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Cytokines and Alveolar Type II Cells
Published in Jason Kelley, Cytokines of the Lung, 2022
Alveolar type II cells synthesize, store, and secrete the surface active material that lines the alveolar space and stabilizes the alveolus at low lung volumes by decreasing the surface tension of the alveolar lining fluid. This material is composed of lipids, proteins, and carbohydrates. Approximately 70–80% of the phospholipid in surfactant is phosphatidylcholine, and phosphatidylglycerol is the second major phospholipid component (Rooney, 1985). Dipalmitoylphosphatidylcholine composes 50–60% of the phosphatidyl-choline and is thought to be the major phospholipid species responsible for the stability of the surface active material lining the alveolar space (Wright and Clements, 1987; Clements and Tierney, 1965). The alveolar type II cell is the major source of surface active material within the lung. The biosynthetic pathways, metabolism, secretion, and uptake of surfactant by alveolar type II cells have been extensively reviewed (Rooney, 1985; Wright and Clements, 1987; Wright, 1990; Chander and Fisher, 1990; Mendelson and Boggaram, 1990). This chapter will focus on the effect of cytokines and hormones on surfactant biosynthesis and secretion by alveolar type II cells (Table 1). Pharmacologic agents used to stimulate surfactant synthesis or secretion will not be reviewed.
Fetal Circulation
Published in Miriam Katz, Israel Meizner, Vaclav Insler, Fetal Well-Being, 2019
Miriam Katz, Israel Meizner, Vaclav Insler
Out of the total amount of phosphatidylcholine, 62.9% is DPPC (dipalmitoyl-phosphatidylcholine). This led to a conclusion that palmitic acid is an essential component of the surface active material,40 and has a stabilizing effect on lecithin.
Particle Engineering Technology for Inhaled Therapies
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
David Lechuga-Ballesteros, Susan Hoe, Benjamin W. Maynor
The use of phospholipids is widespread in the formulation of intravenous oncology therapies (e.g. Doxil®), where the composition of liposomes is designed to encapsulate the cytotoxic drug, modify absorption, distribution, metabolism, and excretion (ADME) characteristics, and thus improve the safety and efficacy of the drug. Given the proliferation of saturated and unsaturated phospholipids in mammalian lung surfactant (see Table 14.2), phospholipids are also an excipient option for inhalation. Phospholipids have successfully been used to manufacture liposomal dispersions for pulmonary delivery. Inhaled dipalmitoyl phosphatidylcholine (DPPC) is used as a lung surfactant in a formulation (Survanta®) for prevention and treatment of respiratory distress syndrome in premature newborns. Linhaliq® and Lipoquin®liposomal ciprofloxacin for nebulization (HSPC:Chol) and Insmed’s ALIS (Amikacin liposomal inhalation solution) (DPPC:Chol 2:1 neutrally charged) are two other examples of inhaled phospholipid formulations. Liposomal dispersions have been proven ideal to increase the residence time of the drug in the lung and thereby frequency of administration and increase local effect, properties advantageous for inhaled antibiotics for lung infections (Cipolla et al. 2014).
A technology evaluation of CVT-301 (Inbrija): an inhalable therapy for treatment of Parkinson’s disease
Published in Expert Opinion on Drug Delivery, 2021
Michael M. Lipp, Anthony J. Hickey, Robert Langer, Peter A. LeWitt
Preclinical studies were initially conducted in multiple animal species to demonstrate proof of concept of this approach as well as to identify a formulation suitable for clinical and commercial development. Initial studies conducted in a rat model of PD demonstrated that the pulmonary administration of 2 mg of levodopa resulted in a rapid elevation of plasma concentrations, whereas oral levodopa administration results in a slower rise in plasma concentrations [31]. Similar pharmacokinetic results were seen in beagle dogs, which also demonstrated that inhaled levodopa was absorbed in a more rapid and less variable manner compared with oral administration [32]. Throughout these studies, formulations with increasing loads of levodopa were developed in order to account for expected human dosing levels and to provide for dosing with a maximum of 2 inhalations per dose. The clinical dose of levodopa was adjusted throughout the clinical program via varying the capsule fill weight and/or number of capsules administered per dose. An excipient in the inhaled formulation is dipalmitoyl phosphatidylcholine, the main endogenous constituent of pulmonary surfactant and crucial for lung function, whose function is to lower the surface tension in the alveoli [33,34].
Fabrication of versatile targeted lipopolymersomes for improved camptothecin efficacy against colon adenocarcinoma in vitro and in vivo
Published in Expert Opinion on Drug Delivery, 2021
Mahsa Zahiri, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, Mona Alibolandi
Camptothecin was obtained from Tocris Bioscience Co., Ltd. (Ellisville, USA). Dipalmitoylphosphatidylcholine (DPPC) was obtained from Avanti Polar Lipids (Alabama, USA). Methoxy poly-(ethylene glycol) (Mw = 2000 Da), 1,1ʹ-dioctadecyl-3,3,3ʹ,3ʹ-tetramethylindocarbocyanine perchlorate (DiI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were obtained from Sigma–Aldrich (Schnelldorf, Germany). Poly(L-lactide)3000-PEGm2000 and Poly(L-lactide)3000-PEG-MAL2000 were prepared from Nano Soft Polymers (Winston-Salem, USA). Roswell Park Memorial Institute-1640 (RPMI-1640) medium, penicillin-streptomycin solution, trypsin and fetal bovine serum (FBS) were acquired from GIBCO (Darmstadt, Germany). C26 (murine colon carcinoma cells), HT29 (human colon adenocarcinoma), and CHO (Chinese hamster ovary) cell lines were supplied by Pasteur Institute of Iran (Tehran, Iran). Other solvents and chemical reagents applied in this project were procured from Merck & Co (Darmstadt, Germany). All chemicals with analytical grade were utilized without further purification. The AS1411 aptamer [SH-5-(GGTGGTGGTGGTTGTGGTGGTGGTGG)-3′] was acquired from Microsynth AG (Balgach, Switzerland).
Kinetic Deposition of Polar and Non-polar Lipids on Silicone Hydrogel Contact Lenses
Published in Current Eye Research, 2020
Doerte Luensmann, Negar Babaei Omali, Adeline Suko, Elizabeth Drolle, Miriam Heynen, Lakshman N. Subbaraman, Charley Scales, Zohra Fadli, Lyndon Jones
The competitive uptake of different tear components to the different lenses can further impact the amount of deposition of individual components. Tam et al.46 conducted a similar in vitro study compared to the current one and reported on the 16 hour time point for radiolabeled dipalmitoylphosphatidylcholine and cholesterol. Their ATS solution did not match the reported human tear composition, as significantly lower concentrations of protein and slightly higher concentrations of lipids were used, which resulted in an uptake of these polar and non-polar lipids that was at least 10x higher for senofilcon A, lotrafilcon B, and comfilcon A lenses compared to the current study. Tam et al.46 were also able to show that multipurpose care regimens removed no more than 3% of lipid deposition after 16 hours of incubation in ATS. This lack in removal efficiency would explain why lipid deposition increased over time for the polar and non-polar lipids in the current study, despite the daily use of a multipurpose care regimen (Figure 1–3).