Research

Although many therapeutic agents have demonstrated efficacy, their use has been limited by pharmacokinetic constraints and associated adverse effects. To achieve the targeted delivery of therapeutic agents such as drugs, siRNA, or miRNA, the Innovative Bioengineering and Drug and Gene Delivery (iBDG) Lab is working on the development of multifunctional bioresponsive NCs, which will be selectively delivered to the site of action, i.e., disease tissue or cells, while sparing healthy tissues. We have developed NCs using biodegradable, safer natural polymers such as albumin, gelatin, and chitosan. In addition, we are developing engineered polymeric NCs and evaluating their physicochemical properties, efficacy in in vitro cell culture, and safety and efficacy in clinically relevant animal models.

Our multidisciplinary approach utilizes nanotechnology, engineering, drug discovery, and molecular biology techniques. By applying this approach, we can engineer the NCs to bypass the multiple clearance mechanisms in the human body and target the disease site to exert a therapeutic effect. We believe the targeted delivery of therapeutic agents using NCs via inhalation, parenteral, and oral routes to the site of action will improve the efficacy of treatment for pulmonary diseases (asthma, bacterial and viral infections, hypertension), cancers (lung cancer, breast cancer, mesothelioma, neuroblastoma), and minimize associated adverse side effects. In addition, the dose and dosing frequency can be reduced by increasing the blood circulation half-life, thereby improving patient compliance. Preclinical studies in in vitro cell culture and animal models will help evaluate the efficacy of the developed NCs. Our multifunctional bioresponsive drug and gene delivery systems would represent the next generation of therapies for cancer and pulmonary disorders. Our multifunctional bioresponsive drug and gene-based approaches and preclinical studies would form the framework for future clinical studies.

Polymer and lipid-based drug and/or gene delivery systems:

In collaboration with bioengineers, we have developed several polymeric materials for multifunctional drug and gene delivery systems. By introducing positively charged chemical functional groups, the neutral polymer was converted into a cationic polymer that could carry negatively charged siRNA/miRNA. The inclusion of disulfide bonds has enabled these polymers to target the glutathione-rich cytoplasm. Arginine-rich polymers have shown improved cell penetration. We have developed liposomes using endogenous lipids, NCs based on natural polymers such as albumin, gelatin, and chitosan, and bioengineered polymeric drug and gene delivery systems.

Fig. Scheme for formulation of matrix-based polymeric layer-by-layer nanocarriers

By utilizing these materials, we developed delivery systems that could deliver hydrophobic and hydrophilic therapeutic agents at the same time. Co-delivery of siRNA with small molecules has shown improved efficacy.

Fig. Formulation of siRNA loaded matrix-based polymeric nanocarriers.

Another focus is to enhance the delivery of NCs across the tumor or diseased tissue. The receptor targeting strategy has increased the specificity of drug or siRNA-loaded nanoparticulate-based delivery systems.

Inhalable drug and/or gene delivery systems

The research is focused on the development of inhalable formulations as alternative non-invasive delivery systems. We have engineered natural polymer- or phospholipid-based nanoparticles for the targeted delivery of drugs or siRNA to treat pulmonary disorders. We have also developed nanoliposomes which could deliver drug and or siRNA for specific diseased cells or tissue. We have developed nanosuspension-based nebulizers and dry powder inhaler products. Our group has developed dry powder inhaler products for the pharmaceutical industry, which were successfully transferred and adopted by the industry in their marketed products.

Figure. Extracellular extended release and antiviral mechanism of camostat (Camo) from nebulized Camo-PEG nanoliposomes (Camo-pegNLs)
(A) Following nebulization, Camo-pegNLs enable efficient deposition in the deep lung region, where released camostat inhibits TMPRSS2-mediated spike protein priming, reducing binding of the viral receptor-binding domain (RBD) to ACE2 receptors on lung epithelial cells and limiting viral infection. (B) Camo is released from Camo-pegNLs in a sustained, extended-release manner, maintaining therapeutic concentrations at the site of action and targeting TMPRSS2. (C) Inhibition of TMPRSS2 prevents proteolytic cleavage of the viral spike protein at the S2′ site, a critical step required for membrane fusion. (D) Consequently, viral attachment to ACE2 receptors is reduced, thereby blocking coronavirus entry into host lung cells. Kashikar R et.al. AAPS PharmSciTech, 2025, 26(5), 139, 1-18

Combination therapies

Combination therapy has shown their advantages on their efficacy against various diseases. We have developed a unique synergistically acting multi-pathway targeting combination of siRNA with small molecule drug.

We utilized targeted nano delivery system to further enhance the performance of this combination and thus to overcome the current limits, such as poor pharmacokinetic profile, low solubility or stability, severe adverse effect, etc., in the chemo and gene therapy.

Fig. Design of dual therapeutic agent loaded multifunctional receptor targeted nanocarriers. 

We have developed drug and gene delivery systems for the following diseases:

Pulmonary Diseases

Pulmonary diseases—including asthma, bacterial and viral infections, and pulmonary hypertension—pose significant global health challenges due to chronic inflammation, infection, and limited effectiveness of conventional therapies. Current treatments often focus on symptom management rather than addressing underlying disease mechanisms. Our research focuses on developing advanced drug and gene delivery systems to improve therapeutic outcomes in these conditions. We design lipidic and polymeric nanocarriers (NCs) for targeted delivery of drugs and genetic materials directly to affected lung tissues.

For asthma, we aim to modulate underlying immunological pathways responsible for airway inflammation and hyperresponsiveness. For bacterial and viral infections, including respiratory pathogens, our systems are engineered to enhance targeted delivery of antimicrobials and antivirals. For pulmonary hypertension, we are focused on delivering therapeutics that regulate vascular remodeling and improve lung function.

The goal is to develop targeted, efficient, and minimally invasive delivery strategies that enhance efficacy, reduce side effects, and improve patient quality of life.

Cancers

Cancers include lung cancer, breast cancer, mesothelioma, and neuroblastoma. Cancer remains a major cause of morbidity and mortality worldwide. Despite advances in treatment, challenges such as tumor heterogeneity, drug resistance, and systemic toxicity limit the effectiveness of conventional therapies, which often lack precise targeting of tumor cells. Our research focuses on developing conventional and advanced drug and gene delivery systems to improve therapeutic outcomes across these cancers. We design lipidic and polymeric nanocarriers (NCs) for the targeted delivery of chemotherapeutics and genetic materials directly to tumor tissues.

For lung cancer and mesothelioma, our systems aim to enhance localized delivery within the lung environment. In breast cancer, we emphasize conventional parenteral and oral routes, as well as receptor-mediated targeting, including HER2-specific approaches, and natural product combinations to improve selectivity. For neuroblastoma, we focus on delivering gene-based and combination therapies to overcome resistance and improve treatment response.
The goal is to discover, develop, and evaluate drug and gene delivery strategies that enhance therapeutic efficacy, reduce side effects, and support the translation of these technologies into clinical cancer treatments.

Skin Disorders – Topical and Transdermal Delivery

Skin disorders such as psoriasis and atopic dermatitis often show suboptimal clinical outcomes with current therapies. Our research focuses on developing nanocarrier (NC)-based systems for topical drug delivery to enhance therapeutic effectiveness and improve patient outcomes. In addition, a magnesium cream formulation developed in our laboratory has been successfully commercialized by the Center for Magnesium Education and Research, LLC. We are also advancing transdermal delivery strategies using human skin–based permeation and molecular studies to improve the delivery of therapeutic agents across the skin barrier.