Enhanced skin localization of doxycycline using microparticles and hydrogel: effect of oleic acid as penetration enhancer
DOI:
https://doi.org/10.12928/pharmaciana.v11i2.21044Keywords:
Oleic acid, gel, doxycycline microparticle, penetration enhancerAbstract
One of the disadvantages of gel preparations is the poor ability to penetrate the skin. Herein we developed a sodium carboxymethylcellulose (NaCMC)-based gel containing microparticle of doxycycline hyclate (DOX). Oleic acid (OA) was added into the gel formulation specifically to increase the penetrability of DOX microparticles. The objective of this work was to determine the effect of varying concentration of OA on the physical characteristics, penetration and retention abilities of DOX. DOX microparticles were initially prepared using PLGA as a matrix and then incorporated into a NaCMC-based gel with various OA concentrations: 0%, 2.5%, 5%, 7.5%, and 10% for F1, F2, F3, F4, and F5, respectively. The gel preparations were evaluated for their organoleptic test, homogeneity, pH measurement, viscosity, spreadability, as well as ex vivo penetration and retention abilities. The physical characteristics tests revealed a homogeneous yellow gel with a distinctive odor and pH values compatible with the pH requirements of human skin. The retention test showed the formulation retained 1236.46 µg of DOX in the skin. Finally, the skin retention of DOX from microparticles loaded gel was significantly higher compared to the free DOX loaded gel, indicating the microparticles can be extremely effective in retaining the DOX in the infected area.
References
Adib, Z. M., Ghanbarzadeh, S., Kouhsoltani, M., Khosroshahi, A. Y., & Hamishehkar, H. (2016). The effect of particle size on the deposition of solid lipid nanoparticles in different skin layers: A histological study. Advanced Pharmaceutical Bulletin, 6(1), 31–36. https://doi.org/doi.org/10.15171/apb.2016.006
Akalin, G. O., & Pulat, M. (2018). Preparation and characterization of nanoporous sodium carboxymethyl cellulose hydrogel beads. Journal of Nanomaterials, Article ID. https://doi.org/https://doi.org/10.1155/2018/9676949
Ali, S. M., & Yosipovitch, G. (2013). Skin pH: From basic science to basic skin care. In Acta Dermato-Venereologica. Acta Derm Venereol, 93(3), 261–267. https://doi.org/https://doi.org/10.2340/00015555-1531
Ardana, M., Aeyni, V., & Ibrahim, A. (2015). Formulasi dan optimasi basis gel HPMC (Hidroxy Propyl Methyl Cellulose) dengan berbagai variasi konsentrasi. Journal of Tropical Pharmacy and Chemistry, 3(2), 101–108. https://doi.org/https://doi.org/10.25026/jtpc.v3i2.95
Banning, T. P., & Heard, C. M. (2002). Binding of doxycycline to keratin, melanin and human epidermal tissue. International Journal of Pharmaceutics, 235((1–2)), 219–227. https://doi.org/10.1016/s0378-5173(01)00988-7
Borse, V. A., & Avinash Balasaheb Gangude Anil Bhavrao Deore. (2020). Formulation and evaluation of antibacterial topical gel of doxycycline hyclate, neem oil and tea tree oil. Indian Journal of Pharmaceutical Education and Research, 54((1)), 206–212. https://doi.org/10.5530/ijper.54.1.24
Campos, E., Branquinho, J., Carreira, A. S., Carvalho, A., Coimbra, P., Ferreira, P., & Gil, M. H. (2013). Designing polymeric microparticles for biomedical and industrial applications. European Polymer Journal, 49(8), 2005–2021. https://doi.org/10.1016/j.eurpolymj.2013.04.033
Chiller, K., Selkin, B. A., & Murakawa, G. J. (2001). Skin microflora and bacterial infections of the skin. Journal of Investigative Dermatology Symposium Proceedings, 6((3)), 170–174. https://doi.org/10.1046/j.0022-202x.2001.00043.x
Chukwudi, C. U. (2016). rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrobial Agents and Chemotherapy, 60(8), 4433–4441. https://doi.org/10.1128/AAC.00594-16
Cohen-Sela, E., Chorny, M., Koroukhov, N., & Golomb, H. D. D. G. (2009). A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. Journal of Controlled Release, 133 (2), 90–95. https://doi.org/10.1016/j.jconrel.2008.09.073
Nandini, D,. NS, Chauhan., & K, Chandra. A., Pathak. (2009). Effect of permeation enhancers on the release and permeation kinetics of oxytetracycline hydrochloride organogel formulations. Journal of Young Pharmacists, 1((4)), 296–300. https://doi.org/10.4103/0975-1483.59314
Dian Permana, A., Nurul Utami, R., J.Courtenay, A., A.Manggau, M., F.Donnelly, R., & Rahman, L. (2020). Phytosomal nanocarriers as platforms for improved delivery of natural antioxidant and photoprotective compounds in propolis: An approach for enhanced both dissolution behaviour in biorelevant media and skin retention profiles. Journal of Photochemistry and Photobiology B: Biology, 205(111846). https://doi.org/10.1016/j.jphotobiol.2020.111846
Elisa Campos, J.Branquinho, S.Carreira, A., Carvalho, A., Coimbra, P., & P.FerreiraM.H.Gil. (2013). Designing polymeric microparticles for biomedical and industrial applications. European Polymer Journal, 49((8)), 2005–2021. https://doi.org/10.1016/j.eurpolymj.2013.04.033
Han, F. Y., Thurecht, K. J., Whittaker, A. K., & Smith, M. T. (2016). Bioerodable PLGA-based microparticles for producing sustained-release drug formulations and strategies for improving drug loading. Frontiers in Pharmacology, 7(185), 1–11. https://doi.org/10.3389/fphar.2016.00185
J.Hatlen, T., & G.Miller, L. (2021). Staphylococcal skin and soft tissue infections. Infectious Disease Clinics of North America, 35(1), 81–105. https://doi.org/10.1016/j.idc.2020.10.003
Kalan, C., & Femling, J. (2017). Skin and soft tissue infections: causes and treatments. Physician Assistant Clinics, 2(3), 421–433. https://doi.org/10.1016/j.cpha.2017.02.006
Kim, Y., Beck-Broichsitter, M., & Banga, A. K. (2019). Design and evaluation of a poly(Lactide-co-glycolide)-based in situ film-forming system for topical delivery of trolamine salicylate. Pharmaceutics, 11(8). https://doi.org/10.3390/pharmaceutics11080409
Lengyel, M., Kállai-Szabó, N., Antal, V., Laki, A. J., & Antal, I. (2019). Microparticles, microspheres, and microcapsules for advanced drug delivery. Scientia Pharmaceutica, 87(3), 1–31. https://doi.org/10.3390/scipharm87030020
Lopez, C. G., Colby, R. H., & Cabral, J. T. (2018). Electrostatic and hydrophobic interactions in NaCMC aqueous solutions: effect of degree of substitution. Polyelectrolyte Structure, Dynamics and Solution Rheology, 1–22. https://doi.org/10.1021/acs.macromol.8b00178
Machado, H. A., Abercrombie, J. J., You, T., DeLuca, P. P., & Leung, K. P. (2013). Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel. BioMed Research International, Article ID, 1–11. https://doi.org/10.1155/2013/387863
Marco, D. B. A. De, Giuffrida, R., Conforti, C., Barlusconi, C., Foti, C., & Romita, P. (2020). Topical antibiotics in the dermatological clinical practice: Indications, efficacy, and adverse effects. Dermatologic Therapy, 33((6):e13824). https://doi.org/10.1111/dth.13824
Mazzara, J. M., Ochyl, L. J., Hong, J. K. Y., Moon, J. J., Prausnitz, M. R., & Schwendeman P, S. (2019). Self-healing encapsulation and controlled release of vaccine antigens from PLGA microparticles delivered by microneedle patches. Bioeng Transl Med, 4((1)), 116–128. https://doi.org/10.1002/btm2.10103
Nitalikar, M. M., & Sakarkar, D. M. (2013). Formulation and evaluation of topical gel of Meloxicam with Beta-Cyclodextrin complex. Research Journal of Pharmacy and Technology, 6((7)), 790–793
Patil, P. B., Datir, S. K., & Saudagar, R. B. (2019). A review on topical gels as drug delivery system. Journal of Drug Delivery and Therapeutics, 9(3–(s)), 989–994. https://doi.org//10.22270/jddt.v9i3-s.2930
Permana, A. D., Mir, M., Utomo, E., & F.Donnelly, R. (2020). Bacterially sensitive nanoparticle-based dissolving microneedles of doxycycline for enhanced treatment of bacterial biofilm skin infection: A proof of concept study. International Journal of Pharmaceutics: X, 2(100047). https://doi.org/10.1016/j.ijpx.2020.100047
Prakash, D., Singh, A. P., Katiyar, N. S., & Pathak, K. (2016). Penetration enhancers: adjuvants in transdermal drug delivery system. World Journal of Pharmacy and Pharmaceutical Sciences, 5((5)), 353–376. https://doi.org/10.20959/wjpps20165-6654
Prow, T. W., Grice, J. E., Lin, L. L., Faye, R., Butler, M., Becker, W., … Roberts, M. S. (2011). Nanoparticles and microparticles for skin drug delivery. Advanced Drug Delivery Reviews, 63(6), 470–491. https://doi.org/10.1016/j.addr.2011.01.012
Purnamawati, S., Indrastuti, N., Danarti, R., & Saefudin, T. (2017). The role of moisturizers in addressing various kinds of dermatitis: A review. In Clinical Medicine and Research (Vol. 15, Issues 3–4, pp. 75–87). Marshfield Clinic. https://doi.org/10.3121/cmr.2017.1363
Santoyo, S., & Gartua, P. Y. (2000). Effect of skin pretreatment with fatty acids on percutaneous absorption and skin retention of piroxicam after its topical application. European Journal of Pharmaceutics and Biopharmaceutics, 50(2), 245–250. https://doi.org/10.1016/S0939-6411(00)00097-7
Singh Malik, D., & Kaur, G. (2018). Nanostructured gel for topical delivery of azelaic acid: Designing, characterization, and in-vitro evaluation. Journal of Drug Delivery Science and Technology, 47, 123–136. https://doi.org/10.1016/j.jddst.2018.07.008
Smith, R., Russo, J., Fiegel, J., & Brogden, N. (2020). Antibiotic delivery strategies to treat skin infections when innate antimicrobial defense fails. Antibiotics, 9(2), 56. https://doi.org/10.3390/antibiotics9020056
Soomherun, N., Kreua-ongarjnukool, N., Chumnanvej, S., & Thumsing, S. (2017). Encapsulation of nicardipine hydrochloride and release from biodegradable poly(D,L-lactic-co-glycolic acid) microparticles by double emulsion process: effect of emulsion stability and different parameters on drug entrapment. International Journal of Biomaterials, Article ID, 1–13. https://doi.org/10.1155/2017/1743765
Souto, E. B., Wissing, S. A., Barbosa, C. M., & Müller, R. H. (2004). Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. European Journal of Pharmaceutics and Biopharmaceutics, 58((1)), 83–90. https://doi.org/10.1016/j.ejpb.2004.02.015
Wavikar, P., & Vavia, P. (2013). Nanolipidgel for enhanced skin deposition and improved antifungal activity. AAPS PharmSciTech, 14((1)), 222–233. https://doi.org/10.1208/s12249-012-9908-y
Wohlrab, J., & Gebert, A. (2018). PH and Buffer Capacity of Topical Formulations. Current Problems in Dermatology (Switzerland), 54, 123–131. https://doi.org/10.1159/000489526
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