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Meropenem-Loaded Nanostructured Lipid Carriers For Skin and Soft Tissue Infection Caused by Staphylococcus aureus: Formulation, Design, and Evaluation

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Abstract

Aim

Meropenem hydrochloride (MpM)-loaded nanostructured lipid carriers were designed for the effective management of skin infection caused by Staphylococcus aureus via topical route. The solvent evaporation tactic was preferred to develop nanostructured lipid carriers (NLCs). Stearic acid was used as a solid fatty acid; oleic acid was used as liquid fatty acid and Tween 80 as a surfactant. The Staphylococcus aureus burden was analyzed by pharmacodynamic studies. The skin retention was analyzed by fluorescence microscopy. Spherical shape of NLCs was confirmed by TEM. The optimum particle size of the MpM-NLCs was ~ 126.5 ± 0.9 nm with 79.1 ± 2.3% entrapment (EE) and 0.967 mV zeta potential. The in vitro release studies revealed 81.5 ± 3.1% release of drug in 48 h, while the pure drug was almost completely released (98.4 ± 1.4%) within 24 h confirming the potential of NLCs for sustained topical drug delivery. Skin permeation study also revealed better permeation of drug from NLCs than of plain drug. The prepared MpM-NLCs when stored at 4 ± 2°C for 90 days were found to be more stable when the formulation was stored at 28 ± 2°C. The S. aureus burden was analyzed by evaluating the zone of inhibition (ZOI). The ZOI of MpM alone and MpM-NLC gel was measured and compared with that of the control group. The MpM was found significantly effective when its gel was prepared with NLCs because of its enhanced adhesion property occlusion and ability to sustain release. In overall, the study’s outcomes validated the relevance of NLC’s composition as a vehicle for topical MpM administration in skin diseases caused by Staphylococcus aureus.

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Abbreviations

BBD:

Box-Behnken design

CLSM:

Confocal laser scanning microscopic

DOE:

Design of experiment

EE:

Entrapment efficiency

FITC:

Fluorescein isothiocyanate

MpM:

Meropenem

NLCs:

Nanostructured lipid carriers

SSTI:

Skin and soft tissue infections

TEM:

Transmission electron microscope

USFDA:

US Food and Drug Administration

WHO:

World Health Organization

ZOI:

Zone of inhibition

References

  1. Dryden MS. Skin and soft tissue infection: microbiology and epidemiology. Int J Antimicrob Agents. 2009;34(SUPPL. 1):S2–7. https://doi.org/10.1016/S0924-8579(09)70541-2.

    Article  CAS  PubMed  Google Scholar 

  2. Kaye KS, Petty LA, Shorr AF, Zilberberg MD. Current epidemiology, etiology, and burden of acute skin infections in the United States. Clin Infect Dis. 2019;68(Suppl 3):S193–S9. https://doi.org/10.1093/cid/ciz002.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Barbier F, Timsit JF. Risk stratification for multidrug-resistant bacteria in patients with skin and soft tissue infection. Curr Opin Infect Dis. 2020;33(2):137–45. https://doi.org/10.1097/QCO.0000000000000642.

    PubMed  Google Scholar 

  4. Chifiriuc MC, Holban AM, Curutiu C, Ditu L-M, Mihaescu G, Oprea AE, et al. Antibiotic drug delivery systems for the intracellular targeting of bacterial pathogens. Smart Drug Delivery System. IntechOpen; 2016.

  5. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021;20(2):101–24.

    Article  CAS  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. Prajapati SK, Jain A, Shrivastava C, Jain AK. Hyaluronic acid conjugated multi-walled carbon nanotubes for colon cancer targeting. Int J Biol Macromol. 2019;123:691–703.

    Article  CAS  Google Scholar 

  8. Prajapati SK, Mishra G, Malaiya A, Kesharwani P, Mody N, Jain A. Application of coatings with smart functions. Mini-Reviews in Organic Chemistry. 2021;18(7):943–60.

    Article  CAS  Google Scholar 

  9. Shrestha H, Bala R, Arora S. Lipid-based drug delivery systems. J Pharm 2014;2014.

  10. Chauhan I, Yasir M, Verma M, Singh AP. Nanostructured lipid carriers: a groundbreaking approach for transdermal drug delivery. Advanced Pharmaceutcial Bulletin. 2020;10(2):150–65. https://doi.org/10.34172/apb.2020.021.

    Article  CAS  Google Scholar 

  11. Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018;13(4):288.

    Article  Google Scholar 

  12. Fernandes AV, Pydi CR, Verma R, Jose J, Kumar L. Design, preparation and in vitro characterizations of fluconazole loaded nanostructured lipid carriers. Braz. J Pharm Sci. 2020;56:18069. https://doi.org/10.1590/s2175-97902019000318069.

    CAS  Google Scholar 

  13. Sanad RA, Abdelmalak NS, Elbayoomy TS, Badawi AA. Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs). AAPS PharmSciTech. 2010;11(4):1684–94. https://doi.org/10.1208/s12249-010-9553-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nobari Azar FA, Pezeshki A, Ghanbarzadeh B, Hamishehkar H, Mohammadi M. Nanostructured lipid carriers: promising delivery systems for encapsulation of food ingredients. J Agric Food Res. 2020;2:100084. https://doi.org/10.1016/j.jafr.2020.100084.

    Article  Google Scholar 

  15. Babazadeh A, Ghanbarzadeh B, Hamishehkar H. Novel nanostructured lipid carriers as a promising food grade delivery system for rutin. J Funct Foods. 2016;26:167–75. https://doi.org/10.1016/j.jff.2016.07.017.

    Article  CAS  Google Scholar 

  16. Fish DN. Meropenem in the treatment of complicated skin and soft tissue infections. Ther Clin Risk Manag. 2006;2(4):401–15. https://doi.org/10.2147/tcrm.2006.2.4.401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mohr JF III. Update on the efficacy and tolerability of meropenem in the treatment of serious bacterial infections. Clin Infect Dis. 2008;47(Supplement_1):S41–51.

    Article  CAS  Google Scholar 

  18. Mhango EKG, Kalhapure RS, Jadhav M, Sonawane SJ, Mocktar C, Vepuri S, et al. Preparation and optimization of meropenem-loaded solid lipid nanoparticles: in vitro evaluation and molecular modeling. AAPS PharmSciTech. 2017;18(6):2011–25. https://doi.org/10.1208/s12249-016-0675-z.

    Article  CAS  PubMed  Google Scholar 

  19. Nava-Arzaluz MG, Piñón-Segundo E, Ganem-Rondero A. Lipid nanocarriers as skin drug delivery systems. In: Grumezescu AM, editor. Nanoparticles in pharmacotherapy. Elsevier; 2019. p. 311-90.

  20. Patel D, Patel B, Thakkar H. Lipid based nanocarriers: promising drug delivery system for topical application. Eur J Lipid Sci Technol. 2021;123:2000264. https://doi.org/10.1002/ejlt.202000264.

    Article  CAS  Google Scholar 

  21. Prajapati SK, Mishra G, Malaiya A, Jain A, Mody N, Raichur AM. Antimicrobial application potential of phytoconstituents from turmeric and garlic. In: Pal D, Nayak AK, editors. Bioactive natural products for pharmaceutical applications: Springer Science and Business Media Deutschland GmbH; 2021. p. 409–35.

    Chapter  Google Scholar 

  22. Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B: Biointerfaces. 2005;45(3-4):167–73. https://doi.org/10.1016/j.colsurfb.2005.08.005.

    Article  CAS  PubMed  Google Scholar 

  23. Jain A, Mehra NK, Nahar M, Jain NK. Topical delivery of enoxaparin using nanostructured lipid carrier. J Microencapsul. 2013;30(7):709–15. https://doi.org/10.3109/02652048.2013.778908.

    Article  CAS  PubMed  Google Scholar 

  24. Al-Qushawi A, Rassouli A, Atyabi F, Peighambari SM, Esfandyari-Manesh M, Shams GR, et al. Preparation and characterization of three tilmicosin-loaded lipid nanoparticles: physicochemical properties and in-vitro antibacterial activities. Iran J Pharm Res. 2016;15(4):663–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Prajapati SK, Kesharwani P, Mody N, Jain A, Sharma S. Formulation by design (FbD): an emerging approach to design vesicular nanocarriers. In: Mehra NK, Gulbake A, editors. Micro- and nanotechnologies-based product development. 1st ed.: CRC Press; 2021. p. 15-31.

  26. Moghddam SMM, Ahad A, Aqil M, Imam SS, Sultana Y. Optimization of nanostructured lipid carriers for topical delivery of nimesulide using Box–Behnken design approach. Artif Cells Nanomed Biotechnol. 2017;45(3):617–24. https://doi.org/10.3109/21691401.2016.1167699.

    Article  CAS  PubMed  Google Scholar 

  27. Pradhan M, Yadav K, Singh D, Singh MR. Topical delivery of fluocinolone acetonide integrated NLCs and salicylic acid enriched gel: a potential and synergistic approach in the management of psoriasis. J Drug Deliv Sci Technol. 2021;61:102282. https://doi.org/10.1016/j.jddst.2020.102282.

    Article  CAS  Google Scholar 

  28. Prajapati V, Jain A, Jain R, Sahu S, Kohli DV. Treatment of cutaneous candidiasis through fluconazole encapsulated cubosomes. Drug Deliv Transl Res. 2014;4(5-6):400–8. https://doi.org/10.1007/s13346-014-0202-2.

    Article  CAS  PubMed  Google Scholar 

  29. Jain A, Jain S, Jain R, Kohli DV. Coated chitosan nanoparticles encapsulating caspase 3 activator for effective treatment of colorectral cancer. Drug Deliv Transl Res. 2015;5(6):596–610. https://doi.org/10.1007/s13346-015-0255-x.

    Article  CAS  PubMed  Google Scholar 

  30. Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Phar Cairo Univ. 2015;53(2):147–59. https://doi.org/10.1016/j.bfopcu.2015.10.001.

    Article  Google Scholar 

  31. Phatak AA, Chaudhari PD. Development and evaluation of nanostructured lipid carrier (NLC) based topical delivery of an anti-inflammatory drug. J Pharm Res. 2013;7(8):677–85.

    CAS  Google Scholar 

  32. Cirri M, Bragagni M, Mennini N, Mura P. Development of a new delivery system consisting in “drug–in cyclodextrin–in nanostructured lipid carriers” for ketoprofen topical delivery. Eur J Pharm Biopharm. 2012;80(1):46–53.

    Article  CAS  Google Scholar 

  33. Khan S, Jain P, Sourabh J, Richa J, Jain A. Topical delivery of erythromycin through cubosomes for acne. Pharm Nanotechnol. 2018;06(1). https://doi.org/10.2174/2211738506666180209100222

  34. Draize JH, Woodard G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1994;82(3):377–90.

    Google Scholar 

  35. Jain S, Prajapati SK, Jain S, Jain S, Jain A. Propylene glycol-liposome for anticoagulant drug delivery through skin. J Bionanosci. 2018;12(5):721–7.

    Article  CAS  Google Scholar 

  36. Khan UA, Rahman H, Niaz Z, Qasim M, Khan J, Tayyaba, et al. Antibacterial activity of some medicinal plants against selected human pathogenic bacteria. Eur J Microbiol Immunol. 2013;3(4):272–4. https://doi.org/10.1556/eujmi.3.2013.4.6.

    Article  Google Scholar 

  37. Thirumurugan G, Seshagiri Rao JVLN, Dhanaraju MD. Elucidating pharmacodynamic interaction of silver nanoparticle - topical deliverable antibiotics. Sci Rep. 2016;6(1):1–11. https://doi.org/10.1038/srep29982.

    Article  CAS  Google Scholar 

  38. Liu J, Gong T, Wang C, Zhong Z, Zhang Z. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization. Int J Pharm. 2007;340(1-2):153–62. https://doi.org/10.1016/j.ijpharm.2007.03.009.

    Article  CAS  PubMed  Google Scholar 

  39. Zhao S, Minh LV, Li N, Garamus VM, Handge UA, Liu J, et al. Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release. Colloids Surf B: Biointerfaces. 2016;145:95–103. https://doi.org/10.1016/j.colsurfb.2016.04.027.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

All the authors are thankful to Bhagyoday Tirth Pharmacy College, Sagar, Madhya Pradesh, for providing laboratory facilities, and Dr. H.S. Gour Central University, Sagar, Madhya Pradesh, for TEM facility.

Funding

This study was supported by a Junior Research fellowship from the AICTE, New Delhi.

Author information

Authors and Affiliations

  1. Bhagyoday Tirth Pharmacy College, Sagar, M.P., 470002, India

    Kshipra Rajpoot, Akanksha Malaiya & Aakanchha Jain

  2. Institute of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, 201310, India

    Shiv Kumar Prajapati

  3. Molecular Biotechnology Laboratory, C.S.R.D., People’s University, Bhopal, M.P., 462037, India

    Richa Jain

  4. National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, 382355, India

    Aakanchha Jain

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  1. Kshipra Rajpoot
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Contributions

KS, SKP: experimental work, drafting.

AM: designing of experiments and performing CLSM studies, in vivo studies, drafting, editing.

RJ: in vivo pharmacodynamic studies, designing of experiments, editing and proof reading before submission.

AJ: conceptu; guidance in experiments, drafting, editing.

Corresponding author

Correspondence to Aakanchha Jain.

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Rajpoot, K., Prajapati, S.K., Malaiya, A. et al. Meropenem-Loaded Nanostructured Lipid Carriers For Skin and Soft Tissue Infection Caused by Staphylococcus aureus: Formulation, Design, and Evaluation. AAPS PharmSciTech 23, 241 (2022). https://doi.org/10.1208/s12249-022-02381-y

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