Pulmonary Targeting of Levofloxacin Using Microsphere-Based Dry Powder Inhalation
The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were fabricated by solvent evaporation technique. Central Composite Design (CCD) was adopted to optimize the microspheres, with desired particle size, drug loading, and drug entrapment efficiency, for targeting alveolar macrophages via non-invasive pulmonary delivery. Structural characterization studies by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction analysis revealed the absence of any possible chemical interaction between the drug and the polymer used for the preparation of microspheres. In addition, the optimized drug-loaded microspheres exhibited desired average aerodynamic diameter of 2.13 ± 1.24 μm and fine particle fraction of 75.35 ± 1.42%, indicating good aerosolization properties. In vivo data demonstrated that LVX-loaded microspheres had superior lung accumulation, as evident by a two-fold increase in the area under the curve AUC0-24h, as compared with plain LVX. Furthermore, LVX-loaded microspheres prolonged drug residence time in the lung and maintained a relatively high drug concentration for a longer time, which contributed to a reduced leakage in the systemic circulation. In conclusion, inhalable LVX-loaded microspheres might represent a plausible delivery vehicle for targeting pulmonary tuberculosis via enhancing the therapeutic efficacy of LVX while minimizing its systemic off-target side effects.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Pharmaceuticals (Basel, Switzerland) - 15(2022), 5 vom: 30. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Al Hagbani, Turki [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Inhalable microspheres |
|---|
| Anmerkungen: |
Date Revised 16.07.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/ph15050560 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341536660 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341536660 | ||
| 003 | DE-627 | ||
| 005 | 20231226012015.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ph15050560 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1138.xml |
| 035 | |a (DE-627)NLM341536660 | ||
| 035 | |a (NLM)35631386 | ||
| 035 | |a (PII)560 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Al Hagbani, Turki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pulmonary Targeting of Levofloxacin Using Microsphere-Based Dry Powder Inhalation |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were fabricated by solvent evaporation technique. Central Composite Design (CCD) was adopted to optimize the microspheres, with desired particle size, drug loading, and drug entrapment efficiency, for targeting alveolar macrophages via non-invasive pulmonary delivery. Structural characterization studies by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction analysis revealed the absence of any possible chemical interaction between the drug and the polymer used for the preparation of microspheres. In addition, the optimized drug-loaded microspheres exhibited desired average aerodynamic diameter of 2.13 ± 1.24 μm and fine particle fraction of 75.35 ± 1.42%, indicating good aerosolization properties. In vivo data demonstrated that LVX-loaded microspheres had superior lung accumulation, as evident by a two-fold increase in the area under the curve AUC0-24h, as compared with plain LVX. Furthermore, LVX-loaded microspheres prolonged drug residence time in the lung and maintained a relatively high drug concentration for a longer time, which contributed to a reduced leakage in the systemic circulation. In conclusion, inhalable LVX-loaded microspheres might represent a plausible delivery vehicle for targeting pulmonary tuberculosis via enhancing the therapeutic efficacy of LVX while minimizing its systemic off-target side effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a inhalable microspheres | |
| 650 | 4 | |a levofloxacin | |
| 650 | 4 | |a lung targeting | |
| 650 | 4 | |a pulmonary drug delivery | |
| 650 | 4 | |a tuberculosis | |
| 700 | 1 | |a Vishwa, Bhavya |e verfasserin |4 aut | |
| 700 | 1 | |a Abu Lila, Amr S |e verfasserin |4 aut | |
| 700 | 1 | |a Alotaibi, Hadil Faris |e verfasserin |4 aut | |
| 700 | 1 | |a Khafagy, El-Sayed |e verfasserin |4 aut | |
| 700 | 1 | |a Moin, Afrasim |e verfasserin |4 aut | |
| 700 | 1 | |a Gowda, Devegowda V |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceuticals (Basel, Switzerland) |d 2009 |g 15(2022), 5 vom: 30. Apr. |w (DE-627)NLM199619514 |x 1424-8247 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2022 |g number:5 |g day:30 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ph15050560 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2022 |e 5 |b 30 |c 04 | ||