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One Platform Comparison of Polymeric and Lipidic Nanoparticles for the Delivery of Amphotericin B

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Abstract

Amphotericin B (AmB) is a membrane-acting antibiotic used for the treatment of fungal and protozoal infections. AmB exists in various molecular forms, i.e., monomeric, super-aggregated, and oligomeric forms, where oligomeric forms are highly toxic because of their relative affinity toward cholesterol present over human cell membrane. Hence, the objective of our research work was to study the aggregation state of AmB in two different nanoformulations, i.e., solid lipid nanoparticles (SLNs) and zein-based nanoparticles (PNPs), with the aim of enhancing the fraction of less toxic form of AmB, and a comparative study was performed. The zein and glyceryl monostearate can intercalate the polyenic domain of AmB and thereby hinder the hydrophobic attractions between the AmB molecules, which allows their existence in monomeric forms. The particle size of AmB-SLNs and AmB-PNPs were 378.90 ± 9.50 nm and 184.90 ± 6.00 nm, while zeta potential was −34.97 ± 0.51 mV and +28.93 ± 2.29 mV, respectively. In vitro release studies showed more controlled release of AmB from PNPs (52.48 ± 1.07%) as compared to SLNs (86.33 ± 0.93%). The predominant aggregation state of AmB in both formulations was determined by UV–visible and circular dichroism spectrophotometry, where a higher degree of monomerization of AmB was reported in AmB-SLNs as compared to AmB-PNPs. Toxicity of the nanoformulations was evaluated through hemolysis test, where the results suggested that AmB-SLNs and AmB-PNPs were less hemolytic as compared to pure AmB. The nanoformulations demonstrated the predominant monomeric form of AmB, which may offer higher selectivity index toward microbial membrane.

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Data Availability

The authors confirm that all the data supporting the findings of this study are presented within the article. Also, raw data that support the findings of this research may provided upon reasonable request.

Abbreviations

% CDR:

Cumulative drug release

AmB:

Amphotericin B

CD:

Circular dichroism spectroscopy

DL:

Drug loading

DLS:

Dynamic light scattering

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FTIR:

Fourier-transform infrared spectroscopy

GMS:

Glyceryl monostearate

PBS:

Phosphate buffer saline

PDI:

Polydispersity index

PNPs:

Polymeric nanoparticles

RDI:

Redispersibility index

RH:

Relative humidity

SD:

Standard deviation

SEM:

Scanning electron microscopy

SLNs:

Solid lipid nanoparticles

SL:

Soy lecithin

TDW:

Triple-distilled water

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Acknowledgements

The authors thank the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Government of India for providing facilities to write this research article. A.P. is thankful to Indian council of Medical Research (ICMR), New Delhi for the financial support in the form of JRF under the ICMR Extramural Research Project (Project ID: 2020-4686; Ref. No. 5/13/34/2020/NCD-III).

Funding

The National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Department of Pharmaceuticals, Ministry of Chemical and Fertilizers, Government of India, provided financial assistance (683/MS-PE/2020).

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Authors and Affiliations

  1. Drug Delivery and Nanomedicine Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) - Raebareli, Lucknow, Uttar Pradesh, 226002, India

    Nandha Joyson, Anchal Pathak & Keerti Jain

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  1. Nandha Joyson
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  2. Anchal Pathak
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  3. Keerti Jain
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Contributions

K.J. contributed to the conceptualization and supervision and helped to manage resources. Data curation, investigation, and formal analysis were performed by J.N. A.P. contributed to validation, and review and editing.

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Correspondence to Keerti Jain.

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The authors clarify that the formulation part of this research work has been filed for Indian patent at Indian Patent Office (IPO), Mumbai, India; Application No.: 202311071032; Date of Application: 18/10/2023.

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Joyson, N., Pathak, A. & Jain, K. One Platform Comparison of Polymeric and Lipidic Nanoparticles for the Delivery of Amphotericin B. AAPS PharmSciTech 24, 226 (2023). https://doi.org/10.1208/s12249-023-02672-y

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