Abstract
Drug delivery through the Blood–Brain Barrier (BBB) represents a significant challenge. Despite the current strategies to circumvent the BBB, nanotechnology offers unprecedented opportunities for combining selective delivery, improved bioavailability, drug protection, and enhanced pharmacokinetics profiles. Chitosan nanocarriers allow for a more efficacious strategy at the cellular and sub-cellular levels. Boron Neutron Capture Therapy (BNCT) is a targeted chemo-radiotherapeutic technique that allows the selective depletion of cancer cells by means of selective tagging of cancer cells with 10B, followed by irradiation with low-energy neutrons. Consequently, the combination of a polymer-based nanodelivery system enclosing an effective BNCT pharmacophore can potentially lead to the selective delivery of the load to cancer cells beyond the BBB. In this work, synthesized novel boronated agents based on carborane-functionalized Delocalized Lipophilic Cations (DLCs) are assessed for safety and selective targeting of tumour cells. The compounds are then encapsulated in nanocarriers constituted by chitosan to promote permeability through the BBB. Additionally, chitosan was used in combination with polypyrrole to form a smart composite nanocapsule, which is expected to release its drug load with variations in pH. Results indicate the achievement of more selective boron delivery to cells via carboranyl DLCs. Finally, preliminary cell studies indicate no toxicity was detected in chitosan nanocapsules, further enhancing its viability as a potential delivery vehicle in the BNCT of brain tumours.
Highlights
The brain is the most complex and powerful organ in the human body
For materials used in the formulation of the nanosystems: chitosan (LMW), pyrrole, aqueous acetic acid, sodium tri-polyphosphate, monobasic sodium phosphate, and dibasic sodium phosphate were all purchased from Sigma Aldrich, UK
The copolymerisation of chitosan with polypyrrole was introduced in this study; polypyrrole has been shown to have favourable characteristics in terms of safety, stability, high conductivity, and pH-responsive activity releasing the drug at more tumour specific regions [42]
Summary
The brain is the most complex and powerful organ in the human body. The human brain represents about 2% of the total body weight; it uses the same amount of energy as all the body’s skeletal muscles when at rest [2]. Due to the importance of the brain, the body formed a system to protect this organ from damage that can be caused by potentially dangerous toxins. The BBB presents three types of junctions, as described by Stamatovic et al [7]. These are adherent junctions, tight junctions (TJs), and gap junctions. These barriers allow for restricted access of drugs to the brain. Larger molecules require a specialised transport system in order to permeate the BBB
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