Glucocorticoids (GCs) have been used clinically for decades as potent anti-inflammatory and immunosuppressive agents. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of glucocorticoid resistance (GCR). Therefore, efforts to understand the complex mechanisms underlying GC function and GCR are ongoing. The goal is to generate new glucocorticoid receptor (GR) ligands that can dissociate anti-inflammatory from metabolic side effects and/or overcome GCR. In this review paper we discuss recent insights into GR-mediated actions in GCR and novel therapeutic strategies for acute and chronic inflammatory diseases.

Therapeutic Mechanisms of Glucocorticoids.

Delivery strategies for sustained drug release in the lungs.

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines.

Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetic profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety in the lungs, which is closely linked to lung retention times. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments for several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps.

/pdf/polymer-drug-conjugates-as-inhalable-drug-delivery-systems-a-2k5idwub7c.pdf

Polymer-drug conjugates as inhalable drug delivery systems: A review

Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery. Therefore, particle-based delivery systems have emerged to minimize pulmonary clearance mechanisms, enhance drug therapeutic efficacy, and control the release behavior. A successful implementation of a particle-based delivery system requires understanding the influential parameters in terms of drug carrier, inhalation technology, and health status of the patient's respiratory system. This review aims at investigating the parameters that significantly drive the clinical outcomes o...

Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics.

Polyethylene glycol-drug ester conjugates for prolonged retention of small inhaled drugs in the lung

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Polyethylene glycol-drug ester conjugates for prolonged retention of small inhaled drugs in the lung