Toward Localized Delivery of Biologics for Asthma
Abstract
FY20 PRMRP Topic Area(s): Sustained Release Drug Delivery (Development of technology platform or formulations for sustained-release delivery of drugs for allergy). Respiratory Health (Research on the causes, treatment, and prevention of obstructive pulmonary diseases). Asthma is common in active-duty Service members and civilians. Approximately 10% of patients have severe asthma that is refractory to most therapies, and uncontrolled asthma significantly increases healthcare costs. Biologics, specifically monoclonal antibodies (mAbs), have shown promise in a specific type of severe refractory, which is known as type 2 high asthma. Clinically, these mAbs are administered systemically in high doses, which is associated with the potential for adverse side effects, ranging from acute anaphylaxis to cancer and autoimmune diseases. Therapeutic efficacy of locally delivered mAbs in lungs via inhalation has been previously demonstrated in animal models of asthma. However, due to quick clearance of mAbs from lungs, frequent administration of high doses was required to achieve the therapeutic effects. Also, a significant fraction of the dose gets deactivated due to aerosolization-induced shear stress. Hence, there is an unmet need to develop an inhalable and biocompatible drug delivery platform that can efficiently encapsulate mAbs, maintain their stability during aerosolization process, and exhibit sustained release in asthmatic lungs, thereby reducing clearance. Such a system would achieve high local concentration of the encapsulated biologic, while minimizing systemic adverse effects. Multiple drug delivery systems have been previously developed for inhalation delivery of therapeutics; however, none of them have focused on delivering mAbs for type 2 high asthma. Also, previously developed systems for inhalation drug delivery have one or more major drawbacks. These nanoparticles can overcome the limitations of previously developed platforms for inhalation drug delivery and can encapsulate a wide range of therapeutics with high loading efficiency. Encapsulated agents are released from nanoparticles in a sustained manner due to the slow disassembly of nanoparticles by inflammatory enzymes, which are overexpressed in asthma. Herein, we propose to develop a hydrogel nanoparticle platform for localized delivery of anti-IL5 mAb – a clinically approved mAb for type 2 high asthma. Success of the proposed project will shift the treatment paradigm for type 2 high asthma from systemic to localized, inhalable biologic therapy, thereby impacting the lives of millions of patients. The proposed work would be the first-ever exploration of these novel nanoparticles for inhalation delivery of mAbs to address an unmet clinical need in asthma. Successful accomplishments of the proposed milestones will foster new directions along the entire spectrum of research and clinical care. We will be the first to develop a drug delivery system for localized delivery of mAbs in type 2 high asthma and disseminate this novel hydrogel nanoparticle approach to guide research on other biologics in asthma and other lung diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110048
Entities
People
- Nitin Joshi
Organizations
- United States Army