Polymer-based nanocarriers to transport therapeutic biomacromolecules across the blood-brain barrier

Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases and disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptom...

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Detalles Bibliográficos
Autores: Romero Ben, Elena, Goswami, Upashi, Soto Cruz, Jackeline, Mansoori-Kermani, Amirreza, Mishra, Dhiraj, Martín Saldaña, Sergio, Muñoz Ugartemendia, Jone, Sosnik, Alejandro, Calderón, Marcelo, Beloqui Elizazu, Ana, Larrañaga Espartero, Aitor
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/73102
Acceso en línea:http://hdl.handle.net/10810/73102
Access Level:acceso abierto
Palabra clave:biomacromolecules
blood-brain barrier transport
polymeric nanoparticles
neurological disorders
Descripción
Sumario:Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases and disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptoms of these disorders, therapeutic biomacromolecules can reduce undesired side effects and target specific pathological pathways, thus paving the way towards personalized medicine. However, these biomacromolecules undergo degradation/denaturation processes in the physiological environment and show poor capacity to cross the blood-brain barrier (BBB). Consequently, they rarely reach the central nervous system (CNS) in their active form. Herein, we critically overview several polymeric nanocarriers that can protect and deliver therapeutic biomacromolecules across the BBB. Polymeric nanocarriers are first categorized based on their architecture (biodegradable solid nanoparticles, nanogels, dendrimers, self-assembled nanoparticles) that ultimately determines their physico-chemical properties and function. The available polymeric formulations are then thoroughly analyzed, placing particular attention on those strategies that ensure the stability of the biomacromolecules during their encapsulation process and promote their passage across the BBB by controlling their physical (e.g., mechanical properties, size, surface charge) and chemical (e.g., surface functional groups, targeting motifs) properties. Accordingly, this review gives a unique perspective on polymeric nanocarriers for the delivery of therapeutic biomacromolecules across the BBB, representing a concise, complete and easy-to-follow guide, which will be of high interest for chemists, material scientists, pharmacologists, and biologists. Besides, it also provides a critical perspective about the limited clinical translation of these systems.