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image of Treating Burn Infections With Topical Delivery of Positively Charged Norfloxacin-Loaded Lipid-Polymer Hybrid Nanoparticles

Abstract

Background

Norfloxacin (NFX) is a wide-spectrum antibacterial agent that suffers from low water solubility and first-pass metabolism. This diminishes its oral bioavailability by 60-70%.

Objective

This work aims to formulate a topical gel of NFX-loaded lipid polymer hybrid nanoparticles (NFX-LPHNPs) that combine the merits of liposomes and polymeric nanoparticles to overcome these problems.

Methods

NFX-LPHNPs formulations were developed using Precirol ATO (lipid) and Eudragit RL100 (polymer). They were characterized for particle size, uniformity of distribution, entrapment efficiency, zeta potential, and in-vitro release. Box–Behnken design was applied to study sequentially different variables' impact on material attributes. Then the optimized formula was re-evaluated, and incorporated in an HPMC-gel formulation. The gel formulation was evaluated for its physical properties, -release, and antibacterial activity.

Results

NFX-LPHNPs exhibited particle sizes ranging from 28.92 to 730.30 nm. Particles were uniformly distributed with a positively charged surface (indicated by zeta potential with values from +3.91 to +60.2 mV). Formulations showed a % cumulative drug release of 87.9-100% in 8 h. The optimized formula showed a satisfied fit of measured-to-predicted responses with 159 nm particle size, 92.61% release and 79.2% entrapment efficiency Gel formulation showed a sustained release over 24 h. Antibacterial testing against and revealed enhanced activity of NFX-LPHNPs against these pathogens compared to bare NFX loaded gel.

Conclusion

These results illustrated the high potential of lipid-polymer hybrid nanoparticles to improve NFX activity against resistant pathogens common in burn infections. Moreover, the topical application helps overcome Norfloxacin oral-associated problems.

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2024-12-09
2025-01-20
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References

  1. Bourgi J. Said J.M. Yaakoub C. Atallah B. Al Akkary N. Sleiman Z. Ghanimé G. Bacterial infection profile and predictors among patients admitted to a burn care center: A retrospective study. Burns 2020 46 8 1968 1976 10.1016/j.burns.2020.05.004 32522390
    [Google Scholar]
  2. Kelly E.J. Oliver M.A. Carney B.C. Shupp J.W. Infection and burn injury. European Burn Journal 2022 3 1 165 179 10.3390/ebj3010014
    [Google Scholar]
  3. Elmassry M.M. Mudaliar N.S. Colmer-Hamood J.A. San Francisco M.J. Griswold J.A. Dissanaike S. Hamood A.N. New markers for sepsis caused by Pseudomonas aeruginosa during burn infection. Metabolomics 2020 16 3 40 10.1007/s11306‑020‑01658‑2 32170472
    [Google Scholar]
  4. Thakur K. Sharma G. Singh B. Chhibber S. Katare O.P. Nano-engineered lipid-polymer hybrid nanoparticles of fusidic acid: An investigative study on dermatokinetics profile and MRSA-infected burn wound model. Drug Deliv. Transl. Res. 2019 9 4 748 763 10.1007/s13346‑019‑00616‑3 30652257
    [Google Scholar]
  5. Lu J. Yang M. Zhan M. Xu X. Yue J. Xu T. Antibiotics for treating infected burn wounds. Cochrane Database Syst. Rev. 2017 2017 7
    [Google Scholar]
  6. Debalkie A. Guadie A. Kassa A. Tefera M. Selective determination of norfloxacin in pharmaceutical formulations and human urine samples using poly(8-aminonaphthaline-2-sulfonic acid)-modified glassy carbon electrodes. ACS Omega 2023 8 29 25758 25765 10.1021/acsomega.3c00805 37521652
    [Google Scholar]
  7. Dua K. Malipeddi V.R. Madan J. Gupta G. Chakravarthi S. Awasthi R. Kikuchi I.S. De Jesus Andreoli Pinto T. Norfloxacin and metronidazole topical formulations for effective treatment of bacterial infections and burn wounds. Interv. Med. Appl. Sci. 2016 8 2 68 76 10.1556/1646.8.2016.2.4 28386462
    [Google Scholar]
  8. Khan M.A. Khan S. Kazi M. Alshehri S.M. Shahid M. Khan S.U. Hussain Z. Sohail M. Shafique M. Hamid H.A. Kamran M. Elhissi A. Wasim M. Thu H.E. Norfloxacin loaded lipid polymer hybrid nanoparticles for oral administration: Fabrication, characterization, in silico modelling and toxicity evaluation. Pharmaceutics 2021 13 10 1632 10.3390/pharmaceutics13101632 34683925
    [Google Scholar]
  9. Goettsch W. van Pelt W. Nagelkerke N. Hendrix M.G. Buiting A.G. Petit P.L. Sabbe L.J. van Griethuysen A.J. de Neeling A.J. Increasing resistance to fluoroquinolones in Escherichia coli from urinary tract infections in The Netherlands. J. Antimicrob. Chemother. 2000 46 2 223 228 10.1093/jac/46.2.223 10933644
    [Google Scholar]
  10. Loganathan V. Manimaran S. Jaswanth A. Sulaiman A. Reddy M. Kumar B.S. Rajaseskaran A. The effects of polymers and permeation enhancers on releases of flubiprofen from gel formulations. Indian J. Pharm. Sci. 2001 63 3 200 204
    [Google Scholar]
  11. Yeh Y.C. Huang T.H. Yang S.C. Chen C.C. Fang J.Y. Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances. Front Chem. 2020 8 286 10.3389/fchem.2020.00286 32391321
    [Google Scholar]
  12. Mba I.E. Nweze E.I. Nanoparticles as therapeutic options for treating multidrug-resistant bacteria: Research progress, challenges, and prospects. World J. Microbiol. Biotechnol. 2021 37 6 108 10.1007/s11274‑021‑03070‑x 34046779
    [Google Scholar]
  13. Mukherjee A. Waters A.K. Kalyan P. Achrol A.S. Kesari S. Yenugonda V.M. Lipid–polymer hybrid nanoparticles as a next-generation drug delivery platform: State of the art, emerging technologies, and perspectives. Int. J. Nanomedicine 2019 14 1937 1952 10.2147/IJN.S198353 30936695
    [Google Scholar]
  14. Gajbhiye K.R. Salve R. Narwade M. Sheikh A. Kesharwani P. Gajbhiye V. Lipid polymer hybrid nanoparticles: A custom-tailored next-generation approach for cancer therapeutics. Mol. Cancer 2023 22 1 160 10.1186/s12943‑023‑01849‑0 37784179
    [Google Scholar]
  15. Elhassan E. Devnarain N. Mohammed M. Govender T. Omolo C.A. Engineering hybrid nanosystems for efficient and targeted delivery against bacterial infections. J. Control. Release 2022 351 598 622 10.1016/j.jconrel.2022.09.052 36183972
    [Google Scholar]
  16. Patole V.C. Awari D. Chaudhari S. Resveratrol-loaded microsponge gel for wound healing: In vitro/and in vivo/ characterization. Turk. J. Pharm. Sci. 2023 20 1 23 34 10.4274/tjps.galenos.2022.93275 36864580
    [Google Scholar]
  17. Dave V. Yadav R.B. Kushwaha K. Yadav S. Sharma S. Agrawal U. Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system. Bioact. Mater. 2017 2 4 269 280 10.1016/j.bioactmat.2017.07.002 29744436
    [Google Scholar]
  18. Jamshidnejad-Tosaramandani T. Kashanian S. Karimi I. Schiöth H.B. Synthesis of an insulin-loaded mucoadhesive nanoparticle designed for intranasal administration: Focus on new diffusion media. Front. Pharmacol. 2023 14 1227423 10.3389/fphar.2023.1227423 37701036
    [Google Scholar]
  19. Hoseini B. Jaafari M.R. Golabpour A. Momtazi-Borojeni A.A. Eslami S. Optimizing nanoliposomal formulations: Assessing factors affecting entrapment efficiency of curcumin-loaded liposomes using machine learning. Int. J. Pharm. 2023 646 123414 10.1016/j.ijpharm.2023.123414 37714314
    [Google Scholar]
  20. Jyothi D. Koland M. Formulation and evaluation of an herbal anti-inflammatory gel containing Trigonella foenum greacum seed extract. Int. J. Pharm. Pharm. Sci. 2016 8 1 41 44
    [Google Scholar]
  21. Yahoum M.M. Toumi S. Tahraoui H. Lefnaoui S. Kebir M. Amrane A. Assadi A.A. Zhang J. Mouni L. Formulation and evaluation of xanthan gum microspheres for the sustained release of metformin hydrochloride. Micromachines 2023 14 3 609 10.3390/mi14030609 36985017
    [Google Scholar]
  22. Jamous Y.F. Altwaijry N.A. Saleem M.T.S. Alrayes A.F. Albishi S.M. Almeshari M.A. Formulation and characterization of solid lipid nanoparticles loaded with troxerutin. Processes (Basel) 2023 11 10 3039 10.3390/pr11103039
    [Google Scholar]
  23. Al-Saidan S.M. Krishnaiah Y.S.R. Chandrasekhar D.V. Lalla J.K. Rama B. Jayaram B. Bhaskar P. Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil. Skin Pharmacol. Physiol. 2004 17 6 310 320 10.1159/000081117 15528962
    [Google Scholar]
  24. Elfakhri K.H. Niu M. Ghosh P. Ramezanli T. Raney S.G. Kamal N. Ashraf M. Zidan A.S. Understanding the impact of formulation design on microstructure and drug release from porous microparticle-based tretinoin topical gels. Int. J. Pharm. 2024 653 123794 10.1016/j.ijpharm.2024.123794 38216074
    [Google Scholar]
  25. Hirun N. Kraisit P. Drug-polymers composite matrix tablets: Effect of hydroxypropyl methylcellulose (HPMC) K-series on porosity, compatibility, and release behavior of the tablet containing a BCS class I drug. Polymers (Basel) 2022 14 16 3406 10.3390/polym14163406 36015661
    [Google Scholar]
  26. Budhori A. Tiwari A. Tiwari V. Sharma A. Kumar M. Gautam G. Virmani T. Kumar G. Alhalmi A. Noman O.M. Hasson S. Mothana R.A. QbD design, formulation, optimization and evaluation of trans-tympanic reverse gelatination gel of norfloxacin: Investigating gene-gene interactions to enhance therapeutic efficacy. Gels 2023 9 8 657 10.3390/gels9080657 37623112
    [Google Scholar]
  27. Nascimento G.G.F. Locatelli J. Freitas P.C. Silva G.L. Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria. Braz. J. Microbiol. 2000 31 4 247 256 10.1590/S1517‑83822000000400003
    [Google Scholar]
  28. Gonzalez-Pastor R. Carrera-Pacheco S.E. Zúñiga-Miranda J. Rodríguez-Pólit C. Mayorga-Ramos A. Guamán L.P. Barba-Ostria C. Current landscape of methods to evaluate antimicrobial activity of natural extracts. Molecules 2023 28 3 1068 10.3390/molecules28031068 36770734
    [Google Scholar]
  29. Gajra B. Dalwadi C. Patel R. Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using box behnken design. Daru 2015 23 1 3 10.1186/s40199‑014‑0087‑0 25604353
    [Google Scholar]
  30. Cetin M. Atila A. Kadioglu Y. Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. AAPS PharmSciTech 2010 11 3 1250 1256 10.1208/s12249‑010‑9489‑6 20697984
    [Google Scholar]
  31. Darwish M.K.M. El-Enin A.S.M.A. Mohammed K.H.A. Optimized nanoparticles for enhanced oral bioavailability of a poorly soluble drug: Solid lipid nanoparticles versus nanostructured lipid carriers. Pharm. Nanotechnol. 2022 10 1 69 87 10.2174/2211738510666220210110003 35142275
    [Google Scholar]
  32. Valizadeh H. Jelvehgari M. Nokhodchi A. Rezapour M. Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method. Indian J. Pharm. Sci. 2010 72 1 72 78 10.4103/0250‑474X.62251 20582193
    [Google Scholar]
  33. Salatin S. Barar J. Barzegar-Jalali M. Adibkia K. Alami-Milani M. Jelvehgari M. Formulation and evaluation of eudragit RL-100 nanoparticles loaded in-situ forming gel for intranasal delivery of rivastigmine. Adv. Pharm. Bull. 2019 10 1 20 29 10.15171/apb.2020.003 32002358
    [Google Scholar]
  34. Hashem H.E. Amr A.E.G.E. Almehizia A.A. Naglah A.M. Kariuki B.M. Eassa H.A. Nossier E.S. Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: Design, structure determination, anticancer evaluation and in silico studies. Molecules 2023 28 21 7252 10.3390/molecules28217252 37959672
    [Google Scholar]
  35. Das S. Suresh P.K. Desmukh R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine 2010 6 2 318 323 10.1016/j.nano.2009.09.002 19800990
    [Google Scholar]
  36. Awadeen R.H. Boughdady M.F. Zaghloul R.A. Elsaed W.M. Abu Hashim I.I. Meshali M.M. Formulation of lipid polymer hybrid nanoparticles of the phytochemical Fisetin and its in vivo assessment against severe acute pancreatitis. Sci. Rep. 2023 13 1 19110 10.1038/s41598‑023‑46215‑8 37925581
    [Google Scholar]
  37. Honary S. Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 1). Trop. J. Pharm. Res. 2013 12 2 255 264
    [Google Scholar]
  38. Ali H.S.M. York P. Ali A.M.A. Blagden N. Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling. J. Control. Release 2011 149 2 175 181 10.1016/j.jconrel.2010.10.007 20946923
    [Google Scholar]
  39. Ram A. Raj M. P.; Kumar, N.; Raj, R. Comparative Study of Eudragit RS 100 and RL 100 Nanoparticles as Ophthalmic Vehicle for Fungal Infection. Pharm. Nanotechnol. 2016 4 4 316 328 10.2174/2211738504666160906144633
    [Google Scholar]
  40. Syed A. Devi V.K. Potential of targeted drug delivery systems in treatment of rheumatoid arthritis. J. Drug Deliv. Sci. Technol. 2019 53 101217 10.1016/j.jddst.2019.101217
    [Google Scholar]
  41. Supraba W. Juliantoni Y. Ananto A.D. The effect of stirring speeds to the entrapment efficiency in a nanoparticles formulation of Java Plum’s seed ethanol extract (Syzygium cumini). Acta Chimica Asiana 2021 4 1 197 103 10.29303/aca.v4i1.50
    [Google Scholar]
  42. Javed S. Ropel D. Vogt D. Sodium ethoxide as an environmentally benign and cost-effective catalyst for chemical depolymerization of post-consumer PET waste. Green Chem. 2023 25 4 1442 1452 10.1039/D2GC04548F
    [Google Scholar]
  43. Singh G. Ahuja N. Sharma P. Capalash N. Response surface methodology for the optimized production of an alkalophilic lassase from gamma-proteobacterium JB. BioResources 2009 4 2 544 553 10.15376/biores.4.2.544‑553
    [Google Scholar]
  44. Gunda R.K. Manchineni P.R. Statistical design and optimization of sustained release formulations of pravastatin. Turk. J. Pharm. Sci. 2020 17 2 221 227 10.4274/tjps.galenos.2019.70048 32454783
    [Google Scholar]
  45. Sebastian G. Computational tools assisted formulation optimization of nebivolol hydrochloride loaded PLGA nanoparticles by 32 factorial designs. Int J App Pharm 2022 14 4 251 258
    [Google Scholar]
  46. Yang X. Patel S. Sheng Y. Pal D. Mitra A.K. Statistical design for formulation optimization of hydrocortisone butyrate-loaded PLGA nanoparticles. AAPS PharmSciTech 2014 15 3 569 587 10.1208/s12249‑014‑0072‑4 24504495
    [Google Scholar]
  47. Rahmanian-Devin P. Askari V.R. Sanei-Far Z. Baradaran Rahimi V. Kamali H. Jaafari M.R. Golmohammadzadeh S. Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions. Biomed. Pharmacother. 2023 168 115823 10.1016/j.biopha.2023.115823 37924792
    [Google Scholar]
  48. Huguet-Casquero A. Moreno-Sastre M. López-Méndez T.B. Gainza E. Pedraz J.L. Encapsulation of oleuropein in nanostructured lipid carriers: Biocompatibility and antioxidant efficacy in lung epithelial cells. Pharmaceutics 2020 12 5 429 10.3390/pharmaceutics12050429 32384817
    [Google Scholar]
  49. Sahoo S. Chakraborti C.K. Behera P.K. Mishra S.C. FTIR and Raman Spectroscopic Investigations of a Norfloxacin/Carbopol934 Polymerie Suspension. J. Young Pharm. 2012 4 3 138 145 10.4103/0975‑1483.100017 23112532
    [Google Scholar]
  50. Ali A. Madni A. Shah H. Jamshaid T. Jan N. Khan S. Khan M.M. Mahmood M.A. Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma. PLoS One 2023 18 2 e0281004 10.1371/journal.pone.0281004 36854019
    [Google Scholar]
  51. Zhang L. Chan J.M. Gu F.X. Rhee J.W. Wang A.Z. Radovic-Moreno A.F. Alexis F. Langer R. Farokhzad O.C. Self-assembled lipid-polymer hybrid nanoparticles: A robust drug delivery platform. ACS Nano 2008 2 8 1696 1702 10.1021/nn800275r 19206374
    [Google Scholar]
  52. Miastkowska M. Kulawik-Pióro A. Szczurek M. Nanoemulsion gel formulation optimization for burn wounds: Analysis of rheological and sensory properties. Processes (Basel) 2020 8 11 1416 10.3390/pr8111416
    [Google Scholar]
  53. Safitri F.I. Nawangsari D. Febrina D. Overview: Application of Carbopol 940 in Gel. Atlantis Press 2021 80 84
    [Google Scholar]
  54. Ismail N. Mat Amin K. Razali M. Antibacterial study of gellan gum (GG) film incorporated norfloxacin. J. Pure Appl. Microbiol. 2019 13 2 1095 1102 10.22207/JPAM.13.2.48
    [Google Scholar]
  55. Jaglal Y. Osman N. Omolo C.A. Mocktar C. Devnarain N. Govender T. Formulation of pH-responsive lipid-polymer hybrid nanoparticles for co-delivery and enhancement of the antibacterial activity of vancomycin and 18β-glycyrrhetinic acid. J. Drug Deliv. Sci. Technol. 2021 64 102607 10.1016/j.jddst.2021.102607
    [Google Scholar]
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