Comprehensive Assessment of Transcorneal Permeation, Antimicrobial, and Antifungal Activities of Andrographolide-Loaded Nanosuspension: In vitro and In vivo Studies
Abstract
This study aimed to comprehensively assess the transcorneal permeation, antimicrobial, and antifungal activities of a nanosuspension loaded with Andrographolide, a promising herbal compound. Through a combination of in vitro and in vivo studies, the efficacy, and potential applications of the nanosuspension in ocular drug delivery were investigated. In the in vitro phase, transcorneal permeation studies were conducted using Franz diffusion cells with excised rabbit corneas. The nanosuspension demonstrated significantly enhanced permeation compared to a control formulation, indicating its ability to effectively deliver Andrographolide through the cornea and into the ocular tissues. Additionally, the nanosuspension exhibited potent antimicrobial and antifungal activities against various ocular pathogens, as determined by agar diffusion and broth microdilution assays. Building upon the promising in vitro results, in vivo studies were performed using a rabbit model. Ocular tolerability of the nanosuspension was assessed through eye observations, with no observed signs of irritation or adverse effects. Furthermore, the nanosuspension's in vivo antimicrobial and antifungal activities were evaluated by instilling the formulation into the rabbits' eyes and monitoring conjunctival congestion and inflammation. The results demonstrated a significant reduction in conjunctival congestion, highlighting the nanosuspension's potential for combating ocular infections and inflammation. The comprehensive assessment presented in this study establishes the transcorneal permeation capability of the Andrographolide-loaded nanosuspension and its remarkable antimicrobial and antifungal activities. These findings underscore the potential of the nanosuspension as an effective ocular drug delivery system for various ocular infections and inflammatory conditions. The study contributes to the development of novel therapeutic approaches in ophthalmology, aiming to improve patient outcomes and provide alternative treatment options for ocular diseases.
Keywords: Transcorneal permeation; Nanosuspension; Andrographolide; Antimicrobial activity; Antifungal activity; Ocular drug delivery
Keywords:
Transcorneal permeation, Nanosuspension, Andrographolide, Antimicrobial activity, Antifungal activity, Ocular drug deliveryDOI
https://doi.org/10.22270/jddt.v13i6.5847References
Reviews RJC and M, 1990 undefined. Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Springer; Available from: https://link.springer.com/article/10.1007/BF00046364
Karimi M, Sahandi Zangabad P, Ghasemi A, Amiri M, Bahrami M, Malekzad H, et al. Temperature-Responsive Smart Nanocarriers for Delivery of Therapeutic Agents: Applications and Recent Advances. ACS Appl Mater Interfaces. 2016 Aug 24; 8(33):21107-33. https://doi.org/10.1021/acsami.6b00371
Discovery BRN reviews D, 2004 undefined. Nanosuspensions in drug delivery. nature.com; Available from: https://www.nature.com/articles/nrd1494
Kumar S, Burgess DJ. Nanosuspensions. Long Acting Injections and Implants. 2012; 239-61. https://doi.org/10.1007/978-1-4614-0554-2_13
Casamonti M, Risaliti L, Vanti G, Engineering VP, 2019 undefined. Andrographolide loaded in micro-and nano-formulations: Improved bioavailability, target-tissue distribution, and efficacy of the "king of bitters". Elsevier [Internet]. [cited 2023 May 20]; Available from: https://www.sciencedirect.com/science/article/pii/S209580991830996
Elsheikh MA, Rizk SA, Elnaggar YSR, Abdallah OY. Nanoemulsomes for Enhanced Oral Bioavailability of the Anticancer Phytochemical Andrographolide: Characterization and Pharmacokinetics. AAPS PharmSciTech. 2021 Oct 1; 22(7). https://doi.org/10.1208/s12249-021-02112-9
Chellampillai B, Pawar AP. Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles. Eur J Drug Metab Pharmacokinet. 2011 Jan; 5(3-4):123-9. https://doi.org/10.1007/s13318-010-0016-7
Abdelrahman A, Salem H, … RKJ of pharmaceutical, 2015 undefined. Modeling, optimization, and in vitro corneal permeation of chitosan-lomefloxacin HCl nanosuspension intended for ophthalmic delivery. Springer; Available from: https://link.springer.com/article/10.1007/s12247-015-9224-7 https://doi.org/10.1007/s12247-015-9224-7
Peter S, Mathews MM, Saju F, Paul S. Development, Optimization and In Vitro Characterization of Eudragit-Ganciclovir Nanosuspension or Treating Herpes Simplex Keratitis. J Pharm Innov. 2023; https://doi.org/10.1007/s12247-023-09723-8
Jadhav PA, Yadav A V. Design, development and characterization of ketorolac tromethamine polymeric nanosuspension. Ther Deliv. 2019; 10(9):585-97. https://doi.org/10.4155/tde-2019-0045
Abdelrahman AA, Salem HF, Khallaf RA, Ali AMA. Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery. J Pharm Innov. 2015 Sep 7; 10(3):254-68. https://doi.org/10.1007/s12247-015-9224-7
Deore B, Mahajan H, Res UDIJCT, 2009 undefined. Development and characterization of sustained release microspheres by quasi emulsion solvent diffusion method. researchgate.net 2009; 1(3):634-42. Available from: https://www.researchgate.net/profile/Hitendra-Mahajan/publication/278961934_Development_and_characterization_of_sustained_release_microspheres_by_quasi_emulsion_solvent_diffusion_method/links/5587e3ad08aeb0cdade0e989/Development-and-characterization-of-sustained-release-microspheres-by-quasi-emulsion-solvent-diffusion-method.pdf
You J, Han X, Wang Y, Yang L, Yu Y, B QLC and S, et al. -release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0927776506000105
Kawashima Y, Niwa T, Handa T, … HTJ of, 1989 undefined. Preparation of controlled-release microspheres of ibuprofen with acrylic polymers by a novel quasi-emulsion solvent diffusion method. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0022354915478827 https://doi.org/10.1002/jps.2600780118
Yang M, You B, Fan Y, Wang L, Yue P, of HYI journal, et al. Preparation of sustained-release nitrendipine microspheres with Eudragit RS and Aerosil using quasi-emulsion solvent diffusion method. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0378517303002096
Sieg J, Sciences JRJ of P, 1981 undefined. Mechanistic studies on transcorneal permeation of fluorometholone. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0022354915438614 https://doi.org/10.1002/jps.2600700915
Bijl P Van Der, Eyk A van, Cornea DM, 2001 undefined. Effects of three penetration enhancers on transcorneal permeation of cyclosporine. journals.lww.com; Available from: https://journals.lww.com/corneajrnl/fulltext/2001/07000/effects_of_three_penetration_enhancers_on.13.aspx
Rathore M, Pharmscitech DMA, 2006 undefined. Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops. Springer; Available from: https://link.springer.com/article/10.1208/pt070357 https://doi.org/10.1208/pt070357
Qi H, Gao X, Zhang L, Wei S, … SBE journal of, 2013 undefined. In vitro evaluation of enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0014299913001362
Tegtmeyer S, … IPE journal of, 2001 undefined. Reconstruction of an in vitro cornea and its use for drug permeation studies from different formulations containing pilocarpine hydrochloride. Elsevier [Internet]. [cited 2023 May 20]; Available from: https://www.sciencedirect.com/science/article/pii/S0939641101001230
Reichl S, … JBB journal of, 2004 undefined. Human corneal equivalent as cell culture model for in vitro drug permeation studies. bjo.bmj.com 2004; 88:560-5. Available from: https://bjo.bmj.com/content/88/4/560.short https://doi.org/10.1136/bjo.2003.028225
Valls R, Vega E, Garcia M, … MET open medicinal, 2008 undefined. Transcorneal permeation in a corneal device of non-steroidal anti-inflammatory drugs in drug delivery systems. ncbi.nlm.nih.gov; Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709474/ https://doi.org/10.2174/1874104500802010066
Reichl S, Döhring S, … JBE journal of, 2005 undefined. Human cornea construct HCC-An alternative for in vitro permeation studies? A comparison with human donor corneas. Elsevier; Available from: https://www.sciencedirect.com/science/article/pii/S0939641105000135 https://doi.org/10.1016/j.ejpb.2004.09.016
Rathore MS, Majumdar DK. Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops. AAPS PharmSciTech. 2006 Sep 1; 7(3):E12-7. https://doi.org/10.1208/pt070357
Mojtaba T, Reza GH, Borzo S, Shiva N, Esmaeil S. In vitro antibacterial and antifungal activity of salvia multicaulis. Journal of Essential Oil-Bearing Plants. 2011; 14(2):255-9.
https://doi.org/10.1080/0972060X.2011.10643930
Kaya M, Yıldırır Y, Journal GÇPC, 2015 undefined. Synthesis, Characterization, and In Vitro Antimicrobial and Antifungal Activity of Novel Acridines. Springer. 2015; 48(11):722-6. Available from: https://link.springer.com/article/10.1007/s11094-015-1181-4 https://doi.org/10.1007/s11094-015-1181-4
ophthalmology NRC, 2014 undefined. The impact of timolol maleate on the ocular tolerability of fixed-combination glaucoma therapies. Taylor & Francis. 2014; 8:2541-9. Available from: https://www.tandfonline.com/doi/abs/10.2147/OPTH.S76053 https://doi.org/10.2147/OPTH.S76053
Lin L, Zhao YJ, Chew PTK, Sng CCA, Wong HT, Yip LW, et al. Comparative Efficacy and Tolerability of Topical Prostaglandin Analogues for Primary Open-Angle Glaucoma and Ocular Hypertension. Annals of Pharmacotherapy. 2014 Dec 26; 48(12):1585-93. https://doi.org/10.1177/1060028014548569
Nguyen QD, Ibrahim MA, Watters A, Bittencourt M, Yohannan J, Sepah YJ, et al. Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: Primary 6-month results of the SAVE Study. J Ophthalmic Inflamm Infect. 2013; 3(1):1-15. https://doi.org/10.1186/1869-5760-3-32
Chetoni P, Panichi L, Burgalassi S, Benelli U, Saettone MF. Pharmacokinetics and anti-inflammatory activity in rabbits of a novel indomethacin ophthalmic solution. Journal of Ocular Pharmacology and Therapeutics. 2000; 16(4):363-72. https://doi.org/10.1089/jop.2000.16.363
Li H, Dai M, medica WJP, 2008 undefined. Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity. thieme-connect.com Available from: https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0028-1088332 https://doi.org/10.1055/s-0028-1088332
Chetoni P, Panichi L, … SBJ of ocular, 2000 undefined. Pharmacokinetics and anti-inflammatory activity in rabbits of a novel indomethacin ophthalmic solution. liebertpub.com; Available from: https://www.liebertpub.com/doi/abs/10.1089/jop.2000.16.363 https://doi.org/10.1089/jop.2000.16.363
Kong L, Luo C, Li X, Zhou Y, He H. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipids Health Dis. 2013; 12(1). https://doi.org/10.1186/1476-511X-12-115
Liles JH, Flecknell PA. The use of non-steroidal anti-inflammatory drugs for the relief of pain in laboratory rodents and rabbits. Lab Anim. 1992 Oct 1; 26(4):241-55. https://doi.org/10.1258/002367792780745706
Li H, Dai M, Jia W. Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity. Planta Med. 2009 Jan; 75(1):7-11. https://doi.org/10.1055/s-0028-1088332
Guan J, Zhang Y, Liu Q, Zhang X, PharmSciTech RCA, 2017 undefined. Exploration of alginates as potential stabilizers of nanosuspension. Springer, 2019; 18(8):3172-81. Available from: https://link.springer.com/article/10.1208/s12249-017-0801-6 https://doi.org/10.1208/s12249-017-0801-6
Jacobs C, Müller RH. Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharm Res. 2002; 19(2):189-94. https://doi.org/10.1023/A:1014276917363
Bujňáková Z, Dutková E, Baláž M, … ETIJ of, 2015 undefined. Stability studies of As4S4 nanosuspension prepared by wet milling in Poloxamer 407. Elsevier. Available from: https://www.sciencedirect.com/science/article/pii/S0378517314008552 https://doi.org/10.1016/j.ijpharm.2014.11.043
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