Evaluation of single-dose inhalation of clarithromycin-loaded solid lipid nanoparticles in rat model
Öz
This study aimed to explore the effective utilization of clarithromycin (CLA) through the development of clarithromycin-loaded solid lipid nanoparticles (CLA-loaded SLN), designed for nebulizer-based delivery for the first time. Wistar albino rats were divided into seven groups (n=8) based on time points (0.5, 1, 2, 4, 12, 24 hours, and a control group). At the respective time points, lung tissues and blood samples were collected and analyzed for CLA concentrations using HPLC-MS/MS. The maximum serum concentration (Cmax) was 6.74 µg/mL, with average serum CLA concentrations of 5.06, 2.5, 2.18, 1.13, and 0.5 µg/mL across the groups. CLA was undetectable in the control group and in the serum of the last group. Using the linear trapezoidal method (LTM), the area under the curve (AUC 0-24) for serum CLA was calculated as 17.06 µg*h/mL. Significant differences (p<0.001) were observed between several groups in serum CLA levels. In lung tissue, the highest Cmax was 2.66 µg/g, with average concentrations of 1.99, 1.8, 1.76, 0.36, 0.14, and 0.04 µg/g. The AUC for lung CLA concentration was 7.43 µg*h/g. These findings indicate that inhalation of CLA-loaded SLN achieves adequate plasma concentrations and sustained lung tissue levels for up to 12 hours post-inhalation. However, serum CLA levels were undetectable after 12 hours. Accurate characterization may facilitate CLA's application as an inhalable therapy.
Anahtar Kelimeler
Clarithromycin Clarithromycin aerosol Drug exposure Single-dose pharmacokinetics Solid lipid nanoparticle inhaler drug
Proje Numarası
KBÜBAP-22-DS-041
Kaynakça
- Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. European journal of pharmaceutics and biopharmaceutics 2000;50(1):161-177.
- FDA U. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Food and Drug Administration Center for Drug Evaluation and Research, US Department of Health and Human Services. https://www. fda. gov/media/72309/download 2005.
- Ferrati S, Wu T, Kanapuram SR, Smyth HD. Dosing considerations for inhaled biologics. International journal of pharmaceutics 2018;549(1-2):58-66.
- Ashcroft RE. The declaration of Helsinki. The Oxford textbook of clinical research ethics 2008:141-148.
- Bosquillon C, Madlova M, Patel N, Clear N, Forbes B. A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture. Pharmaceutical research 2017;34(12):2532-2540.
- Buckley A, Hodgson A, Warren J, Guo C, Smith R. Size-dependent deposition of inhaled nanoparticles in the rat respiratory tract using a new nose-only exposure system. Aerosol Science and Technology 2016;50(1):1-10.
- Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. British journal of clinical pharmacology 2003;56(6):588-599.
- Wong BA. Inhalation exposure systems: design, methods and operation. Toxicologic pathology 2007;35(1):3-14.
- Kobuchi S, Fujita A, Kato A, Kobayashi H, Ito Y, Sakaeda T. Pharmacokinetics and lung distribution of macrolide antibiotics in sepsis model rats. Xenobiotica 2020;50(5):552-558.
- 1Kuehl PJ, Anderson TL, Candelaria G, Gershman B, Harlin K, Hesterman JY, Holmes T, Hoppin J, Lackas C, Norenberg JP. Regional particle size dependent deposition of inhaled aerosols in rats and mice. Inhalation toxicology 2012;24(1):27-35.
- 1Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical journal of pharmaceutical research 2013; 12(2), 265-273.
- 1Shrivastava P, Gautam L, Jain A, Vishwakarma N, Vyas S, Vyas SP. Lipid drug conjugates for improved therapeutic benefits. Current pharmaceutical design 2020; 26(27), 3187-3202.
- 1Cengiz M, Ayhanci A, Kutlu HM, Musmul A. Potential therapeutic effects of silymarin and silymarin-loaded solid lipidnanoparticles on experimental kidney damage in BALB/c mice: biochemical and histopathological evaluation. Turkish Journal of Biology 2016; 40(4), 807-814.
- Finlay WH. Deposition of aerosols in the lungs: Particle characteristics. Journal of Aerosol Medicine and Pulmonary Drug Delivery 2014; 34(4), 213-216.
- Madkhali OA. Perspectives and prospective on solid lipid nanoparticles as drug delivery systems. Molecules, 2022; 27(5), 1543.
- Park H, Otte A, Park K. Evolution of drug delivery systems: From 1950 to 2020 and beyond. Journal of Controlled Release 2022; 342, 53-65.
- Abdulbaqi IM, Assi RA, Yaghmur A, Darwis Y, Mohtar N, Parumasivam T, Wahab HA. Pulmonary delivery of anticancer drugs via lipid-based nanocarriers for the treatment of lung cancer: An update. Pharmaceuticals 2021; 14(8), 725.
- Leong EW, Ge R. Lipid nanoparticles as delivery vehicles for inhaled therapeutics. Biomedicines, 2022; 10(9), 2179.
- Cojocaru E, Petriș OR, Cojocaru C. Nanoparticle-based drug delivery systems in inhaled therapy: improving respiratory medicine. Pharmaceuticals 2024; 17(8), 1059.
Sıçan modelinde klaritromisin yüklü katı lipid nanopartiküllerinin tek doz inhalasyonunun değerlendirilmesi
Öz
Bu çalışmanın amacı, ilk kez nebülizatör tabanlı uygulama için tasarlanmış klaritromisin yüklü katı lipit nanopartiküllerinin (CLA-SLN) geliştirilmesi yoluyla CLA’nın etkin kullanımını araştırmaktır. Wistar albino sıçanları zaman noktalarına (0.5, 1, 2, 4, 12, 24 saat ve kontrol grubu) göre yedi gruba (n = 8) ayrıldı. İlgili zaman noktalarında, akciğer dokuları ve kan örnekleri toplandı ve HPLC-MS/MS kullanılarak CLA konsantrasyonları açısından analiz edildi. Maksimum serum konsantrasyonu (Cmax) 6,74 µg/mL iken, gruplar arasında ortalama serum CLA konsantrasyonları sırasıyla 5,06, 2,5, 2,18, 1,13 ve 0,5 µg/mL idi. CLA, kontrol grubunda ve son grubun serumunda tespit edilemedi. Doğrusal trapezoidal yöntem kullanılarak, serum CLA için eğri altında kalan alan (AUC 0-24) 17,06 µg*h/mL olarak hesaplandı. Serum CLA seviyelerinde birkaç grup arasında anlamlı farklılıklar (p<0.001) gözlendi. Akciğer dokusunda en yüksek Cmax 2,66 µg/g iken, ortalama konsantrasyonlar 1,99, 1,8, 1,76, 0,36, 0,14 ve 0,04 µg/g idi. Akciğer CLA konsantrasyonu için AUC 7,43 µg*h/g idi. Bu bulgular, CLA yüklü SLN'nin inhalasyonunun yeterli plazma konsantrasyonlarına ulaştığını ve inhalasyondan sonra 12 saate kadar akciğer dokusu seviyelerinin devam ettiğini göstermektedir. Ancak serum CLA düzeyleri 12 saat sonra tespit edilemedi. Doğru karakterizasyon CLA'nın inhalasyon tedavisi olarak uygulanmasını kolaylaştırabilir.
Anahtar Kelimeler
Klaritromisin Klaritromisin aerosol İlaç maruziyeti Tek doz farmakokinetiği Katı lipid nanopartikül inhaler ilacı
Proje Numarası
KBÜBAP-22-DS-041
Kaynakça
- Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. European journal of pharmaceutics and biopharmaceutics 2000;50(1):161-177.
- FDA U. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Food and Drug Administration Center for Drug Evaluation and Research, US Department of Health and Human Services. https://www. fda. gov/media/72309/download 2005.
- Ferrati S, Wu T, Kanapuram SR, Smyth HD. Dosing considerations for inhaled biologics. International journal of pharmaceutics 2018;549(1-2):58-66.
- Ashcroft RE. The declaration of Helsinki. The Oxford textbook of clinical research ethics 2008:141-148.
- Bosquillon C, Madlova M, Patel N, Clear N, Forbes B. A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture. Pharmaceutical research 2017;34(12):2532-2540.
- Buckley A, Hodgson A, Warren J, Guo C, Smith R. Size-dependent deposition of inhaled nanoparticles in the rat respiratory tract using a new nose-only exposure system. Aerosol Science and Technology 2016;50(1):1-10.
- Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. British journal of clinical pharmacology 2003;56(6):588-599.
- Wong BA. Inhalation exposure systems: design, methods and operation. Toxicologic pathology 2007;35(1):3-14.
- Kobuchi S, Fujita A, Kato A, Kobayashi H, Ito Y, Sakaeda T. Pharmacokinetics and lung distribution of macrolide antibiotics in sepsis model rats. Xenobiotica 2020;50(5):552-558.
- 1Kuehl PJ, Anderson TL, Candelaria G, Gershman B, Harlin K, Hesterman JY, Holmes T, Hoppin J, Lackas C, Norenberg JP. Regional particle size dependent deposition of inhaled aerosols in rats and mice. Inhalation toxicology 2012;24(1):27-35.
- 1Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical journal of pharmaceutical research 2013; 12(2), 265-273.
- 1Shrivastava P, Gautam L, Jain A, Vishwakarma N, Vyas S, Vyas SP. Lipid drug conjugates for improved therapeutic benefits. Current pharmaceutical design 2020; 26(27), 3187-3202.
- 1Cengiz M, Ayhanci A, Kutlu HM, Musmul A. Potential therapeutic effects of silymarin and silymarin-loaded solid lipidnanoparticles on experimental kidney damage in BALB/c mice: biochemical and histopathological evaluation. Turkish Journal of Biology 2016; 40(4), 807-814.
- Finlay WH. Deposition of aerosols in the lungs: Particle characteristics. Journal of Aerosol Medicine and Pulmonary Drug Delivery 2014; 34(4), 213-216.
- Madkhali OA. Perspectives and prospective on solid lipid nanoparticles as drug delivery systems. Molecules, 2022; 27(5), 1543.
- Park H, Otte A, Park K. Evolution of drug delivery systems: From 1950 to 2020 and beyond. Journal of Controlled Release 2022; 342, 53-65.
- Abdulbaqi IM, Assi RA, Yaghmur A, Darwis Y, Mohtar N, Parumasivam T, Wahab HA. Pulmonary delivery of anticancer drugs via lipid-based nanocarriers for the treatment of lung cancer: An update. Pharmaceuticals 2021; 14(8), 725.
- Leong EW, Ge R. Lipid nanoparticles as delivery vehicles for inhaled therapeutics. Biomedicines, 2022; 10(9), 2179.
- Cojocaru E, Petriș OR, Cojocaru C. Nanoparticle-based drug delivery systems in inhaled therapy: improving respiratory medicine. Pharmaceuticals 2024; 17(8), 1059.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Hayvan Bilimi (Diğer) |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | KBÜBAP-22-DS-041 |
| Erken Görünüm Tarihi | 23 Nisan 2025 |
| Yayımlanma Tarihi | 26 Nisan 2025 |
| Gönderilme Tarihi | 1 Aralık 2024 |
| Kabul Tarihi | 10 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 6 Sayı: 1 |
