Nanotechnology-Assisted Metered-Dose Inhalers (MDIs) for High-Performance Pulmonary Drug Delivery Applications

Abstract

Purpose: Respiratory disorders pose a major threat to the morbidity and mortality to public health. Here we reviewed the nanotechnology based pulmonary drug delivery using metered dose inhalers.

Methods: Major respiratory diseases such as chronic obstructive pulmonary diseases (COPD), asthma, acute lower respiratory tract infections, tuberculosis (TB) and lung cancer. At present, common treatments for respiratory disorders include surgery, radiation, immunotherapy, and chemotherapy or a combination. The major challenge is development of systemic delivery of the chemotherapeutic agents to the respiratory system. Conventional delivery of chemotherapy has various limitation and adverse side effected. Hence, targeted, and systemic delivery need to be developed. Towards this direction nanotechnology, based controlled, targeted, and systemic drug delivery systems are potential candidate to enhance therapeutic efficacy with minimum side effect. Among different route of administration, pulmonary delivery has unique benefits such as circumvents first pass hepatic metabolism and reduces dose and side effects.

Results: Respiratory disorders pose a major threat to the morbidity and mortality to public health globally. Pulmonary delivery can be achieved through various drug delivery devices such as nebulizers, dry powder inhalers, and metered dose inhalers. Among them, metered dose inhalers are the most interesting and first choice of clinician over others. This review focused on nanotechnology based pulmonary drug delivery using metered dose inhalers. This report focused on delivery of various types of therapeutics using nanocarriers such as polymeric nanoparticles and micelles, dendrimers, lipid nanocarriers such as liposomes, solid lipid nanostructures and nanostructured lipid carriers, and other using metered dose inhalers discussed comprehensively. This report provides insight about the effect of parameters of MDI such as co-solvent, propellants, actuators shape, nozzle diameters, and jet lengths, and respiratory flow rate, and particle size of co-suspension of drug on aerodynamics and lung deposition of formulation. This review also provided the insight about various metered dose inhalers market scenario and digital metered dose inhalers.

Conclusion: This report concluded the clinical potential of metered dose inhalers, summary of current progress and future perspectives towards the smart digital metered dose inhalers development.

Keywords: cancer; drug delivery; metered dose inhalers; nanocarriers; pulmonary delivery.

Fig. 1

Schematic of nanotechnology based pulmonary drug delivery system using metered dose inhalers to treat various respiratory disorders, advantages, and marketed devices. Reproduced with permission from ref. (–31). Copyright 2020 Springer open access, 2019 Elsevier, 2020 Springer, 2021 Elsevier, and 2021 MDPI Open access respectively.

Fig. 2

various nanocarrier used to deliver the therapeutics using metered dose inhaler. Reproduced with permission from ref. (27). Copyright 2020 Springer open access.

Fig. 3

Schematic view of delivery of therapeutics through loading into the polymeric nanoparticles by metered dose inhaler. Reproduced with permission from ref. (28). Copyright 2019 Elsevier.

Fig. 4

Fine particle fraction of pMDI formulations of a) chitosan and chitosan–PEG nanoparticles, b) formulations using cineole, cineole:n-heptane 9:1 and cineole:n-heptane 4:1, during 26-week storage. The schematic diagram about the forming process of ARM-NPs. (A) The TBA/water 1:4 system; (B) the TBA/water 3:2 system; (1) before freeze-drying; (2) during freeze-drying; (3) after adding ethanol absolute. Reproduced with permission from ref. (–76). Copyright 2012, 2012, 2016, Elsevier, Elsevier, Taylor & Frances respectively.

Fig. 5

Mechanism of formation of polymeric micelles. Reproduced with permission from ref. (29). Copyright 2020 Springer.

Fig. 6

various biomedical applications of dendrimers. Reproduced with permission from ref. (30). Copyright 2021 Elsevier.

Fig. 7

Schematic presentation of different lipid nanocarriers. Reproduced with permission from ref. (31). Copyright 2021 MDPI Open Access.

Fig. 8

Schematic of the interactive mechanism of the sibenadet hydrochloride—only formulation and sibenadet hydrochloride: micronized particulates formulations. Numbers in brackets are surface energy of interaction in mJ/m². Redesign the figure from ref. [102]. Copyright 2019 Elsevier.

Fig. 9

Discrete two-stage evaporation process for droplets from solution and suspension pMDI. Redesign the figure from ref. [112]. Copyright 2017 Elsevier.