Basanth Babu Eedara is currently a Research Assistant Professor in Prof. Heidi M. Mansour’s lab at the Florida International University (FIU) Center for Translational Science in Port Saint Lucie, Florida. As a former Postdoctoral Research Associate (Jul 2020-Feb 2022 at The University of Arizona, Tucson) and current Research Assistant Professor at FIU in Prof. Mansour’s lab, his research focuses on the development and evaluation (i.e., physicochemical, and biological) of novel inhalable drug formulations for treating lung conditions.

Dr. Eedara completed his PhD in the Pharmaceutical Sciences under the supervision of Dr. Shyamal C. Das and Prof. Ian G. Tucker at the University of Otago in Dunedin, New Zealand. Prior to this, he worked as an Assistant Professor (Feb 2012- Dec 2014) in the Department of Pharmaceutics at St. Peter’s Institute of Pharmaceutical Sciences, Telangana, India. His long-term career goals involve becoming an independent researcher and developing formulations to deliver drugs in a targeted manner to prolong and localize in the lungs. He is also interested in understanding the dissolution behavior of respirable size particles which can be useful to establish differences between formulations and to estimate the dissolution behavior in the lungs. Techniques used for development and evaluation of inhalable dry powder formulations include drying techniques (i.e., spray drying and freeze drying), in vitro and in vivo aerosolization studies, solid state characterization methods, surface characterization techniques, particle size analysis, electron microscopy, in vitro dissolution and drug release studies, in vitro acellular, in vitro cellular, and in vivo animal studies.

Project summary

Nanocomposite Dry Powder Particles for Inhalation Delivery of Combination Anti-Cancer Drugs

Lung cancer is a leading cancer killer worldwide and the American Cancer Society estimates about 130,180 deaths from lung cancer in 2022. The lack of effective first-line chemotherapeutics, the existence of resistant tumors, and the non-optimal route of administration contribute to poor prognosis and high mortality in lung cancer. The addition of localized delivery of anti-cancer drugs via pulmonary route to the systemic delivery could allow a therapeutic intensification due to a loco-regional diffusion of the drug close to the tumor, while fighting invasive and diffuse cancerous cells. Literature reports suggest inhalation delivery of a combination of docetaxel with a nonsteroidal anti-inflammatory drug, celecoxib showed anticancer activity through cell proliferation inhibition and induction of apoptosis, along with reduced gastrointestinal toxicity. This study aims to develop highly aerosolizable, stable nanocomposite dry powder particles loaded with docetaxel and celecoxib for inhalation delivery. We hypothesize that the nanocomposite dry powder particles disintegrate in the lung lining fluid upon deposition and produce nanoparticles, which will escape alveolar macrophage uptake and release the drug in controlled manner for prolonged periods of time. Nanocomposite dry powder particles will be produced from nanoparticle suspension using a binder (leucine or trileucine) by spray drying approach. The produced powders will be characterized for solid state nature, in vitro aerosolization behavior, in vitro drug release and stability at accelerated conditions. Our lab has demonstrated expertise in producing dry powder formulations of anti-cancer drugs using spray drying technique and has all facilities to characterize the formulations. Following the success of this study, I plan to evaluate formulation tolerability of a most promising dry powder formulation in a small group of Sprague Dawley rats (male, 280-350 g, 3-4 weeks) intratracheally using a dry powder insufflator, Penn-Century Dry Powder Insufflator -Model DP-4R (Penn Century Inc., Wyndmoor, PA, USA) and in vivo studies using an animal model of lung cancer in future.

Career Development Award Proposal

Career Goal(s):
My goal is to become an independent academic investigator in the field of pharmaceutical sciences and a leader in pulmonary drug delivery research with an aim to deliver drugs in a targeted manner to treat the localized lung diseases. With this interest, I did a Ph.D. on various strategies to improve the residence time of the inhaled drug particles in the lungs. As a Postdoctoral Research Associate (Jul 2020-Feb 2022 at the University of Arizona) and Research Assistant Professor, my current position since Feb 2022 in Prof. Heidi M. Mansour’s lab, my current research focuses on the development and evaluation (physicochemical and biological) of novel inhalable drug formulations for treating lung conditions. Continuing my progress towards my career goal will require additional training in improving my research skills, writing grant applications, and collaborations with multidisciplinary research teams.
This project will allow me to improve my research skills in engineering nano-composite dry powder particles with better dispersibility. The extensive training in research methods and co-supervision skills that I received while earning a Ph.D. and postdoctoral training has provided the necessary foundation for me to be able to lead the proposed research project and advance my development as an independent investigator. The success of this project will build my confidence in developing my own research ideas and securing more grants particularly from the National Institutes of Health (NIH) to reach my career goal as an academic investigator. The presentation of this work at inhalation research conferences such as Drug Delivery to the Lungs, Respiratory Drug Delivery and International Society for Aerosols in Medicine (ISAM) would expand my scientific network and collaborations with multidisciplinary research teams.

Project Background:
Lung cancer is the leading cause of cancer death worldwide. The American Cancer Society estimates 1 in 16 people will be diagnosed with lung cancer in their lifetime.1 Combination drug therapies are being explored, as the synergistic action of multiple drugs could potentially lead to better therapeutic efficacy and reduced opportunity for the development of drug resistance by the cancer cells.2 However, the systemic routes of administration are limited by off-target toxicity and poor pulmonary selectivity of the drug combinations used, leading to low therapeutic efficacy.3
Several programs are currently investigating pulmonary delivery of anti-cancer drugs via inhalation.4 Pulmonary delivery of drugs has several advantages over conventional treatment, including a) being non-invasive, b) circumventing first pass metabolism and systemic toxicity, c) reducing the frequency of administration, and d) higher local drug concentrations. Among several pulmonary drug delivery systems, biodegradable nanoparticles have demonstrated several advantages in terms of protecting the active ingredient from degradation and releasing the drug in controlled manner for prolonged periods of time.5 Although few attempts have been made to deliver anticancer agents using nanoparticles and liposomes via inhalation route, the major limitations of these systems are instability during nebulization, biodegradability, drug leakage and associated drug adverse side effects.6,7 Other issue with nanoparticle pulmonary delivery is that their size is not suitable for deep lung deposition.
In my proposed study, I aim to develop nanocomposite dry powder particles loaded with two anti-cancer drugs, docetaxel and celecoxib which have synergistic action for treatment of lung cancer.8-10 Nanocomposite particles consist of drug-loaded nanoparticles and excipients. Nanoparticles are combined with the binder to render micron-sized particles of 3 μm size, which is the most effective dimension to deposit deep into lungs. After deposition in the surface fluid layer of alveoli, the complex is designed to liberate primary drug-loaded nanoparticles.11 Having deposited beyond the mucociliary escalator, the drug-loaded nanoparticles are sized to avoid recognition of alveolar macrophages and delivered near the lung epithelium for uptake and prolonged lung residence.