Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties.

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While realistic in vitro tests may produce results that correspond to drug deposition in vivo, MT model selection was most important for the MDI and SMI, but much less important than inhalation strength for the DPI.

Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed.

The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration.

The present study focuses on the development of multi-trigger responsive surface active lipid nanovesicles encapsulating paclitaxel with the hypothesis that pulmonary surfactant mimetic lipid vesicles sensitive to temperature and enzyme simultaneously will offer synergistic advantage towards improved therapeutic efficacy of paclitaxel via aerosol administration. The nanovesicles showed a unimodal size distribution of the particles (100-150 nm) and high encapsulation efficiency of paclitaxel (82%). Triggered release of paclitaxel was observed at ∼42 °C in the presence of secretory phospholipase A(2) enzyme with maximum release observed with both the triggers used simultaneously. Since these nanovesicles are intended for aerosol administration in the treatment of lung cancer, they were engineered to have high surface activity and airway patency, in order to mimic pulmonary surfactant functions. High deposition of nanovesicles in the lower impingement chamber of a twin impinger upon nebulization suggested them to be capable of reaching the terminal regions of the lungs. Nanovesicles showed facilitated and ATP dependent active uptake by A549 cells. The cytotoxic potential of the nanovesicles was significantly increased upon simultaneous use of both the triggers with an IC(50) of 49.3 nM. Overall, these studies suggest the therapeutic potential and advantages of multi trigger responsive lipid nanovesicles with encapsulated paclitaxel over that of the commercially available form of paclitaxel namely Taxol, and suggests the feasibility of aerosol administration in the treatment of lung cancer and pulmonary metastasis.

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