Back to Browse Journals » International Journal of Nanomedicine » Volume 2 » Issue 4

Nano-liposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary pharmacokinetics

Authors Mahavir Chougule, Bijay Padhi, Ambikanandan Misra

Published Date January 2007 Volume 2007:2(4) Pages 675—688

DOI

Published 28 January 2007

Mahavir Chougule, Bijay Padhi, Ambikanandan Misra

TIFAC-CORE in NDDS, Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, India

Abstract: The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% ± 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 ± 0.8 µm, maximum fine particle fraction (FPF) of 71.1 ± 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 ± 0.1 µm, and geometric standard deviation (GSD) 1.7 ± 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi’s Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection.

Keywords: lung transplant rejection, tacrolimus, nano-liposomes, spray drying, dry powder inhaler

 

Download Article [PDF] 

Readers of this article also read:

Wearing-off in Parkinson’s disease: neuropsychological differences between on and off periods

Caillava-Santos F, Margis R, Rieder CR

Neuropsychiatric Disease and Treatment 2015, 11:1175-1180

Published Date: 13 May 2015

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li XS, Gao L, Zheng LB, Kou JY, Zhu X, Jiang YQ, Zhong ZY, Dan JH, Xu HB, Yang Y, Li H, Shi S, Cao WW, Zhao YJ, Tian Y, Yang LM

International Journal of Nanomedicine 2015, 10:821-838

Published Date: 22 January 2015

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

Wang Z, Mu HJ, Zhang XM, Ma PK, Lian SN, Zhang FP, Chu SY, Zhang WW, Wang AP, Wang WY, Sun KX

International Journal of Nanomedicine 2015, 10:633-644

Published Date: 14 January 2015

Vincristine sulfate liposomal injection for acute lymphoblastic leukemia [Corrigendum]

Soosay Raj TA, Smith AM, Moore AS

International Journal of Nanomedicine 2013, 8:4705-4706

Published Date: 5 December 2013

Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin

Zhang KC, Lv SW, Li XY, Feng YF, Li X, Liu L, Li S, Li YJ

International Journal of Nanomedicine 2013, 8:3227-3239

Published Date: 22 August 2013

Actively-targeted LTVSPWY peptide-modified magnetic nanoparticles for tumor imaging

Jie L-Y, Cai L-L, Wang L-J, Ying X-Y, Yu R-S, Zhang M-M,Du Y-Z

International Journal of Nanomedicine 2012, 7:3981-3989

Published Date: 24 July 2012

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

Luo H, Jiang B, Li B, Li Z, Jiang BH, Chen YC

International Journal of Nanomedicine 2012, 7:3951-3959

Published Date: 24 July 2012

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Manoharan Y, Ji Q, Yamazaki T, Chinnathambi S, Chen S, Ganesan S, Hill JP, Ariga K, Hanagata N

International Journal of Nanomedicine 2012, 7:3625-3635

Published Date: 16 July 2012