Targeting COPD with PLGA-Based Nanoparticles: Current Status and Prospects

Abstract

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.

Figure 1

The pathophysiologic processes involved in COPD. Pollutants, cigarette smoke, and biomass induce excessive generation of oxidative and nitrosative stresses including superoxide, nitric oxide, and peroxynitrite radicals. These radicals further activate the p38MAPK and NF-κB proteins which then upregulate the expression of genes and proteins involved in the inflammatory pathway. Additionally, smoke and pollutants also induce TLR signaling and initiate the inflammatory response by augmenting the expression of proinflammatory mediators. This led to the rapid infiltration of innate immune cells including neutrophils, macrophages, and lymphocytes. These cells release many proteases which stimulate mucus hypersecretion in COPD patients.

Figure 2

Applications of drug-loaded PLGA NP. PLGA NP loaded with drugs have been shown to be promising agents as antibacterial, adjuvant and immune-stimulator, antioxidant, anti-inflammatory, anticancer, antiviral, antifungal, and wound healer.

Figure 3

Types of PLGA NP-drug conjugates used in the treatment of COPD. PLGA NPs engineered with RNA and small-molecule drugs have been shown to have a protective role in COPD.

Figure 4

Variants of polymeric PLGA particles for drug delivery in lung diseases [, , , –, –97]. The green box denotes “yes” and the red box denotes “no”.

Figure 5

Delivery of PLGA NP-drug conjugates in COPD. Upon pulmonary administration, PLGA NP-drug conjugates reach the lungs and cross the blood capillary to move towards the alveoli.