<p>Docetaxel-Loaded Cholesterol-PEG Co-Modified Poly (n-Butyl) Cyanoacrylate Nanoparticles for Antitumor Drug Pulmonary Delivery: Preparation, Characterization, and in vivo Evaluation</p>

Abstract

Background and Aim: Polymeric nanoparticles (NPs) have received much attention as promising carrier systems in lung cancer and brain metastases. Methods: Here, for the first time, we investigated the feasibility of using inhaled cholesterol-PEG co-modified poly (n-butyl) cyanoacrylate NPs (CLS-PEG NPs) of docetaxel (DTX) for sustained pulmonary drug delivery in cancer metastasis. Results: Spray-dried or freeze-dried NPs yielded sustained drug release in vitro. In vitro inhalation evaluation data indicated that the inhalation formulation had better inhalability. Compared with intravenous (IV) administration, pharmacokinetic data suggested that the inhalation formulation prolonged plasma concentration of DTX for greater than 24 h and is more quickly and completely absorbed into the rat lung after intratracheal (IT) administration. Furthermore, freeze-dried powders were found to increase the t 1/2 and area under curve (AUC) by 2.3 and 6.5 fold compared to the free drug after IT administration, and spray-dried powders were found to increase the t 1/2 and AUC by 3.4 and 8.8 fold, respectively. After pulmonary administration of the inhalation formulation, DTX appeared to prolong the pulmonary absorption time. In addition, the inhalation formulation was distributed to the brain in a sustained release manner. Conclusion: These experimental results demonstrated that freeze-and spray-dried powders have the potential for pulmonary sustained release, and they also have the potential to be used as a novel treatment for the delivery of drugs that pass through the air-blood barrier and enter the brain and are efficient carriers for the treatment of brain metastasis.

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“…The particles’ aerodynamic assessment indicated 4.20 μm of MMAD with a geometric standard deviation (GSD) of 4.44 and an FPF of 59.44%. The above results indicated that the use of 10% leucine in the formulation was more inhalable when administered via an inhaler …”

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“…Finally, there is significant variation in the volume of the release medium across literature. Some studies have utilized a very high volume (e.g., 200 mL [ 21 , 29 ]) of release medium which significantly deviates from the volume of human lung lining fluid; 10 – 30 mL is generally considered for better correlation with the clinical application of inhalable nanoparticle-based powders [ 109 ]. As with redispersibility studies, in vitro drug release studies should be performed in biorelevant media such as PBS or SLF.…”

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