scholarly journals A Nanogel with Effective Blood-Brain Barrier Penetration Ability through Passive and Active Dual-Targeting Function

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jun Liu ◽  
Meng Li ◽  
Yong Huang ◽  
Li Zhang ◽  
Wei Li ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Particle Surface ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Drug Accumulation ◽  
Brain Barrier ◽  
Temperature Sensitive ◽  
Passive Targeting ◽  
Blood Brain ◽  
Penetration Ability

Clinically, surgery assisted by chemotherapy is the most effective treatment of cancer. But from our clinical observation, the median survival of patients with glioblastoma is still not so good with only 15-16 months. The low therapeutic index is mainly due to the blood-brain barrier (BBB) which significantly hindered the chemotherapeutic drug accumulation in tumor tissue. One main composition of the BBB is astrocyte, which contains a lipophilic cell membrane, which prevents more than 98% of small-molecule drugs from entering the brain. Previously, we found that the nanogel with passive targeting function can increase the BBB penetration ability, which indicates that it could be used to overcome the above mentioned in vivo obstacles which promoted drug accumulation in the tumor. In this study, thermosensitive targeted nanogel delivery systems (DPPC) with cell-penetrating peptides (CPP) are introduced onto the particle surface for active astrocyte breaking. The hydrodynamic radius of DPPC is around 300 nm, the potential is about 0-5 mV, and the TEM and DLS studies further confirm its well spherical morphology and uniform distribution. The DPPC is verified as the biocompatible carriers for further application by cell viability tests. The in vitro-constructed BBB model successfully proves that DPPC can efficiently penetrate the BBB, which is attributed to both the temperature-sensitive passive targeting and the active CPP penetration. Consequently, the intracellular doxorubicin (DOX) promotes such functional DPPC at the relatively high temperature inside tumor microenvironment (TME) (~42°C), which obviously improves intratumor drug accumulation and tumor cell-killing effects. The dual-targeted nanogel delivery systems designed in this study provides a more effective strategy for the treatment of glioma.

scholarly journals Dendrimeric Poly(Epsilon-Lysine) Delivery Systems for the Enhanced Permeability of Flurbiprofen across the Blood-Brain Barrier in Alzheimer’s Disease

2018 ◽  
Vol 19 (10) ◽  
pp. 3224 ◽  
Author(s):  
Shafq Al-azzawi ◽  
Dhafir Masheta ◽  
Anna Guildford ◽  
Gary Phillips ◽  
Matteo Santin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Solid Phase ◽  
Synthesis Method ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Target Cells ◽  
Target Tissue ◽  
Blood Brain

Alzheimer’s disease (AD) is a progressive brain disorder and age-related disease characterised by abnormal accumulation of β-amyloid (Aβ). The development of drugs to combat AD is hampered by the lack of therapeutically-active molecules able to cross the blood-brain barrier (BBB). It is agreed that specifically-designed carriers, such as dendrimers, could support the drug penetration across the BBB. The aim of this study was to design biocompatible and biodegradable dendrimeric delivery systems able to carry Flurbiprofen (FP), as drug for AD treatment, across the BBB and liberate it at the target tissue. These dendrons were synthesised using solid-phase peptide synthesis method and characterised by mass spectrometry and fourier-transform infrared spectroscopy (FTIR). The results revealed successful synthesis of dendrons having FP been integrated during the synthesis at their branching ends. Cytotoxicity assays demonstrated the biocompatibility of the delivery systems, whereas HPLC analysis showed high percentages of permeability across an in vitro BBB model for FP-integrated dendrons. Results also revealed the efficiency of drug conjugates on the γ-secretase enzyme in target cells with evidence of eventual drug release by hydrolysis of the carrier. This study demonstrates that the coupling of FP to dendrimeric delivery systems can successfully be achieved during the synthesis of the poly(epsilon-lysine) macromolecules to improve the transport of the active drug across the BBB.

Efficiency of lipid-based nano drug delivery systems in crossing the blood-brain barrier: a review

2021 ◽  
pp. 118278
Author(s):  
Maliheh Dayani ◽  
Salar Khaledian ◽  
Arad Fatahian ◽  
Reza Fatahian ◽  
Fleming Martinez
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Blood Brain ◽  
Nano Drug Delivery

Gemini quaternary ammonium-incorporated biodegradable multiblock polyurethane micelles for brain drug delivery

RSC Advances ◽  
2015 ◽  
Vol 5 (8) ◽  
pp. 6160-6171 ◽  
Author(s):  
Rui-Chao Liang ◽  
Fang Fang ◽  
Yan-Chao Wang ◽  
Ni-Jia Song ◽  
Jie-Hua Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Quaternary Ammonium ◽  
Drug Accumulation ◽  
Brain Barrier ◽  
Brain Drug Delivery ◽  
Blood Brain

Gemini quaternary ammonium (GQA) incorporated biodegradable multiblock polyurethane (BMPUs) micelles could transport drug across blood–brain barrier and improve brain drug accumulation.

scholarly journals Combination of cell-penetrating peptides with nanomaterials for the potential therapeutics of central nervous system disorders: a review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zhang ◽  
Pan Guo ◽  
Zhe Ma ◽  
Peng Lu ◽  
Dereje Kebebe ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Human Life ◽  
Scientific Basis ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Diseases ◽  
Blood Brain ◽  
Cell Penetrating

AbstractAlthough nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood–brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood–brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases

2020 ◽  
Vol 17 (5) ◽  
pp. 375-386 ◽  
Author(s):  
Behrang Shiri Varnamkhasti ◽  
Samira Jafari ◽  
Fereshteh Taghavi ◽  
Loghman Alaei ◽  
Zhila Izadi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Disorders ◽  
Blood Brain ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
The Central Nervous System ◽  
Low Cytotoxicity ◽  
The Brain

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.

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