Pulmonary drug delivery

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Pulmonary drug delivery system and its advantages

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Perfluorocompounds usage in the pulmonary drug delivery : 

Perfluorocompounds usage in the pulmonary drug delivery PRESENTING BY: Palacharla Sridivya GIET School of Pharmacy, Rajahmundry, Andhra Pradesh,India M.D.Dhanaraju, principal , GIET School of pharmacy, Rajahmundry.

ABSTRACT : 

ABSTRACT Acute respiratory distress syndrome (ARDS) is a life threatening form of lung injury that results from an impairment of gas exchange due to fluid buildup in the lung. Several experimental treatment modalities are under investigation to reduce the mortality in ARDS patients, including “liquid ventilation” with a biocompatible perfluorocarbon compound (PFC). During liquid ventilation, the diseased lung is partially or totally filled with a PFC. Both animal and clinical studies suggest that liquid ventilation can recruit alveolar volume and facilitate gas exchange in the diseased lung. There is also evidence that PFCs can decrease the inflammatory response characteristic for ARDS and less severe forms of acute lung injury. In this presentation we discuss about the use of perfluorocarbon compounds in the treatment of acute respiratory distress syndrome(ARDS).

Acute respiratory distress syndrome (ARDS) : 

Acute respiratory distress syndrome (ARDS) life threatening form of lung injury that results from an impairment of gas exchange due to fluid buildup in the lung. Role of pulmonary surfactants in ARDS: Pulmonary surfactant plays an important role in lung function by lining alveoli and reducing surface tension at the air-liquid interface.  It is essential for proper lung function and reduces the work of breathing by increasing lung compliance.  Disruption of the surfactant system leads to lung dysfunction and lowered pulmonary compliance: both characteristics of ARDS.

Liquid ventilation technique used to treat ARDS : 

Liquid ventilation technique used to treat ARDS Done with a biocompatible perfluorocarbon compound (PFC). During liquid ventilation, the diseased lung is partially or totally filled with a PFC. recruit alveolar volume and facilitate gas exchange in the diseased lung. PFCs can decrease the inflammatory response characteristic for ARDS and less severe forms of acute lung injury.

Struture of perfluorocarbons : 

Struture of perfluorocarbons

Advantages of PFC's in liquid ventilation : 

Advantages of PFC's in liquid ventilation PFCs used during liquid ventilation are perfluorinated aliphatic compounds (i.e., all hydrogen atoms in the molecule are replaced by fluorine) that have a high solubility for oxygen and carbon dioxide. They are evenly distributed in the lung due to unique properties, such as low surface tension low viscosity high spreading coefficients high density.

1) Intrapulmonary drug administration is expected to achieve higher drug concentrations in the lung.2) At the same time, the even distribution of the PFC in the lung would result in a homogenous distribution of the drug.3) Furthermore, PFCs can deliver drugs to diseased parts of the lung by displacing fluid present in the diseased lung because of their higher density and immiscibility with water. : 

1) Intrapulmonary drug administration is expected to achieve higher drug concentrations in the lung.2) At the same time, the even distribution of the PFC in the lung would result in a homogenous distribution of the drug.3) Furthermore, PFCs can deliver drugs to diseased parts of the lung by displacing fluid present in the diseased lung because of their higher density and immiscibility with water.

Disadvantage of PFC's : 

Disadvantage of PFC's PFCs are extremely poor solvents for typical drug molecules. This represents a challenge for using PFCs as vehicles for the pulmonary administration of drugs. Their systemic uptake is minimal because of their low solubility in water, biological fats and lipids.

Enhancing solvent character of PFC'S : 

Enhancing solvent character of PFC'S Include dispersions of aqueous drug solutions or solid drug particles, PFC-soluble prodrugs and reverse (water-in-PFC) emulsions. dispersions of aqueous drug solutions or solid drug particles, PFC-soluble prodrugs and reverse (water-in-PFC) emulsions are used. “bulk flow turbulent mixing” in the lung to achieve a homogeneous distribution of the drug in the lung. Solubility of some drugs can be enhanced by covalently attaching a perfluoroalkyl moiety to the parent drug molecule.

Use of nano particles in liquid ventilation : 

Use of nano particles in liquid ventilation porous nanoparticles of drugs have been developed to obtain stable dispersions of the drug in the PFC. These novel dispersions allow a more controlled administration of the drug to the lung.

Slide 11: 

a PFC-soluble prodrug can be administered to the diseased lung where it is expected to partition into lung tissue and release the parent drug by chemical or biological degradation. prodrugs of nicotinic acid are soluble in PFCs. Furthermore, they can release the parent drug, nicotinic acid, and increase cellular levels of NAD.

Use of water in PFC micro emulsions to treat lungs : 

Use of water in PFC micro emulsions to treat lungs reverse water-in-PFC (micro-)emulsions have potential to administer typical drug molecules to the diseased lung. The goal of this approach is to dissolve the drug in the aqueous phase of the (micro-)emulsion while retaining desired properties such as high fluidity and high solubility for oxygen and carbon dioxide. only fluorinated dimorpholinophosphates have been reported to form biocompatible reverse water-in-PFC (micro-)emulsions. The emulsions can dissolve clinically relevant concentrations of a broad range of drugs and are stable for extended periods of time.

conclusion : 

conclusion use of PERFLUOROCARBON COMPOUNDS is very beneficial in pulmonary drug delivery. Especially it is used in the treatment of acute respiratory distress syndrome. Still it is away from the clinical application due to some disadvantages. Devlopment should be made in pulmonary drug delivery to improve its application to the patients.

References : 

References Amberson WR, Jennings JJ, Rhode CM. Clinical experience withhemoglobin-saline solutions, American Journal of Physiology, vol-1, 1949 page no- 469-489. 2. Lee R, Atsumi N, Jacobs EEJ, Austen WG, Vlahakes GJ.Ultrapure, stroma-free, polymerized bovine hemoglobin solution: evaluation ofrenal toxicity, Journal of Surgical Research. Issue 47, 1989,page no-407-411. 3. Amberson W, Flexner J, Steggerda FR, et al. On the use ofRinger-Locke solutions containing hemoglobin as a substitute for normal bloodin mammals, Journal of Cellular and Comparative Physiology, issue 5,1937, page no 359-382. 4. Tremper KK, Lapin R, Levine E, Friedman A, Shoemaker WC.Hemodynamic and oxygen transport effects of a perfluorochemical bloodsubstitute, Fluosol-DA (20%). Critical Care Medicine, issue 8 1980, page no -738-741. 5. Tremper KK, Friedman AE, Levine EM, Lapin R, Camarillo D. The preoperative treatment of severely anemic patients with a perfluorochemical oxygen-transport fluid, Fluosol-DA, New England Journal of Medicine. Issue 307 1982, page no- 277-283. 6. Teicher B. Use of perfluorocarbon emulsions in cancertherapy. In: Chang TMS, ed. Blood Substitutes and Oxygen Carriers. NewYork: Marcel Dekker, Inc, 1993, page no- 640-647.

THANKS TO PHARMAINFO.NET FOR GIVING THIS VALUABLE OPPORTUNITY : 

THANKS TO PHARMAINFO.NET FOR GIVING THIS VALUABLE OPPORTUNITY