Login Register Cart 0
Generic placeholder image

Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Development and Evaluation of Linalool-loaded Liposomal Gel for Oral Candida Infections: Characterization, Skin Permeation, Dermal Retention, and In Vitro Anti-microbial Studies

Author(s): Vineet Kumar Rai*, Pragati Thakran, Tushar Kanti Rajwar, Alok Sharma, Kuldeep Singh Yadav, Biswakanth Kar, Goutam Ghosh and Goutam Rath

Volume 21, Issue 5, 2023

Published on: 11 September, 2023

Article ID: e090823219593 Pages: 11

DOI: 10.2174/2211352521666230809144537

Price: $65

Abstract

Background: Linalool is a known anti-fungal molecule. It could be a good candidate against oropharyngeal candidiasis if its retention in deeper skin layers, specifically at body temperature, can be extended for a long duration.

Aim: We aimed to develop and evaluate a linalool liposome-based mucoadhesive gel.

Objective: The objective of this study is to improvise localization in oral mucosa by achieving sustained release, ensuring less volatility of linalool and less permeability into the systemic circulation through the mucosa.

Methods: The liposomes were prepared by film formation and hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and morphological characteristics. The lipid carriers were dispersed into the gel matrix of carbopol 934 and HPMC.

Results: The gel was characterized and evaluated for in vitro drug release, ex vivo drug permeation through the goat mucosa and ex vivo dermal retention studies. The particle size and entrapment efficiency were 201 nm and 79.8%, respectively, with 0.300 PDI. Transmission Electron Microscopy revealed the spherical shape of the particles with a well-identified surface. The gel pH (6.8) was close to oral mucosal pH and had desired adhesiveness and rheological properties. The latter portrayed a slow linalool release (74.75% in 12 hours), low permeation (28.80% in 24 hours) through the mucosa and high retention (45%) compared to simple linalool gel, ensuring its improvised anti-microbial effectiveness against Candida.

Conclusion: A mucoadhesive liposomal gel offers a suitable medium for ensuring modified release, improved mucosal retention, and the ability to achieve the desired therapeutic effectiveness locally in mucosa for other drugs of volatile nature.

Graphical Abstract

[1]
Jabra-Rizk, M.A.; Kong, E.F.; Tsui, C.; Nguyen, M.H.; Clancy, C.J.; Fidel, P.L., Jr; Noverr, M. Candida albicans pathogenesis: Fitting within the host-microbe damage response framework. Infect. Immun., 2016, 84(10), 2724-2739.
[http://dx.doi.org/10.1128/IAI.00469-16] [PMID: 27430274]
[2]
Garcia-Cuesta, C.; Sarrion-Pérez, M.G.; Bagán, J.V. Current treatment of oral candidiasis: A literature review. J. Clin. Exp. Dent., 2014, 6(5), e576-e582.
[http://dx.doi.org/10.4317/jced.51798] [PMID: 25674329]
[3]
Wisplinghoff, H.; Ebbers, J.; Geurtz, L.; Stefanik, D.; Major, Y.; Edmond, M.B.; Wenzel, R.P.; Seifert, H. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int. J. Antimicrob. Agents, 2014, 43(1), 78-81.
[http://dx.doi.org/10.1016/j.ijantimicag.2013.09.005] [PMID: 24182454]
[4]
Zida, A.; Bamba, S.; Yacouba, A.; Ouedraogo-Traore, R.; Guiguemdé, R.T. Anti- Candida albicans natural products, sources of new anti-fungal drugs: A review. J. Mycol. Med., 2017, 27(1), 1-19.
[http://dx.doi.org/10.1016/j.mycmed.2016.10.002] [PMID: 27842800]
[5]
Muhammad, I.; Muhammad Ali, S.; Saqib, A.; Amjad, H. Biological importance of essential oils. In: Essential Oils - Oils of Nature; IntechOpen: Rijeka, 2019.
[6]
Quinto, E.J.; Caro, I.; Villalobos-Delgado, L.H.; Mateo, J.; De-Mateo-Silleras, B.; Redondo-Del-Río, M.P. Food safety through natural antimicrobials. Antibiotics, 2019, 8(4), 208.
[http://dx.doi.org/10.3390/antibiotics8040208]
[7]
Morais-Braga, M.F.B.; Sales, D.L.; Carneiro, J.N.P.; Machado, A.J.T.; dos Santos, A.T.L.; de Freitas, M.A.; Martins, G.M.A.B.; Leite, N.F.; de Matos, Y.M.L.S.; Tintino, S.R.; Souza, D.S.L.; Menezes, I.R.A.; Ribeiro-Filho, J.; Costa, J.G.M.; Coutinho, H.D.M. Psidium guajava L. and Psidium brownianum Mart ex DC.: Chemical composition and anti – Candida effect in association with fluconazole. Microb. Pathog., 2016, 95, 200-207.
[http://dx.doi.org/10.1016/j.micpath.2016.04.013] [PMID: 27085299]
[8]
Slimen, S.; Kais, R.; Karim, H.; Hichem, S. Essential oil, chemical compositions, and therapeutic potential. In: Essential Oils; IntechOpen: Rijeka, 2022.
[9]
Shreaz, S.; Wani, W.A.; Behbehani, J.M.; Raja, V.; Irshad, M.; Karched, M.; Ali, I.; Siddiqi, W.A.; Hun, L.T. Cinnamaldehyde and its derivatives, a novel class of antifungal agents. Fitoterapia, 2016, 112, 116-131.
[http://dx.doi.org/10.1016/j.fitote.2016.05.016] [PMID: 27259370]
[10]
Rajkowska, K.; Nowak, A.; Kunicka-Styczyńska, A.; Siadura, A. Biological effects of various chemically characterized essential oils: investigation of the mode of action against Candida albicans and HeLa cells. RSC Advances, 2016, 6(99), 97199-97207.
[http://dx.doi.org/10.1039/C6RA21108A]
[11]
Mani-López, E.; Cortés-Zavaleta, O.; López-Malo, A. A review of the methods used to determine the target site or the mechanism of action of essential oils and their components against fungi. SN Applied Sciences, 2021, 3(1), 44.
[http://dx.doi.org/10.1007/s42452-020-04102-1]
[12]
Singh, S.; Fatima, Z.; Hameed, S. Citronellal-induced disruption of membrane homeostasis in Candida albicans and attenuation of its virulence attributes. Rev. Soc. Bras. Med. Trop., 2016, 49(4), 465-472.
[http://dx.doi.org/10.1590/0037-8682-0190-2016] [PMID: 27598633]
[13]
Guo, F.; Chen, Q.; Liang, Q.; Zhang, M.; Chen, W.; Chen, H. Antimicrobial activity and proposed action mechanism of linalool against pseudomonas fluorescens. Front. Microbiol., 2021, 12, 562094.
[http://dx.doi.org/10.3389/fmicb.2021.562094]
[14]
Afshar, M.; Najafian, S.; Radi, M. The effect of harvest time on the natural product of Rosmarinus officinalis L. from South Iran (Fars province). Nat. Prod. Res., 2022, 36(10), 2637-2642.
[http://dx.doi.org/10.1080/14786419.2021.1914615] [PMID: 33974457]
[15]
Lin, L.Y.; Peng, C.C.; Wang, H.E.; Liu, Y.W.; Shen, K.H.; Chen, K.C.; Peng, R.Y. Active volatile constituents in Perilla frutescens essential oils and improvement of antimicrobial and anti-inflammatory bioactivity by fractionation. J. Essent. Oil-Bear. Plants, 2016, 19(8), 1957-1983.
[http://dx.doi.org/10.1080/0972060X.2016.1226962]
[16]
Perry, S.L.; McClements, D.J. Recent advances in encapsulation, protection, and oral delivery of bioactive proteins and peptides using colloidal systems. Molecules, 2020, 25(5), 1161.
[17]
Al-Remawi, M.; Elsayed, A.; Maghrabi, I.; Hamaidi, M.; Jaber, N. Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system. Pharm. Dev. Technol., 2017, 22(3), 390-398.
[http://dx.doi.org/10.1080/10837450.2016.1213745] [PMID: 27470482]
[18]
Lee, M-K. Liposomes for enhanced bioavailability of water-insoluble drugs: In vivo evidence and recent approaches. Pharmaceutics, 2020, 12(3), 264.
[19]
He, H.; Lu, Y.; Qi, J.; Zhu, Q.; Chen, Z.; Wu, W. Adapting liposomes for oral drug delivery. Acta Pharm. Sin. B, 2019, 9(1), 36-48.
[http://dx.doi.org/10.1016/j.apsb.2018.06.005] [PMID: 30766776]
[20]
Hammoud, Z.; Gharib, R.; Fourmentin, S.; Elaissari, A.; Greige-Gerges, H. New findings on the incorporation of essential oil components into liposomes composed of lipoid S100 and cholesterol. Int. J. Pharm., 2019, 561, 161-170.
[http://dx.doi.org/10.1016/j.ijpharm.2019.02.022] [PMID: 30836153]
[21]
Coimbra, M.; Isacchi, B.; van Bloois, L.; Torano, J.S.; Ket, A.; Wu, X.; Broere, F.; Metselaar, J.M.; Rijcken, C.J.F.; Storm, G.; Bilia, R.; Schiffelers, R.M. Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. Int. J. Pharm., 2011, 416(2), 433-442.
[http://dx.doi.org/10.1016/j.ijpharm.2011.01.056] [PMID: 21291975]
[22]
Sherry, M.; Charcosset, C.; Fessi, H.; Greige-Gerges, H. Essential oils encapsulated in liposomes: A review. J. Liposome Res., 2013, 23(4), 268-275.
[http://dx.doi.org/10.3109/08982104.2013.819888] [PMID: 23879218]
[23]
Ruozi, B.; Tosi, G.; Forni, F.; Angela Vandelli, M. Ketorolac tromethamine liposomes: Encapsulation and release studies. J. Liposome Res., 2005, 15(3-4), 175-185.
[http://dx.doi.org/10.1080/08982100500364214] [PMID: 16393909]
[24]
Zhang, X.; Liu, J.; Qiao, H.; Liu, H.; Ni, J.; Zhang, W.; Shi, Y. Formulation optimization of dihydroartemisinin nanostructured lipid carrier using response surface methodology. Powder Technol., 2010, 197(1-2), 120-128.
[http://dx.doi.org/10.1016/j.powtec.2009.09.004]
[25]
Liu, C.H.; Wu, C.T. Optimization of nanostructured lipid carriers for lutein delivery. Colloids Surf. A Physicochem. Eng. Asp., 2010, 353(2-3), 149-156.
[http://dx.doi.org/10.1016/j.colsurfa.2009.11.006]
[26]
Jin, B.S.; Lee, S.M.; Lee, K.H. A study on the factors affecting entrapment efficiency and particle size of ethosomes. Appl. Chem. Eng., 2006, 17(2), 138-143.
[27]
Rai, V.K.; Yadav, N.P.; Sinha, P.; Mishra, N.; Luqman, S.; Dwivedi, H.; Kymonil, K.M.; Saraf, S.A. Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery. Carbohydr. Polym., 2014, 103, 126-133.
[http://dx.doi.org/10.1016/j.carbpol.2013.12.019] [PMID: 24528709]
[28]
Upadhyay, D.K.; Sharma, A.; Kaur, N.; Gupta, G.D.; Narang, R.K.; Rai, V.K. Nanoemulgel for efficient topical delivery of finasteride against androgenic alopecia. J. Pharm. Innov., 2021, 16(4), 735-746.
[http://dx.doi.org/10.1007/s12247-020-09483-9]
[29]
aTomić, I.; Juretić, M.; Jug, M.; Pepić, I.; Cetina Čižmek, B.; Filipović-Grčić, J. Preparation of in situ hydrogels loaded with azelaic acid nanocrystals and their dermal application performance study. Int. J. Pharm., 2019, 563, 249-258.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.016] [PMID: 30965120]
[30]
Sharma, A.; Upadhyay, D.K.; Sarma, G.S.; Kaur, N.; Gupta, G.D.; Narang, R.K.; Rai, V.K. Squalene integrated NLC based gel of tamoxifen citrate for efficient treatment of psoriasis: A preclinical investigation. J. Drug Deliv. Sci. Technol., 2020, 56, 101568.
[http://dx.doi.org/10.1016/j.jddst.2020.101568]
[31]
Negi, P.; Sharma, I.; Hemrajani, C.; Rathore, C.; Bisht, A.; Raza, K.; Katare, O.P. Thymoquinone-loaded lipid vesicles: A promising nano-medicine for psoriasis. BMC Complement. Altern. Med., 2019, 19(1), 334.
[http://dx.doi.org/10.1186/s12906-019-2675-5] [PMID: 31771651]
[32]
Srivastava, N.; Patel, D.K.; Rai, V.K.; Pal, A.; Yadav, N.P. Development of emulgel formulation for vaginal candidiasis: Pharmaceutical characterization, in vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol., 2018, 48, 490-498.
[http://dx.doi.org/10.1016/j.jddst.2018.10.013]
[33]
Saha, I.; Palak, A.; Rai, V.K. Relevance of NLC-gel and microneedling-assisted tacrolimus ointment against severe psoriasiform: in vitro dermal retention kinetics, in vivo activity and drug distribution. J. Drug Deliv. Sci. Technol., 2022, 71, 103272.
[http://dx.doi.org/10.1016/j.jddst.2022.103272]
[34]
Moghimipour, E.; Aghel, N.; Zarei Mahmoudabadi, A.; Ramezani, Z.; Handali, S. Preparation and characterization of liposomes containing essential oil of eucalyptus camaldulensis leaf. Jundishapur J. Nat. Pharm. Prod., 2012, 7(3), 117-122.
[http://dx.doi.org/10.17795/jjnpp-5261] [PMID: 24624167]
[35]
Dias, I.J.; Trajano, E.; Castro, R.D.; Ferreira, G.L.S.; Medeiros, H.C.M.; Gomes, D.Q.C. Antifungal activity of linalool in cases of Candida spp. isolated from individuals with oral candidiasis. Braz. J. Biol., 2018, 78(2), 368-374.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy