Dual Core-Shell Loaded Lipid-Polymer Hybrid Nanoparticles as Combination Anti-Infective Delivery Platforms

Carini, V, Scagnetti, G, Foulkes, JM, Evans, K, Saleem, I ORCID: 0000-0003-2382-6668 and Gordon, S (2025) Dual Core-Shell Loaded Lipid-Polymer Hybrid Nanoparticles as Combination Anti-Infective Delivery Platforms. Pharmaceutics, 18 (1). ISSN 1999-4923

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Abstract

Background/Objectives: The growing threat posed by antimicrobial resistance to worldwide public health highlights the urgent need not only for new anti-infective candidates, but also for innovative formulation strategies capable of mediating effective delivery of anti-infective compounds. The current study, therefore, aimed to demonstrate the feasibility of formulating lipid-polymer hybrid nanoparticles (LPHNPs) with dual loading of both core and shell compartments for combination anti-infective delivery. Methods: LPHNPs containing the antibiotic cefotaxime within a chitosan polymer core and the novel antimicrobial peptide RN7IN6 within a bacteria-mimicking lipid shell were produced by microfluidic mixing, and optimized with respect to parameters including total flow rate, flow rate ratio, and lipid concentration. Minimum inhibitory concentrations of cefotaxime and RN7IN6 co-incorporated in LPHNPs were assessed as a preliminary indicator of antibacterial efficacy. Results: Uniformly nanosized LPHNPs were produced, with maximized loading of cefotaxime and RN7IN6 within particle cores and shells, respectively. Empty LPHNPs showed an appreciable antibacterial activity, particularly against the Gram-negative bacterium Escherichia coli, while RN7IN6 was indicated to enhance cefotaxime activity against E. coli when both actives were incorporated in LPHNPs. Conclusions: The current findings clearly demonstrate the feasibility of formulating LPHNPs for core-shell co-encapsulation and delivery of anti-infectives. The promising antibacterial efficacy of co-loaded LPHNPs warrants further in-depth investigation to determine the extent of co-loaded LPHNP applications as combination anti-infective delivery platforms.
Keywords: lipid-polymer hybrid nanoparticle; bacteriomimetic; antimicrobial peptide; anti-infective; co-delivery; combination delivery; microfluidic manufacture

Item Type:	Article
Uncontrolled Keywords:	3214 Pharmacology and Pharmaceutical Sciences; 32 Biomedical and Clinical Sciences; Antimicrobial Resistance; Emerging Infectious Diseases; Bioengineering; Biotechnology; Infectious Diseases; Nanotechnology; Infection; 1115 Pharmacology and Pharmaceutical Sciences; 3214 Pharmacology and pharmaceutical sciences
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	MDPI AG
Date of acceptance:	18 December 2025
Date of first compliant Open Access:	9 January 2026
Date Deposited:	09 Jan 2026 11:06
Last Modified:	09 Jan 2026 11:06
DOI or ID number:	10.3390/pharmaceutics18010013
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27864

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