Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

Abstract

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases. Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution, leading to a more effective therapy with reduced required doses and side effects. On the other hand, there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical, aerodynamic, and biological properties, which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result. Therefore, we focused on powders consisting of polysaccharides, lipids, proteins, or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers. We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms. This review paper addresses the most common manufacturing methods with novel modifications, pros and cons of different materials, drug loading capacities with release profiles, and biological properties such as cytocompatibility, bactericidal, or anticancer properties.

Behavior of Self‐Disintegrating Microparticles at the Air/Mucus Interface

“…NGI measurements offer strong indications for the clinical performance of a formulation, exhibiting a notable correlation with in vivo results. [ 70 ] The MMAD values of 6.7 and 7.2 μm determined here for the PLGA/lysine and PLGA–PDA/lysine h‐μPs, respectively, are slightly larger than the optimal range for alveolar deposition; accordingly, these h‐μPs are likely to impact in the central airways such as the bronchi and bronchioles. The GSD calculations indicate a favorable particle size distribution: the FPF is characterized as the proportion of particles possessing an aerodynamic diameter of <5 μm, whereas the FPD denotes the absolute mass of particles from the FPF across all stages of the NGI.…”

Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System

“…Several strategies that aimed to improve the targeting and effectiveness of drugs inhaled from DPIs were proposed using the functionalization of the surface of drug particles, which helps to increase both aerosolization and bioavailability. A recent overview by Knap et al [ 113 ] indicated various approaches of formulating solid inhalable drug microparticles using polysaccharides (e.g., chitosan and hyaluronic acid), lipids (for instance, PS phospholipids such as dipalmitoyl phosphatidylcholine, DPPC, or dipalmitoyl phosphatidylglycerol, DPPG), proteins (e.g., fibroin), or polymers (such as poly(lactide-co-glycolide), PLGA, or polycaprolactone, PCL). The obtained effect on their bioavailability can include tuning the residence time on the lung surface and/or the rate of uptake by alveolar macrophages (AMs).…”

Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System

“…Several strategies that aimed to improve the targeting and effectiveness of drugs inhaled from DPIs were proposed using the functionalization of the surface of drug particles, which helps to increase both aerosolization and bioavailability. A recent overview by Knap et al [113] indicated various approaches of formulating solid inhalable drug microparticles using polysaccharides (e.g., chitosan and hyaluronic acid), lipids (for instance, PS phospholipids such as dipalmitoyl phosphatidylcholine, DPPC, or dipalmitoyl phosphatidylglycerol, DPPG), proteins (e.g., fibroin), or polymers (such as poly(lactide-coglycolide), PLGA, or polycaprolactone, PCL). The obtained effect on their bioavailability can include tuning the residence time on the lung surface and/or the rate of uptake by alveolar macrophages (AMs).…”