Modern ways of doxicycline delivery and prospects of application in pharmacy

Keywords: doxycycline hyclate, drug delivery, dosage forms, sustained drug release, controlled release

Abstract

Currently, the global increase in resistance of pathogens to widely used antibiotics requires a return to the practice of using some classic drugs with preserved activity, finding new ways and directions of delivery of antibiotics to the locations of pathogenic microorganisms and the use of antimicrobial drugs that are not yet resistant. Doxycycline refers to antimicrobial drugs that do not yet have widespread resistance. Numerous studies of doxycycline have now been described as enhancing therapeutic effects, including COVID-19-related diseases, and finding new delivery routes to limit systemic side effects associated with high doses and avoid antibiotic resistance.

The aim of the work was to analyze modern ways of doxycycline delivery, to determine the prospects for use in pharmacy, to summarize and systematize data on its functional purpose in the development of drugs with specified pharmaco-technological parameters.

It is established that in the Ukrainian pharmaceutical market the range of drugs based on doxycycline hyclate is represented only by solid oral dosage forms - tablets and capsules for immediate release, but in the global pharmaceutical market there are additional dosage forms that provide parenteral delivery of doxycycline and oral forms. suspensions, syrups, dispersed tablets and delayed-release dosage forms – tablets, capsules and granules, which are the basis for the development of domestic drugs based on doxycycline.

Development of new dosage forms with modified DH, such as implants, aerosols, lyophilisate for solution for injection, development of new manufacturing technologies, selection of excipients and delivery systems can improve the pharmacological action of antibiotics by reducing the dose and frequency of administration, prolonged or controlled programming. , and expanding the range of therapeutic action.

Doxycycline is promising in pharmaceutical practice for the treatment of COVID-19, both due to its ability to inhibit matrix metalloproteinases (MMPs) and antiviral activity, especially against Mycoplasma pneumoniae, which is a secondary bacterial cause of pneumonia during the COVID-19 pandemic.

References

Ventola C. L. The antibiotic resistance crisis: part 1: causes and threats // P T. – 2015. – V. 40, N 4. – P. 277–283. PMID: 25859123; PMCID: PMC4378521

Davies J. Where have All the Antibiotics Gone? // The Canadian J. Infectious Diseases Med. Microbial. – 2006. – V. 17, N 5. – P. 287–290. https://doi.org/10.1155/2006/707296. PMID: 18382641

Douafer H., Andrieu V., Wafo E., Brunel J. M. Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections // Int. J. Pharmac., Elsevier. – 2020. – V. 586. – P. 119548. https://doi.org/10.1016/j.ijpharm.2020.119548. hal-03085007f

Zhanel G. G., Homenuik K., Nichol K. et al. The Glycylcyclines: A Comparative Review with the Tetracyclines // Drugs. – 2004. – V. 64. – P. 63–88.

Holmes N. E., Charles P. G. P. Safety and Efficacy Review of Doxycycline // Clin. Med. Insights: Therapeutics. – 2009. https://doi.org/10.4137/CMT.S2035

Schroeder C., Chowdhury I., Narra H. et al. Human rickettsioses: Host response and molecular pathogenesis // In Rickettsiales: Biology, Molecular Biology, Epidemiology, and Vaccine Development. – 2016. – P. 399–446. Springer International Publishing. https://doi.org/ 10.1007/978-3-319-46859-4_19

Yates P. A., Newman S. A., Oshry L. J. et al. Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease // Therapeutic Advances in Respiratory Disease. – 2020. – V. 14. – P. 1753466620951053. https://doi.org/10.1177/1753466620951053. PMID: 32873175; PMCID: PMC7476338

COVID-19 rapid guideline: managing suspected or confirmed pneumonia in adults in the community (NG165). NICE guideline. Published: 3 Ap ril 2020/ www.nice.org.uk/guidance/ng165 [Elektronnyi resurs]. – URL: https://www.nice.org.uk/guidance/ng165/resources/ covid19-rapid-guideline-managing-suspected-or-confirmed-pneumonia-in-adults-in-the-community -pdf-66141902429125

Derzhavnyi reiestr likarskykh zasobiv Ukrainy. – URL: http://www.drlz.kiev.ua/

Sloan B., Scheinfeld N. The use and safety of doxycycline hyclate and other second-generation tetracyclines // Expert Opinion on Drug Safety. – 2008. – V. 7. – P. 571–577. https://doi.org/10.1517/14740338.7.5.571

Rusu A., Buta E. L. The Development of Third-Generation Tetracycline Antibiotics and New Perspectives // Pharmaceutics. – 2021. – V. 13. – P. 2085. https://doi.org/10.3390/ pharmaceutics13122085

Heinemann F. W., Leypold C. F., Roman C. R. et al. X-Ray Crystallography of Tetracycline, Doxycycline and Sancycline // J. Chem. Crystallography. – 2013. – V. 43. – P. 213–222.

Farrah G., Tan E. The use of oral antibiotics in treating acne vulgaris: A new approach // Dermatol. Therapy. – 2016. – V. 29. – P. 377–384. https://doi.org/10.1111/dth.12370.

Manning M. W., Cassis L. A., Daugherty A. Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms // Arteriosclerosis, Thrombosis, and Vascular Biology. – 2003. – V. 23. – P. 483–488.

Salii O. O., Kuryshko H. H., Oherenko Z. O., Hetalo O. V. Porivnialni doslidzhennia profiliv vyvilnennia doksytsyklinu khiklatu z tverdykh zhelatynovykh kapsul pry zmini vyrobnykiv diiuchoi rechovyny // Visn.Kyivskoho nats. un-tu tekhnolohii ta dyzainu. Seriia Tekhnichni nauky. – 2020. – № 3 (146). – S. 165–174. https://doi.org/10.30857/1813-6796.2020.3.14

Smith R., Russo J., Fiegel J., Brogden N. Antibiotic delivery strategies to treat skin infections when innate antimicrobial defense fails // Antibiotics. – 2020. – V. 9 (2), N 56. – P. 1–25. https://doi.org/10.3390/antibiotics9020056

Aliyah A., Oktaviana W. W., Dwipayanti K. S. et al. Enhanced skin localization of doxycycline using microparticles and hydrogel: Effect of oleic acid as penetration enhancer // Pharmaciana. – 2021. – V. 11. – P. 239. https://doi.org/10.12928/pharmaciana.v11i2.21044

Abundo R., Corrente G., Perelli M. et al. Topical doxycycline after nonsurgical instrumentation of deep periodontal pockets: Results from a prospective case series with 12 months’ follow-up // J. Oral Sci. Rehabilitation. – 2019. – V. 5, Iss. 4. – Р. 38-42.

Omolu A., Bailly M., Day R. M. Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity // Drug Delivery. – 2017. – V. 24, N. 1. – P. 942–951. https://doi.org/10.1080/10717544.2017.1337826

Chushenko V. M., Yarnykh T. H., Rukhmakova O. A., Yurʼieva H. B. Udoskonalennia skladu i rozrobka ekstemporalnoi tekhnolohii pesariiv iz doksytsyklinom khiklatom na osnovi masla kakao // Farmats. chasopys. – 2020. – № 1. – S. 35–41. https://doi.org/10.11603/2312-0967.2020.1.10979

Tata P. R., Pardo-Saganta A., Prabhu M. et al. Airway-specific inducible transgene expression using aerosolized doxycycline // Amer. J. Respiratory Cell Mol. Biol. – 2013. – V. 49, N 6. – P. 1048–1056. https://doi.org/10.1165/rcmb.2012-0412OC

Saliy E. A., Honcharuk A. Yu., Hetalo O. V., Tarasenko A. V. Razrabotka y otsenka lyofylyzyrovannoho poroshka dlia pryhotovlenyia rastvora dlia ynektsyi na osnove doksytsyklyna // Vestn. Farmatsyy. – 2021. – № 3 (93). – S. 53–63. https://doi.org/10.52540/2074-9457.2021.3.53

Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis (DOXY). – 2018 [Електронний ресурс]. – Режим доступу: https://clinicaltrials.gov /ct2/show/NCT03479502

Haddada M. B., Jeannot K., Spadavecchia J. Novel Synthesis and Characterization of Doxycycline-Loaded Gold Nanoparticles: The Golden Doxycycline for Antibacterial Applications // Particle & Particle Systems Characterizatio. – 2019. – V. 36. – P. 1800395. https://doi.org/10.1002/ppsc.201800395

Petrescu M., Mitran R.-A., Luchian N A.-M. et al. Mesoporous ceria-silica composites as carriers for doxycycline // U. P. B. Scientific Bulletin, Series B: Chemistry and Materials Science. – 2015. – V. 77, N 3. – P. 13–24.

Kazek-Kęsik A., Nosol A., Płonka J. et al. Physico-chemical and biological evaluation of doxycycline loaded into hybrid oxide-polymer layer on Ti–Mo alloy // Bioactive Materials. – 2020. – V. 5, Iss. 3. – P. 553–563. https://doi.org/10.1016/j.bioactmat.2020.04.009

Rebekah K. Franklin, Sarah A. Marcus, Adel M. Talaat et al. A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of Mycobacterium smegmatis Infection // Drug Metabolism and Disposition: the Biological Fate of Chemicals. – 2015. – V. 43, N 8. – P. 1236–1245. https://doi.org/10.1124/dmd.115.063602

Rajendran V., Singh C., Ghosh P. C. Improved efficacy of doxycycline in liposomes against Plasmodium falciparum in culture and Plasmodium berghei infection in mice // Canadian J. Physiol. Pharmacol. – 2018. – V. 96, N 11. – P. 1145–1152. https://doi.org/10.1139/cjpp-2018-0067

Birtia G., Mahapatra S. K. Study of the Antibacterial Activity of a New Prolonged-Release Dental Dosage form Containing Doxycycline and Lidocaine // J. Pharmac. Res. Inter. – 2020. – V. 32, N 36. – P. 62–72. https://doi.org/10.9734/jpri/2020/v32i3630993

Mahmud R., Rahman M. M., Alam I. et al. Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial // J. Inter. Med. Res. 2021. – V. 49, N 5. – P. 3000605211013550. https://doi.org/10.1177/03000605211013550

Malek A. E., Granwehr B. P., Kontoyiannis D. P. Doxycycline as a potential partner of COVID-19 therapies // IDCases. – 2020. – V. 21, N 2020. – P. e00864. https://doi.org/10.1016/j.idcr.2020.e00864

Published
2022-08-29
How to Cite
Saliy, O. O., Sachenko, Y. V., Palchevska, T. A., & Strashnyi, V. V. (2022). Modern ways of doxicycline delivery and prospects of application in pharmacy. Farmatsevtychnyi Zhurnal, (4), 50-61. https://doi.org/10.32352/0367-3057.4.22.06
Section
Pharmaceutical technology