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- Publisher Website: 10.1016/j.pupt.2013.07.010
- Scopus: eid_2-s2.0-84887990979
- PMID: 23933140
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Article: Inhalable DNase I microparticles engineered with biologically active excipients
Title | Inhalable DNase I microparticles engineered with biologically active excipients |
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Authors | |
Keywords | Cystic fibrosis Dextran DNase I Leucine Polyanions Pulmonary |
Issue Date | 2013 |
Citation | Pulmonary Pharmacology and Therapeutics, 2013, v. 26, n. 6, p. 700-709 How to Cite? |
Abstract | Highly viscous mucus poses a big challenge for the delivery of particulates carrying therapeutics to patients with cystic fibrosis. In this study, surface modifying DNase I loaded particles using different excipients to achieve better lung deposition, higher enzyme stability or better biological activity had been exploited. For the purpose, controlled release microparticles (MP) were prepared by co-spray drying DNase I with the polymer poly-lactic-co-glycolic acid (PLGA) and the biocompatible lipid surfactant 1,2-dipalmitoyl-Sn-phosphatidyl choline (DPPC) using various hydrophilic excipients. The effect of the included modifiers on the particle morphology, size, zeta potential as well as enzyme encapsulation efficiency, biological activity and release had been evaluated. Powder aerosolisation performance and particle phagocytosis by murine macrophages were also investigated. The results showed that more than 80% of enzyme activity was recovered after MP preparation and that selected surface modifiers greatly increased the enzyme encapsulation efficiency. The particle morphology was greatly modified altering in turn the powders inhalation indices where dextran, ovalbumin and chitosan hydrochloride increased considerably the respirable fraction compared to the normal hydrophilic carriers lactose and PVP. Despite of the improved aerosolisation caused by chitosan hydrochloride, yet retardation of chitosan coated particles in artificial mucus samples discouraged its application. On the other hand, dextran and polyanions enhanced DNase I effect in reducing cystic fibrosis mucus viscosity. DPPC proved good ability to reduce particles phagocytic uptake even in the presence of the selected adjuvants. The prepared MP systems were biocompatible with lung epithelial cells. To conclude, controlled release DNase I loaded PLGA-MP with high inhalation indices and enhanced mucolytic activity on CF sputum could be obtained by surface modifying the particles with PGA or dextran. © 2013 Elsevier Ltd. |
Persistent Identifier | http://hdl.handle.net/10722/349017 |
ISSN | 2023 Impact Factor: 3.3 2023 SCImago Journal Rankings: 0.786 |
DC Field | Value | Language |
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dc.contributor.author | Osman, Rihab | - |
dc.contributor.author | Al Jamal, Khuloud T. | - |
dc.contributor.author | Kan, Pei Lee | - |
dc.contributor.author | Awad, Gehanne | - |
dc.contributor.author | Mortada, Nahed | - |
dc.contributor.author | EL-Shamy, Abd Elhameed | - |
dc.contributor.author | Alpar, Oya | - |
dc.date.accessioned | 2024-10-17T06:55:42Z | - |
dc.date.available | 2024-10-17T06:55:42Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Pulmonary Pharmacology and Therapeutics, 2013, v. 26, n. 6, p. 700-709 | - |
dc.identifier.issn | 1094-5539 | - |
dc.identifier.uri | http://hdl.handle.net/10722/349017 | - |
dc.description.abstract | Highly viscous mucus poses a big challenge for the delivery of particulates carrying therapeutics to patients with cystic fibrosis. In this study, surface modifying DNase I loaded particles using different excipients to achieve better lung deposition, higher enzyme stability or better biological activity had been exploited. For the purpose, controlled release microparticles (MP) were prepared by co-spray drying DNase I with the polymer poly-lactic-co-glycolic acid (PLGA) and the biocompatible lipid surfactant 1,2-dipalmitoyl-Sn-phosphatidyl choline (DPPC) using various hydrophilic excipients. The effect of the included modifiers on the particle morphology, size, zeta potential as well as enzyme encapsulation efficiency, biological activity and release had been evaluated. Powder aerosolisation performance and particle phagocytosis by murine macrophages were also investigated. The results showed that more than 80% of enzyme activity was recovered after MP preparation and that selected surface modifiers greatly increased the enzyme encapsulation efficiency. The particle morphology was greatly modified altering in turn the powders inhalation indices where dextran, ovalbumin and chitosan hydrochloride increased considerably the respirable fraction compared to the normal hydrophilic carriers lactose and PVP. Despite of the improved aerosolisation caused by chitosan hydrochloride, yet retardation of chitosan coated particles in artificial mucus samples discouraged its application. On the other hand, dextran and polyanions enhanced DNase I effect in reducing cystic fibrosis mucus viscosity. DPPC proved good ability to reduce particles phagocytic uptake even in the presence of the selected adjuvants. The prepared MP systems were biocompatible with lung epithelial cells. To conclude, controlled release DNase I loaded PLGA-MP with high inhalation indices and enhanced mucolytic activity on CF sputum could be obtained by surface modifying the particles with PGA or dextran. © 2013 Elsevier Ltd. | - |
dc.language | eng | - |
dc.relation.ispartof | Pulmonary Pharmacology and Therapeutics | - |
dc.subject | Cystic fibrosis | - |
dc.subject | Dextran | - |
dc.subject | DNase I | - |
dc.subject | Leucine | - |
dc.subject | Polyanions | - |
dc.subject | Pulmonary | - |
dc.title | Inhalable DNase I microparticles engineered with biologically active excipients | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.pupt.2013.07.010 | - |
dc.identifier.pmid | 23933140 | - |
dc.identifier.scopus | eid_2-s2.0-84887990979 | - |
dc.identifier.volume | 26 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 700 | - |
dc.identifier.epage | 709 | - |
dc.identifier.eissn | 1522-9629 | - |