Study on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity

Papay, Z.E., Kosa, A., Boddi, B., Merchant, Z., Saleem, I.Y., Zariwala, M., Klebovich, I., Somavarapu, S. and Antal, I. 2017. Study on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity. Journal of Aerosol Medicine and Pulmonary Drug Delivery. 30 (4), pp. 274-288. https://doi.org/10.1089/jamp.2016.1316

TitleStudy on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity
AuthorsPapay, Z.E.
Kosa, A.
Boddi, B.
Merchant, Z.
Saleem, I.Y.
Zariwala, M.
Klebovich, I.
Somavarapu, S.
Antal, I.
Abstract

Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury (ALI).
Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations consist of nanoparticles (NPs) have several advantages over other administration routes therefore this study investigated the application of apigenin loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery.
Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction. The influence of dispersibility enhancers(lactose monohydrate and L-leucine) on the in vitro aerosol deposition using a next generation impactor (NGI) was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using Franz cell apparatus. The antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH˙) free radical scavenging assay.
Results: The encapsulation efficiency and the drug loading was measured to be 82.61 ± 4.56% and 7.51 ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray dried BSA-Api-NPs possessed good the aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose and fine particle fraction. The aerodynamic properties was enhanced by leucine and decreased by lactose, however, the dissolution was
reversely affected. The DPPH˙ assay confirmed that the antioxidant activity of encapsulated Api was preserved.
Conclusion: This study provides evidence to support that albumin nanoparticles 49 are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs is a novel delivery system against lung injury with potential antioxidant activity.

Keywordsflavonoid
apigenin
albumin nanoparticles
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Journal citation30 (4), pp. 274-288
ISSN1941-2711
Year2017
PublisherMary Ann Liebert
Accepted author manuscript
Digital Object Identifier (DOI)https://doi.org/10.1089/jamp.2016.1316
Publication dates
Published online10 Mar 2017
Published10 Mar 2017
Published in print01 Aug 2017

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Zariwala, M.G., Somavarapu, S., Farnaud, S. and Renshaw, D. 2013. Comparison study of iron preparations using a human intestinal model. Scientia Pharmaceutica. 81 (4), pp. 1123-1139. https://doi.org/10.3797/scipharm.1304-03

Increased transferrin-bound iron uptake in HepG2 cells is followed by an increase in expression of the iron hormone hepcidin pre-and post-translationally
Mehta, K., Patel, V., Busbridge Mark, Renshaw, D., Zariwala, M., Evans, R. and Farnaud, S. 2012. Increased transferrin-bound iron uptake in HepG2 cells is followed by an increase in expression of the iron hormone hepcidin pre-and post-translationally. European Iron Club Annual Meeting 2012. Rennes, France 29 - 31 Aug 2012

Comparison of iron absorption from iron supplement preparations using an in vitro Caco-2 model
Zariwala, M., Farnaud, S. and Renshaw, D. 2012. Comparison of iron absorption from iron supplement preparations using an in vitro Caco-2 model. European Iron Club Annual Meeting 2012. Rennes, France 29 - 31 Aug 2012

DPPIV and macronutrients regulate the expression of PYY3–36 in human gut epithelial cells
Kosicka, A., Renshaw, D. and Zariwala, M. 2012. DPPIV and macronutrients regulate the expression of PYY3–36 in human gut epithelial cells. Society for Endocrinology BES 2012. Harrogate, UK Mar - Apr 2012 BioScientifica Ltd.. https://doi.org/10.1530/endoabs.31.P197

Ac 2-26, an annexin A1-derived peptide, reduces inflammation in human SGBS adipocytes after hypoxia treatment
Kosicka-Knox, A., Cunliffe, A., Mackenzie, R., Zariwala, M. and Renshaw, D. 2012. Ac 2-26, an annexin A1-derived peptide, reduces inflammation in human SGBS adipocytes after hypoxia treatment. 15th International & 14th European Congress of Endocrinology. Florence, Italy 05 - 09 May 2012 BioScientifica Ltd..

Annexin A1, an anti-inflammatory regulator, is expressed in human adipocytes
Kosicka-Knox, A., Cunliffe, A., Mackenzie, R., Zariwala, M. and Renshaw, D. 2012. Annexin A1, an anti-inflammatory regulator, is expressed in human adipocytes. Society for Endocrinology BES 2012. Harrogate, UK Mar - Apr 2012

Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity
Holness, M.J., Zariwala, M., Walker, C.G. and Sugden, M.C. 2012. Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity. FEBS Open Bio. 2, pp. 32-36. https://doi.org/10.1016/j.fob.2012.02.003

Changes in adipocyte circadian clock function via SRT1 and AMPK in programmed obesity
Caton, P.W., Zariwala, M., Holness, M.J. and Sugden, M.C. 2010. Changes in adipocyte circadian clock function via SRT1 and AMPK in programmed obesity. Diabetic Medicine. 27 (S1), pp. 1-36. https://doi.org/10.1111/j.1464-5491.2009.02935.x

PPARalpha deficiency impacts the regulation ofadipocyte leptin synthesis and secretion
Holness, M.J., Zariwala, M., Walker, C.G. and Sugden, M.C. 2009. PPARalpha deficiency impacts the regulation ofadipocyte leptin synthesis and secretion. Diabetic Medicine. 26 (S1), pp. 37-38. https://doi.org/10.1111/j.1464-5491.2009.02662.x

The molecular regulation of adipose-tissue gene expression by an early life intervention
Sugden, M.C., Zariwala, M., Nooristani, S. and Holness, M.J. 2009. The molecular regulation of adipose-tissue gene expression by an early life intervention. Diabetic Medicine. 26 (S1), pp. 37-38. https://doi.org/10.1111/j.1464-5491.2009.02662.x

PPARs and the orchestration of metabolic fuel selection
Sugden, M.C., Zariwala, M.G. and Holness, M.J. 2009. PPARs and the orchestration of metabolic fuel selection. Pharmacological Research. 60 (3), p. 141–150. https://doi.org/10.1016/j.phrs.2009.03.014

Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion
Zariwala, M., Holness, M.J., Turner, M.D. and Sugden, M.C. 2007. Prolactin in culture leads to a shift in stimulatory threshold but does not augment the K-ATP channel independent pathway for glucose-stimulated insulin secretion. Diabetic Medicine. 24 (S1), p. 33. https://doi.org/10.1111/j.1464-5491.2007.02126.x

Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan
Pandit, S., Cevher, E, Zariwala, M., Somavarapu, S. and Alpar, H.O. 2007. Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan. Journal of Microencapsulation. 24 (6), p. 539–552. https://doi.org/10.1080/02652040701443700

Diet, obesity and diabetes: a current update
Walker, C.G., Zariwala, M.G., Holness, M.J. and Sugden, M.C. 2007. Diet, obesity and diabetes: a current update. Clinical Science. 112 (2), pp. 93-111. https://doi.org/10.1042/CS20060150

Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding
Zariwala, M., Holness, M.J. and Sugden, M.C. 2006. Early protein restriction attenuates effects of increased age to suppress the response of adipose-tissue LPL activity to feeding. Diabetic Medicine. 23 (S2), pp. 31-138. https://doi.org/10.1111/j.1466-5468.2006.01875.x

Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination following intranasal or intramuscular immunisation
Moschos, S.A., Bramwell, V.W., Somavarapu, S. and Alpar, H.O. 2005. Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination following intranasal or intramuscular immunisation. Vaccine. 23 (16), pp. 1923-1930. https://doi.org/10.1016/j.vaccine.2004.10.016

Adjuvant synergy: the effects of nasal coadministration of adjuvants
Moschos, S.A., Bramwell, V.W., Somavarapu, S. and Alpar, H.O. 2004. Adjuvant synergy: the effects of nasal coadministration of adjuvants. Immunology and Cell Biology. 82 (6), pp. 628-637. https://doi.org/10.1111/j.0818-9641.2004.01280.x

New strategies in vaccine research: targeting quorum sensing pathways for prophylaxis against antibiotic-resistant S. aureus infections
Moschos, S.A., Pandit, S., Somavarapu, S., Balaban, N. and Alpar, H.O. 2004. New strategies in vaccine research: targeting quorum sensing pathways for prophylaxis against antibiotic-resistant S. aureus infections. Proceedings of the 31st International Symposium for the Controlled Release of Bioactive Materials 2004. Honolulu, USA 12 - 16 Jun 2004 pp. 526

Immunogenicity of adjuvanted recombinant urease administered intranasally
Moschos, S.A., Somavarapu, S., Singh, J., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Immunogenicity of adjuvanted recombinant urease administered intranasally. Proceedings of the 28th International Symposium for the Controlled Release of Bioactive Materials. San Diego, USA 23 - 27 Jun 2001 pp. 7033

Immunogenicity of adjuvanted recombinant urease administered intra-muscularly
Moschos, S.A., Somavarapu, S., Eyles, J.E., McHugh, C., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Immunogenicity of adjuvanted recombinant urease administered intra-muscularly. Proceedings of the 28th International Symposium for the Controlled Release of Bioactive Materials. San Diego, USA 23 - 27 Jun 2001 pp. 7033

Evaluation of adjuvanted recombinant urease for effective immunization against Helicobacter pylori
Moschos, S.A., Somavarapu, S., Eyles, J.E., McHugh, C., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Evaluation of adjuvanted recombinant urease for effective immunization against Helicobacter pylori. Immunology. 104 (s1), p. 98. https://doi.org/10.1046/j.1365-2567.2001.1040s1070.x

Quil-A and MDP enhances the adjuvanticity of alum for intramuscular delivery of rURE
Moschos, S.A., Somavarapu, S., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Quil-A and MDP enhances the adjuvanticity of alum for intramuscular delivery of rURE. Immunology. 104 (s1), p. 98. https://doi.org/10.1046/j.1365-2567.2001.1040s1070.x

Microsphere encapsulated Diphtheria Toxoid induces protein secretion from in-vitro Peyers’ patches and in vivo
Turner, J.J., Somavarapu, S., Moschos, S.A., Randall, L., Simpkin, G. and Alpar, H.O. 2000. Microsphere encapsulated Diphtheria Toxoid induces protein secretion from in-vitro Peyers’ patches and in vivo. Proceedings of the 3rd World Meeting APV/APGI 2000. Berlin, Germany 3 - 6 Apr 2000 pp. 389-390

Novel protein secretion from both ex-vivo Peyers’ patches and in-vivo; induction by microsphere encapsulated diphtheria toxoid
Moschos, S.A., Somavarapu, S., Singh, J., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2000. Novel protein secretion from both ex-vivo Peyers’ patches and in-vivo; induction by microsphere encapsulated diphtheria toxoid. Proceedings of the 27th International Symposium for the Controlled Release of Bioactive Materials. Paris, France 09 - 13 Jul 2001 pp. 562-563

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