{"id":52119,"date":"2023-09-30T11:34:46","date_gmt":"2023-09-30T11:34:46","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=52119"},"modified":"2023-10-07T08:48:49","modified_gmt":"2023-10-07T08:48:49","slug":"an-in-vitro-evaluation-of-anti-fungal-activity-of-different-nano-forms-of-fluconazole-against-candida-albicans","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no3\/an-in-vitro-evaluation-of-anti-fungal-activity-of-different-nano-forms-of-fluconazole-against-candida-albicans\/","title":{"rendered":"An In Vitro Evaluation of Anti-fungal Activity of Different Nano forms of Fluconazole Against Candida albicans"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Fluconazole is a first-generation triazole antifungal.\nIt is used to treat a wide range of fungal infections. Examples\ninclude Candida, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis\nversicolor. It is also used to prevent candidiasis in a high-risk population, such as those who had organ transplants,\npremature neonates, or have low blood\nneutrophil counts 1<\/sup>.<\/p>\n\n\n\n

Candida albicans <\/em>has historically been the most common species responsible for these\ninfections, and it continues to be a\nprevalent pathogen. However, there are other Candida species, including Candida tropicalis, Candida glabrata,\nCandida krusei, Candida parapsilosis, Candida guilliermondii, and more, which can also cause infections. Each of these species may exhibit different\ncharacteristics, drug susceptibilities, and clinical manifestations. The\nrise in the prevalence of invasive systemic\ncandidiasis, especially in immunocompromised individuals, is concerning. Factors such as the increased use of broad-spectrum\nantibiotics, immunosuppressive therapies, and\nthe growing population of individuals with conditions that weaken the immune\nsystem (e.g., HIV\/AIDS, cancer, organ\ntransplantation) contribute to this trend. Additionally, Candida species can develop resistance to antifungal medications, which further complicates treatment.<\/p>\n\n\n\n

Efforts in healthcare and research are ongoing to better\nunderstand these fungal infections and to develop improved\nstrategies for prevention and treatment. Early diagnosis and appropriate antifungal therapy are crucial for\nmanaging candidiasis and reducing its impact on vulnerable patient\npopulations. This may involve a combination of antifungal drugs, depending on the species\nof Candida involved and their\nsusceptibility to different medications2<\/sup>.<\/p>\n\n\n\n

The increasing number of reports from around the world\nabout drug resistance among fungi and Candida\nspecies, combined with the production of new antifungal drugs, indicates the\nneed for testing susceptibility to\nthese drugs and makes researchers eager to determine susceptibility patterns\nfor the various antifungal drugs1-3<\/sup>. Recently,\nthe synthesis of nanoparticles by microorganisms has been recognized as a viable option for large manufacturing of nanoparticles4,5<\/sup>.\nThese particles are utilized to transport antifungal drugs such as itraconazole6-8.<\/sup> Because of their tiny size, these lipid\nnanoparticles have more access to tissues and have greater effect9-12<\/sup>. These drug delivery\nmethods provide regulated drug release, enhancing the chemical stability of the trapped pharmaceuticals.\nFurthermore, these systems are among the safest and most secure carriers that can be mass-produced on a huge scale13-15<\/sup>. <\/em>The effect of nano agents is compared\nto the regular form of Fluconazole in this study to determine\nthe efficacy and comparability.<\/p>\n\n\n\n

Nanovesicles are widely used to deliver and\/or target active ingredients to different body organs and tissues16<\/sup>. A wide range of developed nanovesicles includes liposomes, niosomes, ethosomes, transfersomes, cubosomes, and micelles17-19<\/sup>. They have been acting as a platform for improving drug solubility, stability, release profile, and bioavailability [20]<\/sup>. These nanovesicles have been optimized to be taken by all routes of administration including oral, buccal, nasal, ocular, transdermal, as well as parenteral routes. Further modifications have been performed to develop vector-oriented nanovesicles for drugs targeting to colon, brain, liver, and tumor 21<\/sup>.<\/p>\n\n\n\n

In the current study, the antifungal activity of\nnano-fluconazole was compared to normal aqueous fluconazole on Candida albicans <\/em>which\nis clinically important\nfungi.<\/p>\n\n\n\n

Material and methods<\/strong><\/p>\n\n\n\n

This research was carried out in microbiology lab at Gulf Medical University, Ajman. It is\nan experimental study that aims to\nemphasise the effect of nano-fluconazole forms on Candida albicans<\/em>. It is a pilot study\nperformed using a control strains of Candida\nalbicans <\/em>ATCC 66027. The institutional IRB approved\nthe study in accordance with the GMU\nresearch policies.<\/p>\n\n\n\n

Procedure of the study<\/strong><\/p>\n\n\n\n

The pellet\nof lyophilized Candida\nis reconstituted as per the instruction of the ATCC.<\/p>\n\n\n\n

Preparation of fluconazole nanovesicles<\/strong><\/p>\n\n\n\n

The nanovesicles were prepared in the college of\nPharmacy at GMU using a modified thin film hydration\ntechnique22<\/sup>. Briefly, fluconazole, cetyl alcohol and Tween 80 were\nprecisely weighed, dissolved in 10 mL\nmixture of methanol: chloroform, in a ratio of 2:1 v\/v, and transferred into\n250 mL round-bottom flask. Under\nvacuum, the organic solvents mixture was evaporated using the rotary evaporator (Rotavapor, Heidolph VV\n2000, Burladingen, Germany) rotating at 150 rpm for 20 min at temperature 60 \u00baC. The wall-assembled thin film has\nbeen hydrated under normal pressure\nusing 10 mL aqueous solution of low molecular weight chitosan in 0.1 M acetic\nacid. Finally, the prepared nanovesicles were sonicated in ultrasonic bath (Model SH 150-41, PCI Analytics Pvt. Ltd, Mumbai, India) for 1 minute\nto avoid aggregation23<\/sup>.<\/p>\n\n\n\n

Statistical Design<\/strong><\/p>\n\n\n\n

Central composite design was utilized to study the\neffect of the formulation variables on the characteristics of prepared nanovesicles using Design-Expert\u00ae<\/sup> 7 software (Version\n7, Stat-Ease Inc., MN). Two independent factors were\nstudied as follows: Tween\/Cetyl ratio (X1) and\nchitosan percentage (X2). The\ntraced responses were the vesicular size (PS, Y1),\npolydispersity index (PDI, Y2), zeta\npotential (ZP, Y3) and encapsulation efficiency (EE, Y4).\nMoreover, desirability values were estimated for selection of the optimized formulation 24<\/sup>.<\/p>\n\n\n\n

Characterization of the prepared fluconazole nanovesicles Analysis of vesicular size, polydispersity index and zeta potential<\/strong><\/p>\n\n\n\n

Dynamic light scattering adopted in the Zetasizer (Nano\nZS, Malvern Instruments, Malvern, UK) were\nutilized for the analysis of the PS, PDI and ZP of the nanovesicular\nformulations. Samples taken from each formulation were diluted until being hazy before\nanalysis.<\/p>\n\n\n\n

Determination of the encapsulation efficiency of the prepared fluconazole nanovesicles<\/strong><\/p>\n\n\n\n

Fluconazole-loaded nanovesicles <\/em>was centrifuged and separated from the un-encapsulated drug at 20,000 rpm for 1 h, at temperature 40\u00b0<\/sup>C using high speed cooling centrifuge (Andreas Hettich<\/p>\n\n\n\n

GmbH and Co. KG, Tuttlingen, Germany). The supernatant was analyzed using UV- spectrophotometer (Shimadzu, Tokyo, Japan)\nto determine the fluconazole concentration based on a pre-established calibration curve.<\/p>\n\n\n\n

In-vitro drug release from the optimized nanovesicular formulation<\/strong><\/p>\n\n\n\n

Drug release from the optimized\nnanovesicular formulations and the drug suspension was determined\nusing the reverse dialysis technique in USP II dissolution apparatus (Pharm\nTest, Hainburg, Germany)25<\/sup>.\nThe used dissolution medium was 900 mL phosphate buffer (pH 6.6). Dialysis bags (molecular weight cut off\n12-14 kDa) was filled by 3 ml of the dissolution medium. The rotation speed adjusted to 50 rpm and the temperature set at\n37 \u00b1 1 o<\/sup>C. Samples were taken at\nthe following time intervals: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 h. The\ndrug concentration analyzed\nspectrophotometrically at the predetermined \u03bbmax.<\/p>\n\n\n\n

PS values for the prepared fluconazole nanovesicles ranged between 450 and 753, as shown in Table 1.<\/p>\n\n\n\n

Microbiological experiment<\/strong><\/p>\n\n\n\n

Different volumes (50 \u00b5L, 100 \u00b5L, 150 \u00b5L) of each one of\nthe 9 different nano forms of Fluconazole were added to 50 \u00b5L of Candida suspension in three different tubes, mixed thoroughly\nand incubated for 2 minutes. 50 \u00b5L is\nthen taken from each mixture and dispensed to the plate of Sabouraud Dextrose agar and is then\nincubated at 37 \u00b0C for 48 hours. Similarly, the procedure is repeated with the normal form of the\nFluconazole for the comparison of Candida\n<\/em>growth, in addition to normal\nsaline as negative control. Colonies then counted using colony counter and the number of CFUs\/mL plotted against\nconcentration for different Nano forms of Fluconazole and difference has been estimated.<\/p>\n\n\n\n

The colonies were enumerated using colony counter machine (Colony counter SC6 PLUS – Stuart) and the number of CFUs\/mL were plotted against concentration for different Nano forms of the Fluconazole and the variation was estimated.<\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

The observed colony count shows a significant difference and increased effectiveness between the different nano forms in comparison to the normal form of Fluconazole as indicated in (figure 1). There is a significant decrease of colonies as the concentration of the nano agent increased (table 1), the results indicate a significant difference among all the nine forms used in three different concentrations 50 \u00b5L,100 \u00b5L and 150 \u00b5L after 48 hours of incubation at 37 \u00b0C. Nano agent 5 and 6 depict no significance in comparison to the normal form of Fluconazole (table 2. and 3). The maximum effect has been observed in the plate with highest volume 150 \u00b5L. The nano forms 1, 2, 3, 4, 7, 8 and 9 shows significant difference in comparison to the difference in concentration used to the normal form of Fluconazole (figure. 2) (table. 4). The colony count difference increases variably with increased concentration as seen in (figure 3).<\/p>\n\n\n\n

Fluconazole (FLZ) is used to treat cutaneous fungal\ninfections for more than 35 years6<\/sup>. FLZ has a moderately large molecular size and is hydrophobic, which\npromotes its absorption via intravenous or\noral routes but makes it difficult to apply topically. In recent years,\nnano-based techniques for eliminating\nFluconazole side effects and increasing medication efficiency have been\ninvestigated. The current\noverview examines nano-drug\ndelivery technologies used to increase\nFluconazole efficacy.\nNanoparticles have received renewed interest in recent decades for the\nmanagement of fungal infections,\nresistance, and mutations [7]<\/sup>. The goal of this study was to create\nfluconazole nanoparticles (NPs) in various\nratios to achieve\nthe lowest particle\nsize possible. The solvent evaporation technique was used to create\nnine formulas. The synthesized formula was then tested on Candida albicans <\/em>positive strains, and the effect of each form was investigated further. According to\nthe findings of the current study, Nano versions of Fluconazole are expected to\nbe effective against pure strains of\nCandida albicans. Similar findings were obtained in study by Pandey and Ahmed 1,<\/sup> 2<\/sup>.<\/p>\n\n\n\n

Finding newer and more potent antifungal medicines to\ncombat the resistant strains is required as drug\nresistance develops. Azoles have a limited bioavailability because they are\npoorly soluble in water. In most cases, the drug is dispersed\nunevenly throughout the body, and certain cells participate\nin the drug’s metabolization in the blood stream. Before use, the medication is\nonly partially eliminated from the\nbody. Antifungal agents have been modified thus far using a few procedures. Modern drug systems are now\nbeing produced and administered by new pharma firms. The most significant of these systems are hydrogels,\nnanofibers, nanoliposomes, niosomes, and nano-dendrimers, all of which\nare currently used frequently 27<\/sup>.<\/p>\n\n\n\n

Particle size and zeta potential range (753.15 \u00b1 6.24 to 450.08 \u00b1 7.66 nm) and (7.25\n\u00b1 0.68 to -0.465<\/p>\n\n\n\n

\u00b1 0.02 mV), respectively. Particle size and distribution width is often one of the most important quality-related parameters which affect other macroscopic properties of the nano-particle. Particles larger than 1 \u00b5m and an increase in their number can show their physical instability 26<\/sup>. Zeta potential is an important factor in determining the stability of the colloidal system and is the best indicator for determining the surface electric status of dispersions. In this study, the particle size of less than 1 \u00b5m and zeta potential of (7.25 \u00b1 0.68 to -0.465 \u00b1 0.02 mV) indicated and confirmed the stability of the formulated nano- Fluconazole.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Difference in colony count between Fluconazole (A) and Nano agents (B).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Effect of Fluconazole and Nano agent 1,2,3,7,8,9 on Candida albicans<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 3: <\/strong>Difference in colony count between the normal form Fluconazole and Nano form 1, 2 and 9.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 1: Experimental runs, independent variables, and Measured responses of the central composite response surface experimental design for Fluconazole nanovesicular formulations.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

 <\/p>\n<\/td>\n

\n

Tween\/Cetyl (T\/C) ratio<\/strong><\/p>\n<\/td>\n

\n

Chitosan %<\/strong><\/p>\n<\/td>\n

\n

PS (nm)<\/strong><\/p>\n<\/td>\n

\n

 <\/strong>PDI<\/strong><\/p>\n<\/td>\n

\n

ZP (mV)<\/strong><\/p>\n<\/td>\n

\n

EE (%)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

F1<\/strong><\/p>\n<\/td>\n

\n

5<\/p>\n<\/td>\n

\n

0.1<\/p>\n<\/td>\n

\n

753.15 \u00b1 6.24<\/p>\n<\/td>\n

\n

1 \u00b1 0.00<\/p>\n<\/td>\n

\n

7.25 \u00b1 0.68<\/p>\n<\/td>\n

\n

96.55 \u00b1 2.64<\/p>\n<\/td>\n<\/tr>\n

\n

F2<\/strong><\/p>\n<\/td>\n

\n

5<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

693.08 \u00b1 3.21<\/p>\n<\/td>\n

\n

0.984 \u00b1 0.04<\/p>\n<\/td>\n

\n

-0.72 \u00b1 0.24<\/p>\n<\/td>\n

\n

94.53 \u00b1 1.58<\/p>\n<\/td>\n<\/tr>\n

\n

F3<\/strong><\/p>\n<\/td>\n

\n

5<\/p>\n<\/td>\n

\n

0.3<\/p>\n<\/td>\n

\n

723.47 \u00b1 1.97<\/p>\n<\/td>\n

\n

0.971 \u00b1 0.05<\/p>\n<\/td>\n

\n

3.63 \u00b1 0.17<\/p>\n<\/td>\n

\n

94.44 \u00b1 3.05<\/p>\n<\/td>\n<\/tr>\n

\n

F4<\/strong><\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.1<\/p>\n<\/td>\n

\n

619.24 \u00b1 9.04<\/p>\n<\/td>\n

\n

0.617 \u00b1 0.03<\/p>\n<\/td>\n

\n

0.17 \u00b1 0.06<\/p>\n<\/td>\n

\n

93.711 \u00b1 1.14<\/p>\n<\/td>\n<\/tr>\n

\n

F5<\/strong><\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

681.65 \u00b1 2.43<\/p>\n<\/td>\n

\n

0.759 \u00b1 0.04<\/p>\n<\/td>\n

\n

-0.304 \u00b1 0.03<\/p>\n<\/td>\n

\n

92.49 \u00b1 2.37<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

684.17 \u00b1 5.64<\/p>\n<\/td>\n

\n

0.638 \u00b1 0.02<\/p>\n<\/td>\n

\n

0.143 \u00b1 0.02<\/p>\n<\/td>\n

\n

92.61 \u00b1 1.45<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

620.62 \u00b1 1.67<\/p>\n<\/td>\n

\n

0.691 \u00b1 0.05<\/p>\n<\/td>\n

\n

0.242 \u00b1 0.06<\/p>\n<\/td>\n

\n

92.00 \u00b1 1.02<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

651.90 \u00b1 3.58<\/p>\n<\/td>\n

\n

0.725 \u00b1 0.03<\/p>\n<\/td>\n

\n

0.531 \u00b1 0.11<\/p>\n<\/td>\n

\n

92.72 \u00b1 0.08<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

641.26 \u00b1 7.69<\/p>\n<\/td>\n

\n

0.677 \u00b1 0.01<\/p>\n<\/td>\n

\n

0.372 \u00b1 0.25<\/p>\n<\/td>\n

\n

92.92 \u00b1 2.03<\/p>\n<\/td>\n<\/tr>\n

\n

F6<\/strong><\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

0.3<\/p>\n<\/td>\n

\n

689.33 \u00b1 8.30<\/p>\n<\/td>\n

\n

0.543 \u00b1 0.03<\/p>\n<\/td>\n

\n

-2.456 \u00b1 0.07<\/p>\n<\/td>\n

\n

92.25 \u00b1 0.06<\/p>\n<\/td>\n<\/tr>\n

\n

F7<\/strong><\/p>\n<\/td>\n

\n

15<\/p>\n<\/td>\n

\n

0.1<\/p>\n<\/td>\n

\n

480.35 \u00b1 4.69<\/p>\n<\/td>\n

\n

0.495 \u00b1 0.02<\/p>\n<\/td>\n

\n

2.256 \u00b1 0.13<\/p>\n<\/td>\n

\n

94.42 \u00b1 2.41<\/p>\n<\/td>\n<\/tr>\n

\n

F8<\/strong><\/p>\n<\/td>\n

\n

15<\/p>\n<\/td>\n

\n

0.2<\/p>\n<\/td>\n

\n

550.15 \u00b1 1.83<\/p>\n<\/td>\n

\n

0.152 \u00b1 0.01<\/p>\n<\/td>\n

\n

-2.21 \u00b1 0.37<\/p>\n<\/td>\n

\n

93.61 \u00b1 0.09<\/p>\n<\/td>\n<\/tr>\n

\n

F9<\/strong><\/p>\n<\/td>\n

\n

15<\/p>\n<\/td>\n

\n

0.3<\/p>\n<\/td>\n

\n

450.08 \u00b1 7.66<\/p>\n<\/td>\n

\n

0.339 \u00b1 0.01<\/p>\n<\/td>\n

\n

-0.465 \u00b1 0.02<\/p>\n<\/td>\n

\n

92.97 \u00b1 1.73<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 2: Comparison of colony count result yield from Normal Fluconazole and nano Fluconazole form (5)<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n
\n

Type of Fluconazole<\/strong><\/p>\n<\/td>\n

\n

50 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

100 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

150 \u00b5L<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Fluconazole (Normal<\/p>\n

Form)<\/p>\n<\/td>\n

\n

352<\/p>\n<\/td>\n

\n

279<\/p>\n<\/td>\n

\n

253<\/p>\n<\/td>\n<\/tr>\n

\n

Fluconazole nano agent<\/p>\n

5<\/p>\n<\/td>\n

\n

427<\/p>\n<\/td>\n

\n

512<\/p>\n<\/td>\n

\n

451<\/p>\n<\/td>\n<\/tr>\n

\n

Difference in %<\/p>\n<\/td>\n

\n

+21.315%<\/p>\n<\/td>\n

\n

+83.51%<\/p>\n<\/td>\n

\n

+78.26%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 3: Comparison of colony count result yield from Normal Fluconazole and nano Fluconazole form (6)<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n
\n

Type of Fluconazole<\/strong><\/p>\n<\/td>\n

\n

50 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

100 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

150 \u00b5L<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Fluconazole (Normal<\/p>\n

Form)<\/p>\n<\/td>\n

\n

352<\/p>\n<\/td>\n

\n

279<\/p>\n<\/td>\n

\n

253<\/p>\n<\/td>\n<\/tr>\n

\n

Fluconazole nano<\/p>\n

agent 6<\/p>\n<\/td>\n

\n

426<\/p>\n<\/td>\n

\n

310<\/p>\n<\/td>\n

\n

300<\/p>\n<\/td>\n<\/tr>\n

\n

Difference in %<\/p>\n<\/td>\n

\n

+21.02<\/p>\n<\/td>\n

\n

+11.11%<\/p>\n<\/td>\n

\n

+47%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 4: Shows the decrease percentage of the colony count of the 9 forms of the nano fluconazole compared to the normal form except in number 5 and 6.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Difference in %<\/strong><\/p>\n<\/td>\n

\n

50 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

100 \u00b5L<\/strong><\/p>\n<\/td>\n

\n

150 \u00b5L<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Nano 1<\/strong><\/p>\n<\/td>\n

\n

82.10%<\/p>\n<\/td>\n

\n

92.11%<\/p>\n<\/td>\n

\n

94.47%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 2<\/strong><\/p>\n<\/td>\n

\n

85.8%<\/p>\n<\/td>\n

\n

94.62%<\/p>\n<\/td>\n

\n

96.05%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 3<\/strong><\/p>\n<\/td>\n

\n

+47.4<\/p>\n<\/td>\n

\n

12.9%<\/p>\n<\/td>\n

\n

62.85%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 4<\/strong><\/p>\n<\/td>\n

\n

29.31%<\/p>\n<\/td>\n

\n

65.59%<\/p>\n<\/td>\n

\n

68.83<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 5<\/strong><\/p>\n<\/td>\n

\n

+21.315%<\/p>\n<\/td>\n

\n

+83.51%<\/p>\n<\/td>\n

\n

+78.26%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 6<\/strong><\/p>\n<\/td>\n

\n

+21.02<\/p>\n<\/td>\n

\n

+11.11%<\/p>\n<\/td>\n

\n

+47%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 7<\/strong><\/p>\n<\/td>\n

\n

62%<\/p>\n<\/td>\n

\n

77.06%<\/p>\n<\/td>\n

\n

80.24%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 8<\/strong><\/p>\n<\/td>\n

\n

51.4%<\/p>\n<\/td>\n

\n

69.18%<\/p>\n<\/td>\n

\n

81.82%<\/p>\n<\/td>\n<\/tr>\n

\n

Nano 9<\/strong><\/p>\n<\/td>\n

\n

76.14%<\/p>\n<\/td>\n

\n

79.12%<\/p>\n<\/td>\n

\n

82.61%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

The following conclusions may be drawn about the effect\nof each nano form of Fluconazole on Candida\nalbicans. The nano forms of Fluconazole are estimated to work effectively\nagainst the pure strains of Candida\nalbicans. With increased concentration of nano agent there is significant decrease in the growth of Candida. The\nsmall size of the nano agents therefore helps in better penetration of Fluconazole and proved to work effectively\nagainst the Candida albicans. The nano agents\nhave shown significant variance in decreasing the colony of candida albicans in\ncomparison to the normal form of Fluconazole.<\/p>\n\n\n\n

In conclusion we found that nano-fluconazole had a\nbetter affect than aqueous fluconazole. In light of these findings,\nthe optimized nano vesicular formula\ncould be considered as very promising\nnanocarriers for the application of fluconazole through\nincreasing its antifungal effect.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

The authors would like to thank all microbiology staff for their\ncollaboration in this study. The authors would also like to thank the college\nof Pharmacy, GMU for his kind support\nwith providing the antifungal.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

All authors confirmed\nthere is no conflict of interest.<\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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