Abstract
This study aimed (i) to prepare liquid crystalline systems (LCS) of glyceryl monooleate (GMO) and water containing antibacterial compounds and (ii) to evaluate their potential as drug delivery systems for topical treatment of bacterial infections. Therefore, LCS containing CPC (cetylpyridinium chloride) (LCS/CPC) and PHMB (poly(hexamethylene biguanide) hydrochloride) (LCS/PHMB) were prepared and the liquid crystalline phases were identified by polarizing light microscopy 24 h and 7 days after preparation. The in vitro drug release profile and in vitro antibacterial activity of the systems were assessed using the double layer agar diffusion method against Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Escherichia coli, and Enterococcus faecalis. The interaction between GMO and the drugs was evaluated by a drug absorption study. Stable liquid crystalline systems containing CPC and PHMB were obtained. LCS/PHMB decreased the PHMB release rate and exerted strong antibacterial activity against all the investigated bacteria. In contrast, CPC interacted with GMO so strongly that it became attached to the system; the amount released was not sufficient to exert antibacterial activity. Therefore, the studied liquid crystalline systems were suitable to deliver PHMB, but not CPC. Accordingly, it was demonstrated that GMO interacts with each drug differently, which may interfere in the final efficiency of GMO/water LCS.
Similar content being viewed by others
References
Sanchez DA, Nosanchuk JD, Friedman AJ. The skin microbiome: is there a role in the pathogenesis of atopic dermatitis and psoriasis? J Drugs Dermatol. 2015;14(2):127–30.
Weyrich LS, Dixit S, Farrer AG, Cooper AJ, Cooper AJ. The skin microbiome: associations between altered microbial communities and disease. Australas J Dermatol. 2015;56(4):268–74. doi:10.1111/ajd.12253.
Ulmer M, Patzelt A, Vergou T, Richter H, Müller G, et al. In vivo investigation of the efficiency of a nanoparticle-emulsion containing polihexanide on the human skin. Eur J Pharm Biopharm. 2013;84:325–9.
Friedman M, Harrari D, Rimer A, Stabholz A. Inhibition of plaque formation by a sustained release delivery system for cetylpyridinium chloride. Int J Pharm. 1988;44:243–7.
Norling T, Lading P, Engstron S, Larsson K, Krog N, et al. Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease. J Clin Periodontol. 1992;19:687–92.
Farkas E, Kiss D, Zelkó R. Study on the release of chlorhexidine base and salts from different liquid crystalline structures. Int J Pharm. 2007;340:71–5.
Muller G, Koburger T, Kramer A. Interaction of polyhexamethylene biguanide hydrochloride (PHMB) with phosphatidylcholine containing o/w emulsion and consequences for microbial efficacy and cytotoxicity. Chem Biol Interact. 2013;201:58–64.
Finger S, Wiegand C, Buschmann HJ, Hipler UC. Antibacterial properties of cyclodextrin–antiseptics-complexes determined by microplate laser nephelometry and ATP bioluminescence assay. Int J Pharm. 2013;452:188–93.
Tyle P. Liquid crystal and their application in drug delivery. In: Rosoff M, editor. Controlled release of drug: polymers and aggregate systems. New York: Morton Rosoff UHC Publishers; 1989. p. 125–62.
Guo C, Wang J, Cao F, Lee RJ, Zhai G. Lyotropic liquid crystal systems in drug delivery. Drug Discov Today. 2010;15:1032–40.
Phan S, Fong WK, Kirby N, Hanley T, Boyd BJ. Evaluation the link between self-assembled mesophase structure and drug release. Int J Pharm. 2011;421:176–82.
Shah JC, Sadhala Y, Chilukuri DM. Cubic phase as drug delivery systems. Adv Drug Del Rev. 2001;47:229–50.
Boyd BJ, Whittaker DV, Khoo S, Davey G. Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int J Pharm. 2006;309:218–26.
Rizwan SB, Hanley T, Boyd BJ, Rades T, Hook S. Liquid crystalline systems of phytantriol and glyceryl monooleate containing a hydrophilic protein: characterisation, swelling and release kinetics. J Pharm Sci. 2009;98:4191–204.
Freag MS, Elnaggar YSR, Abdelmonsif DA, Abdallah OY. Stealth, biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells: in vitro and in vivo studies. Int J Nanomedicine. 2016;2016(11):4799–818.
Depieri LV, Borgheti-Cardoso LN, Campos PM, Otaguiri KK, Vicentini FTMC, Lopes LB, et al. RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase. Eur J Pharma Biopharm. 2016;105:50–8.
Fonseca-Santos B, dos Santos AM, Rodero CF, Gremião MPD, Chorilli M. Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery. Int J Nanomedicine. 2016;2016(11):4553–62.
Leaper DJ, Schultz G, Carville K, Fletcher J, Swanson T, Drake R. Extending the TIME concept: what have we learned in the past 10 years? Int Wound J. 2012;9(2):1–19. doi:10.1111/j.1742-481X.2012.01097.x.
Souza C, Watanabe E, Borgheti-Cardoso LN, Fantini MCA, Lara MG. Mucoadhesive system formed by liquid crystals for buccal administration of poly(hexamethylene biguanide) hydrochloride. J Pharm Sci. 2014;103:3914–23.
Yang SC, Aljuffali IA, Sung CT, Lin CF, Fang JY. Antimicrobial activity of topically-applied soyaethyl morpholinium ethosulfate micelles against Staphylococcus species. Nanomedicine (London). 2016;11(6):657–71. doi:10.2217/nnm.15.217.
Milak S, Zimmer A. Glycerol monooleate liquid crystalline phases used in drug delivery systems. Int J Pharm. 2015;478:569–87.
Sallam A-S, Hamudi FF, Khalil EA. Effect of ethylcellulose and propylene glycol on the controlled-release performance of glyceryl monooleate-mertronidazole periodontal gel. Pharm Dev Technol. 2015;20(2):159–68. doi:10.3109/10837450.2013.852573.
Esposito E, Carotta V, Scabbia A, Trombelli L, D’Antona P, Menegatti E, et al. Comparative analysis of tetracycline-containing dental gels: poloxamer- and monoglyceride-based formulations. Int J Pharm. 1996;142(1):9–23. doi:10.1016/0378-5173(96)04649-2.
Boge L, Bysell H, Ringstad L, Wennman D, Umerska A, et al. Lipid-based liquid crystals as carriers for antimicrobial peptides: phase behavior and antimicrobial effect. Langmuir. 2016;32(17):4217–28. doi:10.1021/acs.langmuir.6b00338.
Engstrom S, Larsson K, Lindman B. Liquid crystalline phases as delivery systems for drugs: I. Basic principles. Control Release Bioac Mater. 1988;105.
Rosevear FB. The microscopy of the liquid crystalline neat and middle phases of soaps and synthetic detergents. J Am Chem Soc. 1954;31:628–39.
Victorino FR, Bramante CM, Watanabe E, Ito IT, Franco SL, et al. Antibacterial activity of propolis-based toothpastes for endodontic treatment. Braz J Pharm Sci. 2009;45:795–800.
Pires de Souza FC, Moraes PC, Garcia LF, Aguilar FG, Watanabe E. Evaluation of pH, calcium ion release and antimicrobial activity of a new calcium aluminate cement. Braz Oral Res. 2013;27:324–30.
Higuchi WI. Analysis of data on the medicament release from ointments. J Pharm Sci. 1962;51:802–4.
Gelfuso GM, Gratieri T, Simão PS, Freitas LAP, Lopez RFV. Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate. J Microencapsul. 2011;28(7):650–8.
Chang CM, Bodmeier R. Binding of drugs to monoglyceride-based drug delivery systems. Int J Pharm. 1997;147:135–42.
Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4):244–53. Erratum in: Nat Rev Microbiol. 2011;9(8):626. doi:10.1038/nrmicro2537.
Owens CD, Stoessel K. Surgical site infections: epidemiology, microbiology and prevention. J Hosp Infect. 2008;70(2):3–10. doi:10.1016/S0195-6701(08)60017-1.
Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005;99:703–15.
Patel R, Patel TN. Liquid crystals and their application in the field of drug delivery. In: Fanun M, editor. Colloid in drug delivery, vol. 150. USA: CRC Press; 2010. p. 311–36.
Chang CM, Bodmeier R. Low viscosity monoglyceride-based drug delivery systems transforming into a highly viscous cubic phase. Int J Pharm. 1998;173:51–60.
Geraghty PB, Attwood D, Collett JH, Dandiker Y. The in vitro release of some muscarinic drugs from monoolein/water lyotropic crystalline gels. Pharm Res. 1996;13:1265–71.
Myhrman E, Hakansson J, Lindgren K, Bjorn C, Sjostrand V, et al. The novel antimicrobial peptide PXL150 in the local treatment of skin and soft tissue infections. Appl Microbiol Biotechnol. 2013;97:3085–96.
Estrela C, Silva JA, de Alencar AH, Leles CR, Decurcio DA. Efficacy of sodium hypochlorite and chlorhexidine against Enterococcus faecalis—a systematic review. J Appl Oral Sci. 2008;16:364–8.
Guerreiro-Tanomaru JM, Chávez-Andrade GM, de Faria-Júnior NB, Watanabe E, Tanomaru-Filho M. Effect of passive ultrasonic irrigation on Enterococcus faecalis from root canals: an ex vivo study. Braz Dent J. 2015;26:342–6.
De Paula GF, Netto GI, Mattoso LHC. Physical and chemical characterization of poly(hexamethylene biguanide) hydrochloride. Polymers. 2011;3:928–41.
Wessels S, Ingmer H. Modes of action of three disinfectant active substances: a review. Regul Toxicol Pharmacol. 2013;67:456–67.
Lee J, Kellaway IW. In vitro peptide release from liquid crystalline buccal delivery systems. Int J Pharm. 2000;195:29–33.
Burrows R, Collett JH, Attwood D. The release of drugs from monoglyceride-water liquid crystalline phases. Int J Pharm. 1994;111:283–93.
Sallam A, Khalil E, Ibrahim H, Freij I. Formulation of an oral dosage form utilizing the properties of cubic liquid crystalline phases of glyceryl monooleate. Eur J Pharm Biopharm. 2002;53:343–52.
Estracanholli EA, Praça FG, Cintra AB, Pierre MBR, Lara MG. Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies. AAPS PharmSciTech. 2014;15(6):1468–75. doi:10.1208/s12249-014-0171-2.
Chang CM, Bodmeier R. Swelling of and drug release from monoglyceride-based drug delivery systems. J Pharm Sci. 1997;86:747–52.
Chang CM, Bodmeier R. Effect of dissolution media and additives on the drug release from cubic phase delivery systems. J Control Release. 1997;46:215–22.
Ganem-Quintanar A, Quintanar-Guerreiro D, Buri P. Monoolein: a review of the pharmaceutical applications. Drug Dev Ind Pharm. 2000;26:809–20.
Acknowledgements
The authors thank the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil) and the National Council for Scientific and Technological Development (CNPq, Brazil) for their financial support to this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Souza, C., Watanabe, E., Aires, C.P. et al. Effect of Liquid Crystalline Systems Containing Antimicrobial Compounds on Infectious Skin Bacteria. AAPS PharmSciTech 18, 2110–2119 (2017). https://doi.org/10.1208/s12249-016-0690-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-016-0690-0