Pulmonary Delivery of Therapeutic Compounds for Treating CNS Disorders

Abstract

Delivering therapeutic compounds via the lungs presents potential advantages relative to other routes of administration. Depending on the compound and the disease state, these advantages may include: non-invasive medication delivery, ease of administration, higher bioavailability leading to dose sparing and lower systemic toxicity, potentially greater blood–brain barrier penetration and rapid pharmacodynamic effect. The practice of inhaling drugs has been around for centuries, including both medical and recreational usage. It is only more recently that formal clinical development programs have been undertaken specifically to use medication delivery via the lung to achieve systemic blood levels for the treatment of CNS disorders. At present, there are several CNS therapies being developed for pulmonary administration, with some of those programs at or near the marketing authorization stage. While there are still regulatory hurdles before these therapies can be put into practice, the success of these programs thus far demonstrates the scientific viability of inhalation therapies for treating CNS disorders.

In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery

“…Therefore, novel brain targeting DDS are required to overcome this barrier and to enhance drug potential to treat CNS diseases [ 2 , 3 ]. The advantages of pulmonary DDS over oral delivery, such as rapid absorption and onset, enhance drug transport across the BBB when formulated in suitable sized and lipophilic aerosolized particles [ 4 ]. Promising outcomes for delivering CNS therapeutics via the lungs with the aid of different inhaler technologies have been reported for Parkinson’s disease [ 5 ], anxiety [ 6 ], analgesia [ 7 ], and migraine [ 8 ].…”

Quantitative expression of human drug transporter proteins in lung tissues: Analysis of regional, gender, and interindividual differences by liquid chromatography–tandem mass spectrometry

“…Inhalation drugs have been used to topically treat pulmonary diseases, such as lung cancer, asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Aerosol inhalation is also one of the most promising alternatives to oral and other invasive routes of administration for systemic circulation drug delivery 1–4. The advantages of the pulmonary route are fast absorption, rapid onset of pharmacological action, and avoidance of hepatic and intestinal first‐pass metabolism 5.…”

Advancements in the Design and Development of Dry Powder Inhalers and Potential Implications for Generic Development

“…The Staccato device stands out among other inhalation devices due to its drug delivery mechanism. The device uses breath actuation, where an inhalation sensor triggers a heating element on the device that heats up a thin film of the formulation, causing it to sublimate and aerosolize the dose as dry particles [122]. Notably, the Staccato device's use of a thin film formulation makes it distinct from other carrier-based DPI formulations as the formulation is not in a powder form prior to actuation.…”