and GBM therapy.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Ke Sun, Xue Zheng, Hongzhen Jin, Fan Yu, Wei Zhao
Summary: Central nervous system diseases pose a threat to global health, but developing drugs targeting the CNS is challenging due to the unique characteristics of the brain and spinal cord. Exosomes, as CNS drug delivery tools, stand out for their low immunogenicity, ability to cross the blood-brain barrier, and flexibility in drug encapsulation. Research over the past decade has shown the potential of exosomes in CNS drug delivery, and there are still challenges and prospects to be addressed.
Article
Pharmacology & Pharmacy
Barbara Sanchez-Dengra, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez
Summary: The blood-brain barrier restricts the access of substances to the central nervous system, hindering the treatment of brain and spinal cord pathologies. This study analyzes and comments on various strategies, both invasive and non-invasive, to enhance substance access to the central nervous system. Invasive techniques include direct injection and therapeutic opening of the blood-brain barrier, while non-invasive techniques involve alternative administration routes, inhibition of efflux transporters, chemical modification of molecules, and the use of nanocarriers. The combination of different strategies may be the most promising approach to increase substance access to the central nervous system.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Review
Biochemistry & Molecular Biology
V. Manimaran, R. P. Nivetha, T. Tamilanban, J. Narayanan, Subramaniyan Vetriselvan, Neeraj Kumar Fuloria, Suresh V. Chinni, Mahendran Sekar, Shivkanya Fuloria, Ling Shing Wong, Anupam Biswas, Gobinath Ramachawolran, Siddharthan Selvaraj
Summary: Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. They effectively address the limitations of conventional drug therapy and are considered an innovative drug delivery system. This article covers topics such as the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties, nanogel classification, synthesis, drug release mechanisms, and various biological applications.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Pharmacology & Pharmacy
Hojun Choi, Kyungsun Choi, Dae-Hwan Kim, Byung-Koo Oh, Hwayoung Yim, Soojin Jo, Chulhee Choi
Summary: Delivering therapeutics to the central nervous system (CNS) is difficult due to the blood-brain barrier (BBB). Different mechanisms, such as receptor-mediated transcytosis, can be utilized for therapeutic delivery across the BBB. Exosomes, as natural nanoparticles, have the potential to cross the BBB and can be surface-engineered. Surface-modified exosomes have shown enhanced CNS delivery in preclinical studies, but the development of clinically approved exosome therapeutics for CNS diseases requires addressing the challenges of monitoring exosomal delivery to the brain parenchyma in vivo and understanding the mechanisms of BBB crossing.
Review
Pharmacology & Pharmacy
Liang Han
Summary: The blood-brain barrier tightly regulates substance transport into and out of the brain, but strategies to modulate the BBB have the potential to improve drug delivery and therapeutic efficacy against brain diseases. Various modulation strategies have been investigated, showing promising directions for future research.
Article
Biochemistry & Molecular Biology
Nivetha Krishna Moorthy, Oliver Seifert, Stephan Eisler, Sara Weirich, Roland E. Kontermann, Markus Rehm, Gavin Fullstone
Summary: The study investigated the effectiveness of antibody-based fusion proteins combining hexavalent TRAIL and ANG2 for GBM treatment, demonstrating potent induction of apoptosis. However, low TRAIL receptor expression on the blood-brain barrier endothelial cells interfered with efficient transport of the fusion proteins. Therapeutic strategies may need to include combinatorial approaches, such as TRAIL-R masking, to achieve effective CNS transport.
Review
Medicine, Research & Experimental
Sofia Parrasia, Ildiko Szabo, Mario Zoratti, Lucia Biasutto
Summary: Central nervous system diseases are difficult to treat due to the blood-brain barrier (BBB), which prevents most drugs from reaching the brain. Peptides show promise in helping drugs cross the BBB and target the brain. However, there are challenges such as potential toxic effects, short in vivo lifespan, and inadequate drug levels in the brain.
MOLECULAR PHARMACEUTICS
(2022)
Review
Cell & Tissue Engineering
Olivia Rice, Allison Surian, Yupeng Chen
Summary: The blood-brain barrier is a specialized biological barrier that protects the brain from invasion. In vitro modeling of the blood-brain barrier has provided insights into transport mechanisms and disease effects, aiding in the development of treatments.
JOURNAL OF TISSUE ENGINEERING
(2022)
Article
Behavioral Sciences
Raghuram Kandimalla, Mohd Saeed, Neetu Tyagi, Ramesh C. Gupta, Farrukh Aqil
Summary: Alzheimer's disease (AD) is a widely studied neurological disorder that affects millions of individuals worldwide and is caused by misfolded proteins in the brain, particularly amyloid-beta and tau. While therapeutic interventions and nanotechnological advancements can help manage AD symptoms, a cure for this disease has yet to be found. Exosomes, which can originate from various cell and tissue types, have a dual role in the progression and treatment of AD. They can be manipulated to deliver therapeutic cargos, both small molecules and macromolecules, to the brain. This review focuses on the roles of exosomes in the pathology, diagnosis, and treatment of AD, as well as their potential as drug carriers for AD treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Greta Camilla Magnano, Marika Quadri, Elisabetta Palazzo, Roberta Lotti, Francesca Loschi, Stefano Dall'Acqua, Michela Abrami, Francesca Larese Filon, Alessandra Marconi, Dritan Hasa
Summary: This study aimed to investigate the loading of sildenafil citrate in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with permeability experiments using porcine skin. The results showed that the results obtained using the 3D skin equivalent were comparable to those obtained using porcine skin, suggesting that the 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2024)
Article
Pharmacology & Pharmacy
James W. Mckeage, Andrew Z. H. Tan, Andrew J. Taberner
Summary: Needle-free jet injection is a promising alternative drug delivery technique that offers rapid, non-invasive, and large-volume injections. The study presents a prototype multi-orifice nozzle and a computational fluid dynamic model to demonstrate the feasibility and effectiveness of this technology.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2024)