Dry powder formulation of azithromycin for COVID-19 therapeutics

Chan, S.H.Y., Sheikh, K., Zariwala, M. and Somavarapu, S. 2023. Dry powder formulation of azithromycin for COVID-19 therapeutics. Journal of Microencapsulation. 40 (4), pp. 217-232. https://doi.org/10.1080/02652048.2023.2175924

TitleDry powder formulation of azithromycin for COVID-19 therapeutics
TypeJournal article
AuthorsChan, S.H.Y., Sheikh, K., Zariwala, M. and Somavarapu, S.
Abstract

Azithromycin is an antibiotic proposed as a treatment for the coronavirus disease 2019 (COVID-19) due to its immunomodulatory activity. The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there was an improvement in dispersibility of the chitosan-related formulations. It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggested the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19.

Keywords Antibiotic
azithromycin
COVID-19
chitosan
dry powder inhaler
dry powder formulations
poly(lactic-co-glycolic acid) (PLGA)
nanocomposite microparticles
nanoparticles
pulmonary drug delivery
JournalJournal of Microencapsulation
Journal citation40 (4), pp. 217-232
ISSN1464-5246
Year2023
PublisherTaylor & Francis
Publisher's version
License
CC BY-NC-ND 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1080/02652048.2023.2175924
Web address (URL)https://www.tandfonline.com/doi/full/10.1080/02652048.2023.2175924#abstract
Publication dates
Published27 Mar 2023

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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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