Title: Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule Platform for Systemic Non-Invasive Delivery of Oligonucleotide Therapeutics Across the Blood-Brain Barrier to Treat Central Nervous System Disorders Author: AiA Nassar Abstract: Treating central nervous system (CNS) disorders remains a monumental challenge in modern pharmacology due to the highly restrictive and selective nature of the blood-brain barrier (BBB). While advanced molecular therapeutics—such as antisense oligonucleotides (ASOs) and small interfering siRNAs—offer high specificity in silencing disease-causing genes in conditions like Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Spinal Muscular Atrophy (SMA), and Alzheimer's Disease, their high molecular weight, hydrophilic nature, and polyanionic charge prevent passive diffusion across endothelial tight junctions. Currently, clinical interventions rely heavily on invasive intrathecal injections, which present high risks of patient trauma and infections. To overcome these barriers, this study establishes a comprehensive computational (in silico) and microfluidic design framework for a novel Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule (Tf-PLHN) platform. By merging a cationic lipid core (DOTAP) complexed with nucleic acid payloads at an optimized N/P ratio of 4:1 to 6:1, encapsulated within a protective Poly(lactic-co-glycolic acid) (PLGA 50:50) shell, and surface-decorated with 50 to 100 Transferrin ligands, the platform exploits receptor-mediated transcytosis across brain capillary endothelial cells. The computational modeling and physicochemical profiling demonstrate an optimized hydrodynamic diameter of 75–90 nm, a stable negative surface zeta potential (-5 to -12 mV), and an encapsulation efficiency exceeding 85%. Keywords: In Silico Nanomedicine, Blood-Brain Barrier (BBB), Polymeric-Lipid Hybrid Nanocapsules, Transferrin Receptor (TfR), CNS Gene Delivery, Microfluidics.

NASSAR, AIA

DOI: 10.5281/zenodo.24008254
Published: 2026
Container: Not recorded
Publisher: Zenodo
Open access: yes

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BibTeX

@article{allodium:10.5281/zenodo.24008254,
  title = {Title: Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule Platform for Systemic Non-Invasive Delivery of Oligonucleotide Therapeutics Across the Blood-Brain Barrier to Treat Central Nervous System Disorders Author: AiA Nassar Abstract: Treating central nervous system (CNS) disorders remains a monumental challenge in modern pharmacology due to the highly restrictive and selective nature of the blood-brain barrier (BBB). While advanced molecular therapeutics—such as antisense oligonucleotides (ASOs) and small interfering siRNAs—offer high specificity in silencing disease-causing genes in conditions like Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Spinal Muscular Atrophy (SMA), and Alzheimer's Disease, their high molecular weight, hydrophilic nature, and polyanionic charge prevent passive diffusion across endothelial tight junctions. Currently, clinical interventions rely heavily on invasive intrathecal injections, which present high risks of patient trauma and infections. To overcome these barriers, this study establishes a comprehensive computational (in silico) and microfluidic design framework for a novel Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule (Tf-PLHN) platform. By merging a cationic lipid core (DOTAP) complexed with nucleic acid payloads at an optimized N/P ratio of 4:1 to 6:1, encapsulated within a protective Poly(lactic-co-glycolic acid) (PLGA 50:50) shell, and surface-decorated with 50 to 100 Transferrin ligands, the platform exploits receptor-mediated transcytosis across brain capillary endothelial cells. The computational modeling and physicochemical profiling demonstrate an optimized hydrodynamic diameter of 75–90 nm, a stable negative surface zeta potential (-5 to -12 mV), and an encapsulation efficiency exceeding 85\%. Keywords: In Silico Nanomedicine, Blood-Brain Barrier (BBB), Polymeric-Lipid Hybrid Nanocapsules, Transferrin Receptor (TfR), CNS Gene Delivery, Microfluidics.},
  author = {NASSAR, AIA},
  year = {2026},
  doi = {10.5281/zenodo.24008254},
  url = {https://doi.org/10.5281/zenodo.24008254}
}

RIS

TY  - JOUR
TI  - Title: Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule Platform for Systemic Non-Invasive Delivery of Oligonucleotide Therapeutics Across the Blood-Brain Barrier to Treat Central Nervous System Disorders Author: AiA Nassar Abstract: Treating central nervous system (CNS) disorders remains a monumental challenge in modern pharmacology due to the highly restrictive and selective nature of the blood-brain barrier (BBB). While advanced molecular therapeutics—such as antisense oligonucleotides (ASOs) and small interfering siRNAs—offer high specificity in silencing disease-causing genes in conditions like Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Spinal Muscular Atrophy (SMA), and Alzheimer's Disease, their high molecular weight, hydrophilic nature, and polyanionic charge prevent passive diffusion across endothelial tight junctions. Currently, clinical interventions rely heavily on invasive intrathecal injections, which present high risks of patient trauma and infections. To overcome these barriers, this study establishes a comprehensive computational (in silico) and microfluidic design framework for a novel Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule (Tf-PLHN) platform. By merging a cationic lipid core (DOTAP) complexed with nucleic acid payloads at an optimized N/P ratio of 4:1 to 6:1, encapsulated within a protective Poly(lactic-co-glycolic acid) (PLGA 50:50) shell, and surface-decorated with 50 to 100 Transferrin ligands, the platform exploits receptor-mediated transcytosis across brain capillary endothelial cells. The computational modeling and physicochemical profiling demonstrate an optimized hydrodynamic diameter of 75–90 nm, a stable negative surface zeta potential (-5 to -12 mV), and an encapsulation efficiency exceeding 85%. Keywords: In Silico Nanomedicine, Blood-Brain Barrier (BBB), Polymeric-Lipid Hybrid Nanocapsules, Transferrin Receptor (TfR), CNS Gene Delivery, Microfluidics.
AU  - NASSAR, AIA
PY  - 2026
DO  - 10.5281/zenodo.24008254
UR  - https://doi.org/10.5281/zenodo.24008254
ER  -

APA

AIA, N. (2026). Title: Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule Platform for Systemic Non-Invasive Delivery of Oligonucleotide Therapeutics Across the Blood-Brain Barrier to Treat Central Nervous System Disorders Author: AiA Nassar Abstract: Treating central nervous system (CNS) disorders remains a monumental challenge in modern pharmacology due to the highly restrictive and selective nature of the blood-brain barrier (BBB). While advanced molecular therapeutics—such as antisense oligonucleotides (ASOs) and small interfering siRNAs—offer high specificity in silencing disease-causing genes in conditions like Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Spinal Muscular Atrophy (SMA), and Alzheimer's Disease, their high molecular weight, hydrophilic nature, and polyanionic charge prevent passive diffusion across endothelial tight junctions. Currently, clinical interventions rely heavily on invasive intrathecal injections, which present high risks of patient trauma and infections. To overcome these barriers, this study establishes a comprehensive computational (in silico) and microfluidic design framework for a novel Transferrin-Functionalized Polymeric-Lipid Hybrid Nanocapsule (Tf-PLHN) platform. By merging a cationic lipid core (DOTAP) complexed with nucleic acid payloads at an optimized N/P ratio of 4:1 to 6:1, encapsulated within a protective Poly(lactic-co-glycolic acid) (PLGA 50:50) shell, and surface-decorated with 50 to 100 Transferrin ligands, the platform exploits receptor-mediated transcytosis across brain capillary endothelial cells. The computational modeling and physicochemical profiling demonstrate an optimized hydrodynamic diameter of 75–90 nm, a stable negative surface zeta potential (-5 to -12 mV), and an encapsulation efficiency exceeding 85%. Keywords: In Silico Nanomedicine, Blood-Brain Barrier (BBB), Polymeric-Lipid Hybrid Nanocapsules, Transferrin Receptor (TfR), CNS Gene Delivery, Microfluidics.. https://doi.org/10.5281/zenodo.24008254

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datacite · retrieved 2026-11-08T22:19:30.435Z
datacite · retrieved 2026-11-08T22:19:30.435Z