Encapsulation into PEG-Liposomes Does Not Improve the Bioavailability of Pulmonary Delivered Salmon Calcitonin

Autor: Janani Swaminathan, Carsten Ehrhardt, Oliviero L. Gobbo, Anne Marie Healy, Frederic Tewes
Přispěvatelé: School of Pharmacy and Pharmaceutical Sciences and Institute of Neuroscience, Trinity College Dublin, Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Pharmacy and Pharmaceutical Science [Dublin, Irlande], School of Pharmacy and Pharmaceutical Science
Rok vydání: 2014
Předmět:
Calcitonin
Male
Pulmonary and Respiratory Medicine
Surface Properties
Chemistry
Pharmaceutical
Biological Availability
Pharmaceutical Science
Breast Neoplasms
02 engineering and technology
Buffers
Pharmacology
030226 pharmacology & pharmacy
Polyethylene Glycols
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Cell Line
Tumor
Administration
Inhalation
Animals
Pharmacology (medical)
Particle Size
Rats
Wistar
Lung
ComputingMilieux_MISCELLANEOUS
Aerosolization
Drug Carriers
Liposome
Bone Density Conservation Agents
Inhalation
Chemistry
Nebulizers and Vaporizers
Vesicle
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Hydrogen-Ion Concentration
021001 nanoscience & nanotechnology
Controlled release
Rats
3. Good health
Bioavailability
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Area Under Curve
Delayed-Action Preparations
Injections
Intravenous
Liposomes
Female
Stress
Mechanical
0210 nano-technology
Drug carrier
Zdroj: JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, 2014, 27 (1), pp.1-11. ⟨10.1089/jamp.2013.1049⟩
ISSN: 1941-2703
1941-2711
DOI: 10.1089/jamp.2013.1049
Popis: Salmon calcitonin (sCT) is approved for the short-term treatment of Paget's disease and hypercalcemia. As pulmonary delivery might improve the drug's efficacy, a variety of liposomal sCT formulations for inhalation were prepared and characterized with the intention of developing a controlled release formulation.The influence of pH of the loading buffer, charge of the vesicular surface, and membrane rigidity on particle size, ζ-potential, and sCT encapsulation efficiency of formulations was studied. The most promising systems were investigated for their ability to withstand nebulization stresses using an Aeroneb(®) vibrating mesh device. In vitro studies were carried out to determine sCT release from the vesicles and the bioactivity of the peptide post nebulization. Lastly, pharmacokinetics of sCT liposomes following intratracheal aerosolization in an experimental rat model were investigated and compared with intravenous injection.Liposomes prepared with acidic loading buffer and comprising rigid lipid membranes showed an optimal compromise between small particle size, high encapsulation efficiency, and sCT stability. Polyethylene glycol (PEG) liposomes showed the highest encapsulation efficiency overall, regardless of the ζ-potential of the vesicles. Positive surface charge, however, yielded higher entrapment in non-PEGylated liposomes. All liposomes tested were stable during nebulization. The bioactivity of sCT after formulation into liposomes was 52-55%. Intratracheal nebulization in rats revealed that the bioavailability and other pharmacokinetic parameters were not enhanced by liposomes, when compared with sCT solution. Following intravenous administration, however, liposomes showed significantly higher bioavailability and AUCinf (area under the curve to the infinity time point) than controls.The developed liposomal formulations were not optimal carriers for pulmonary delivery of sCT. Due to the low amounts of peptide released from the vesicles, enzymatic digestion by peptidases in the airspace reduced the bioavailability significantly. Liposomal encapsulation of sCT, nevertheless, resulted in improved pharmacokinetics following injection.
Databáze: OpenAIRE
Externí odkaz: