ABSTRACT
Purpose
Nystatin loaded PLGA and PLGA-Glucosamine nanoparticles were formulated. PLGA were functionalized with Glucosamine (PLGA-GlcN) to enhance the adhesion of nanoparticles to Candida Albicans (C.albicans) cell walls.
Method
Quasi-emulsion solvent diffusion method was employed using PLGA and PLGA-GlcN with various drug–polymer ratios for the preparation of nanoparticles. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency and release properties. DSC, SEM, XRPD, 1H-NMR, and FT-IR were performed to analyze the physicochemical properties of the nanoparticles. Antifungal activity of the nanoparticles was evaluated by determination of MICs against C.albicans.
Results
The spectra of 1H-NMR and FT-IR analysis ensured GlcN functionalization on PLGA nanoparticles. SEM characterization confirmed that particles were in the nanosize range and the particle size for PLGA and PLGA-GlcN nanoparticles were in the range of 108.63 ± 4.5 to 168.8 ± 5.65 nm and 208.76 ± 16.85 nm, respectively. DSC and XRPD analysis ensured reduction of the drug crystallinity in the nanoparticles. PLGA-GlcN nanoparticles exhibit higher antifungal activity than PLGA nanoparticles.
Conclusion
PLGA-GlcN nanoparticles showed more antifungal activity with appropriate physicochemical properties than pure Nystatin and PLGA nanoparticles.
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Abbreviations
- C. albicans:
-
Candida Albicans
- D2O:
-
Deuterium oxide
- DCM:
-
Dichloromethane
- DMAP:
-
4-Dimethylaminopyridine
- DMSO:
-
Dimethylsulfoxide
- DSC:
-
Differential scanning calorimetric
- FT-IR:
-
Fourier transform infrared spectroscopy
- GlcN:
-
Glucosamine
- H-NMR:
-
Proton nuclear magnetic resonance
- HPLC:
-
High performance liquid chromatography
- KBr:
-
Potassium Bromide
- MIC:
-
Minimum inhibitory concentration
- PE:
-
Prediction error
- PEG:
-
Polyethylene glycol
- PLGA:
-
Poly lactic-co-glycolic acid
- PLGA-GlcN:
-
PLGA functionalized with Glucosamine
- PVA:
-
Polyvinyl alcohol
- RSQ:
-
Squared correlation coefficient
- SEM:
-
Scanning Electron Microscope
- XRPD:
-
Powder X-Ray Diffractometry
REFERENCES
Rosato A, Vitali C, Piarulli M, Mazzotta M, Argentieri MP, Mallamaci R. In vitro synergic efficacy of the combination of Nystatin with the essential oils of Origanum vulgare and Pelargonium graveolens against some Candida species. Phytomedicine. 2009;16(10):972–5.
Barkvoll P, Attramadal A. Effect of nystatin and chlorhexidine digluconate on Candida albicans. Oral Surg Oral Med Oral Pathol. 1989;67(3):279–81.
Newman SL, Holly A. Candida albicans is phagocytosed, killed, and processed for antigen presentation by human dendritic cells. Infect Immun. 2001;69(11):6813–22.
Pfaller M, Diekema D, Mendez M, Kibbler C, Erzsebet P, Chang S-C, et al. Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J Clin Microbiol. 2006;44(10):3551–6.
Gillum AM, Tsay EY, Kirsch DR. Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet MGG. 1984;198(1):179–82.
Singh M, Kumar M, Kalaivani R, Manikandan S, Kumaraguru A. Metallic silver nanoparticle: a therapeutic agent in combination with antifungal drug against human fungal pathogen. Bioprocess Biosyst Eng. 2013;36(4):407–15.
He L, Liu Y, Mustapha A, Lin M. Antifungal activity of zinc oxide nanoparticles against Botrytis cinerea and Penicillium expansum. Microbiol Res. 2011;166(3):207–15.
Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B: Biointerfaces. 2010;75(1):1–18.
Niemirowicz K, Durnaś B, Tokajuk G, Głuszek K, Wilczewska AZ, Misztalewska I, et al. Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics. Nanomed: Nanotechnol, Biol Med. 2016;12(8):2395–404.
Hussein-Al-Ali SH, El Zowalaty ME, Kura AU, Geilich B, Fakurazi S, Webster TJ, Hussein MZ. Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite. Biomed Res Int. 2014;2014.
Khalil RM, El Rahman AAA, Kassem MA, El Ridi MS, Samra MMA, Awad GE, et al. Preparation and in vivo assessment of nystatin-loaded solid lipid nanoparticles for topical delivery against cutaneous candidiasis. Int J Med Health Pharm Biomed Eng. 2014;8:401–9.
Khalil R, Kassem M, Elbary AA, El Ridi M, AbouSamra M. Preparation and characterization of nystatin-loaded solid lipid nanoparticles for topical delivery. Int J Pharm Sci Res. 2013;4(6):2292.
Khalil RM, Abd-Elbary A, Kassem MA, El Ridy MS, Samra MMA, Awad GE, et al. Formulation and characterization of nystatin-loaded nanostructured lipid carriers for topical delivery against cutaneous Candidiasis. Br J Pharm Res. 2014;4(4):490.
Melkoumov A, Goupil M, Louhichi F, Raymond M, de Repentigny L, Leclair G. Nystatin nanosizing enhances in vitro and in vivo antifungal activity against Candida albicans. J Antimicrob Chemother. 2013;dkt137.
Monteiro DR, Silva S, Negri M, Gorup LF, Camargo ER, Oliveira R, et al. Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms. Mycoses. 2013;56(6):672–80.
Shahrestani FF, Karazmodeh Z, Dolatabadi NM, Habibpour M, Talebi B, Aghajani J, et al. Nystatin Candida Albicans drug loading by electrospinning: preparation and characterization. Int J Adv Biol Biomed Res. 2016;4(2):220–7.
Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed Nanotechnol Biol Med. 2006;2(1):8–21.
Cui F, Shi K, Zhang L, Tao A, Kawashima Y. Biodegradable nanoparticles loaded with insulin–phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release. 2006;114(2):242–50.
Sahoo SK, Panyam J, Prabha S, Labhasetwar V. Residual polyvinyl alcohol associated with poly (D, L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release. 2002;82(1):105–14.
Gómez-Gaete C, Tsapis N, Besnard M, Bochot A, Fattal E. Encapsulation of dexamethasone into biodegradable polymeric nanoparticles. Int J Pharm. 2007;331(2):153–9.
Lee MA. Nanoparticle-ligand conjugations for targeted drug delivery: processing and applications. 2013.
Wang AZ, Gu F, Zhang L, Chan JM, Radovic-Moreno A, Shaikh MR, Farokhzad OC. Biofunctionalized targeted nanoparticles for therapeutic applications. 2008.
Kumar Khanna V. Targeted delivery of nanomedicines. ISRN pharmacology. 2012;2012.
Saul JM, Annapragada AV, Bellamkonda RV. A dual-ligand approach for enhancing targeting selectivity of therapeutic nanocarriers. J Control Release. 2006;114(3):277–87.
Veerapandian M, Lim SK, Nam HM, Kuppannan G, Yun KS. Glucosamine-functionalized silver glyconanoparticles: characterization and antibacterial activity. Anal Bioanal Chem. 2010;398(2):867–76.
Veerapandian M, Sadhasivam S, Choi J, Yun K. Glucosamine functionalized copper nanoparticles: preparation, characterization and enhancement of anti-bacterial activity by ultraviolet irradiation. Chem Eng J. 2012;209:558–67.
Govindaraju S, Ramasamy M, Baskaran R, Ahn SJ, Yun K. Ultraviolet light and laser irradiation enhances the antibacterial activity of glucosamine-functionalized gold nanoparticles. Int J Nanomedicine. 2015;10:67.
Brown AN, Smith K, Samuels TA, Lu J, Obare SO, Scott ME. Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureus. Appl Environ Microbiol. 2012;78(8):2768–74.
Marimuthu M, Bennet D, Kim S. Self-assembled nanoparticles of PLGA-conjugated glucosamine as a sustained transdermal drug delivery vehicle. Polym J. 2013;45(2):202–9.
Hou S, McCauley LK, Ma PX. Synthesis and erosion properties of PEG‐containing polyanhydrides. Macromol Biosci. 2007;7(5):620–8.
Wu H, Zhu H, Zhuang J, Yang S, Liu C, Cao YC. Water‐soluble nanocrystals through dual‐interaction ligands. Angew Chem Int Ed. 2008;47(20):3730–4.
Mohammadi G, Valizadeh H, Barzegar-Jalali M, Lotfipour F, Adibkia K, Milani M, et al. Development of azithromycin–PLGA nanoparticles: physicochemical characterization and antibacterial effect against Salmonella typhi. Colloids Surf B: Biointerfaces. 2010;80(1):34–9.
Al-Qadi S, Grenha A, Carrión-Recio D, Seijo B, Remuñán-López C. Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations. J Control Release. 2012;157(3):383–90.
Liu L, Guo K, Lu J, Venkatraman SS, Luo D, Ng KC, et al. Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG–TAT for drug delivery across the blood–brain barrier. Biomaterials. 2008;29(10):1509–17.
Veronese FM, Mero A. The impact of PEGylation on biological therapies. BioDrugs. 2008;22(5):315–29.
Basu A, Yang K, Wang M, Liu S, Chintala R, Palm T, et al. Structure-function engineering of interferon-β-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation. Bioconjug Chem. 2006;17(3):618–30.
Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov. 2003;2(3):214–21.
RamaRao B, RamanaRao G, Avadhanulu A. Polymorphism in drugs and its significance in therapeutics. J Sci Ind Res. 1987;46.
Pirooznia N, Hasannia S, Lotfi AS, Ghanei M. Encapsulation of alpha-1 antitrypsin in PLGA nanoparticles: in vitro characterization as an effective aerosol formulation in pulmonary diseases. J Nanobiotechnol. 2012;10(1):20–35.
Mudgil M, Pawar PK. Preparation and in vitro/ex vivo evaluation of moxifloxacin-loaded PLGA nanosuspensions for ophthalmic application. Sci Pharm. 2013;81(2):591.
Javadzadeh Y, Ahadi F, Davaran S, Mohammadi G, Sabzevari A, Adibkia K. Preparation and physicochemical characterization of naproxen–PLGA nanoparticles. Colloids Surf B: Biointerfaces. 2010;81(2):498–502.
Li Y-P, Pei Y-Y, Zhang X-Y, Gu Z-H, Zhou Z-H, Yuan W-F, et al. PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J Control Release. 2001;71(2):203–11.
Salah SM. Formulation of ciprofloxacin hydrochloride loaded biodegradable nanoparticles: Optimization of the formulation variables. J Pharm Res Opin;3(11).
Anitha A, Deepagan V, Rani VD, Menon D, Nair S, Jayakumar R. Preparation, characterization, in vitro drug release and biological studies of curcumin loaded dextran sulphate–chitosan nanoparticles. Carbohydr Polym. 2011;84(3):1158–64.
Jafari-Aghdam N, Adibkia K, Payab S, Barzegar-Jalali M, Parvizpur A, Mohammadi G, Sabzevari A. Methylprednisolone acetate-Eudragit® RS100 electrospuns: preparation and physicochemical characterization. Artif Cells Nanomed Biotechnol. 2014:1–7.
Cunha-Azevedo EP, Silva JR, Martins OP, Siqueira-Moura MP, Bocca AL, Felipe MSS, et al. In vitro antifungal activity and toxicity of itraconazole in DMSA-PLGA nanoparticles. J Nanosci Nanotechnol. 2011;11(3):2308–14.
Tang X, Jiao R, Xie C, Xu L, Huo Z, Dai J, et al. Improved antifungal activity of amphotericin B-loaded TPGS-b-(PCL-ran-PGA) nanoparticles. Int J Clin Exp Med. 2015;8(4):5150.
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Mohammadi, G., Shakeri, A., Fattahi, A. et al. Preparation, Physicochemical Characterization and Anti-fungal Evaluation of Nystatin-Loaded PLGA-Glucosamine Nanoparticles. Pharm Res 34, 301–309 (2017). https://doi.org/10.1007/s11095-016-2062-6
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DOI: https://doi.org/10.1007/s11095-016-2062-6