Biology subjects

Yu, Y.-S.

Publications and source records attributed to Yu, Y.-S..

3 recordsLinked to original sources

bioRxiv2023

Feasibility of intranasal delivery of thin-film freeze-dried monoclonal antibodies

Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-drying can be applied to prepare aerosolizable mAb dry powders and that the dry powders can be sprayed into the posterior nasal cavity using Aptar Pharmas Unidose (UDS) Powder Nasal Spray System. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared AUG-3387 thin-film freeze-dried powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C powder) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder device. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder device were studied using 3D-printed nasal replica casts based on an adult model and a child model. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spray the powder using the UDS Powder device.

pharmacology and toxicology↗

bioRxiv2022

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive AS01B-adjuvanted vaccine powders

Intranasal vaccination by directly applying a vaccine dry powder is appealing. However, a method that can be used to transform a vaccine from a liquid to a dry powder and a device that can be used to administer the powder to the desired region(s) of the nasal cavity are critical for a successful intranasal vaccination. In the present study, using a model vaccine that contains the liposomal AS01B as an adjuvant and ovalbumin (OVA) as a model antigen, it was shown that thin-film freeze-drying can be applied to convert the liquid vaccine containing sucrose at a sucrose to lipid ratio of 15:1 (w/w), in the presence or absence of carboxymethyl cellulose sodium salt (CMC) as a mucoadhesive agent, into dry powders. Ultimately, the thin-film freeze-dried AS01B/OVA vaccine powder containing 1.9% w/w of CMC (i.e., TFF AS01B/OVA/CMC1.9% powder) was selected for additional evaluation because the TFF AS01B/OVA/CMC1.9% powder was mucoadhesive and maintained the integrity of the antigen and the physical properties of the vaccine. Compared to the TFF AS01B/OVA powder that did not contain CMC, the TFF AS01B/OVA/CMC1.9% powder had a lower moisture content and a higher glass transition temperature and was more porous. In addition, the TFF AS01B/OVA/CMC1.9% thin films were relatively thicker than the TFF AS01B/OVA thin films without CMC. When sprayed with the Unit Dose System Powder (UDSP) nasal device, the TFF AS01B/OVA powder and the TFF AS01B/OVA/CMC1.9% powder generated similar particle size distribution curves, spray patterns, and plume geometries. Importantly, after the TFF AS01B/OVA/CMC1.9% powder was sprayed with the UDSP nasal device, the integrity of the OVA antigen and the AS01B liposomal adjuvant did not change. Finally, a Taguchi L8 orthogonal array was applied to identify the optimal parameters for using the UDSP device to deliver the TFF AS01B/OVA/CMC1.9% vaccine powder to the middle and lower turbinate and the nasopharynx regions in both adult and child nasal casts. Results from this study showed that it is feasible to apply the TFF technology to transform a nasal vaccine candidate from liquid to a dry powder and then use the UDSP nasal device to deliver the TFF vaccine powder to the desired regions in the nasal cavity for intranasal vaccination.

pharmacology and toxicology↗

bioRxiv2022

Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential

Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the safety concerns and limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have potential to obviate these shortcomings. In this study, we improved a previously developed modified piggyBac system with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3 terminal repeat domain of hyperactive piggyBac (hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressing Quantum PBase v2 to generate an optimal piggyBac system, Quantum pBac (qPB), for use in T cells. Cells transfected with qPB expressing CD20/CD19 CAR outperformed those transfected with the same donor vector and plasmid expressing hyPB transposase in terms of CAR-T cell production. Importantly, qPB yielded mainly CD8+ CAR-TSCM cells, and the qPB- induced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells both in vitro and in vivo. Our findings confirm qPB as a promising virus-free vector system with a payload capacity to incorporate multiple genes. This system is highly efficient and potentially safe for mediating transgene integration.

cancer biology↗