Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles.
The AAPS journal
2023; 25 (5): 81
mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (- 80 °C) and healthcare professionals to administer the vaccine through the parenteral route has somewhat limited their distribution in rural areas and developing countries. Overcoming these challenges stands to transform future deployment of mRNA vaccines. In this study, we developed an mRNA vaccine that can trigger a systemic immune response through administration via the gastrointestinal (GI) tract and is stable at 4 °C. A library of cationic branched poly(β-amino ester) (PBAE) polymers was synthesized and characterized, from which a polymer with high intracellular mRNA delivery efficiency and immune stimulation capacity was down-selected. mRNA vaccines made with the lead polymer-elicited cellular and humoral immunity in mice. Furthermore, lyophilization conditions of the formulation were optimized to enable storage under refrigeration. Our results suggest that PBAE nanoparticles are potent mRNA delivery platforms that can elicit B cell and T cell activation, including antigen-specific cellular and humoral responses. This system can serve as an easily administrable, potent oral mRNA vaccine.
View details for DOI 10.1208/s12248-023-00844-z
View details for PubMedID 37589795
View details for PubMedCentralID 5768558
- 3D-Printed Microarray Patches for Transdermal Applications JACS AU 2022
Development of oil-based gels as versatile drug delivery systems for pediatric applications
2022; 8 (21): eabm8478
Administering medicines to 0- to 5-year-old children in a resource-limited environment requires dosage forms that circumvent swallowing solids, avoid on-field reconstitution, and are thermostable, cheap, versatile, and taste masking. We present a strategy that stands to solve this multifaceted problem. As many drugs lack adequate water solubility, our formulations used oils, whose textures could be modified with gelling agents to form "oleogels." In a clinical study, we showed that the oleogels can be formulated to be as fluid as thickened beverages and as stiff as yogurt puddings. In swine, oleogels could deliver four drugs ranging three orders of magnitude in their water solubilities and two orders of magnitude in their partition coefficients. Oleogels could be stabilized at 40°C for prolonged durations and used without redispersion. Last, we developed a macrofluidic system enabling fixed and metered dosing. We anticipate that this platform could be adopted for pediatric dosing, palliative care, and gastrointestinal disease applications.
View details for DOI 10.1126/sciadv.abm8478
View details for Web of Science ID 000802745600019
View details for PubMedID 35622910
View details for PubMedCentralID PMC9140966
- Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections MATTER 2022; 5 (3): 975-987
The entry of nanoparticles into solid tumours
2020; 19 (5): 566-+
The concept of nanoparticle transport through gaps between endothelial cells (inter-endothelial gaps) in the tumour blood vessel is a central paradigm in cancer nanomedicine. The size of these gaps was found to be up to 2,000 nm. This justified the development of nanoparticles to treat solid tumours as their size is small enough to extravasate and access the tumour microenvironment. Here we show that these inter-endothelial gaps are not responsible for the transport of nanoparticles into solid tumours. Instead, we found that up to 97% of nanoparticles enter tumours using an active process through endothelial cells. This result is derived from analysis of four different mouse models, three different types of human tumours, mathematical simulation and modelling, and two different types of imaging techniques. These results challenge our current rationale for developing cancer nanomedicine and suggest that understanding these active pathways will unlock strategies to enhance tumour accumulation.
View details for DOI 10.1038/s41563-019-0566-2
View details for Web of Science ID 000508172300001
View details for PubMedID 31932672
Theoretical Approaches to Lentiviral Mediated Neurotrophin Delivery in Potential Treatments of Parkinson's Disease.
The Yale journal of biology and medicine
2016; 89 (2): 215-25
Parkinson's disease is a late-onset neurodegenerative disease, characterized by both motor and non-motor symptoms. Motor symptoms include postural instability, rigidity, and tremor, while non-motor symptoms include anxiety, dementia, and depression. In this integrative review, we discuss PD disease pathophysiology in detail and introduce how neurotrophic growth factor delivery via a retroviral-based system can be used as efficacious tools for targeted gene therapy.
View details for PubMedID 27354847
View details for PubMedCentralID PMC4918865