Dual Rifampicin and Isoniazid Mannose-Decorated Lipopolysaccharide Nanospheres for Macrophage- Targeted Lung Delivery.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current drug delivery Pub Date : 2023-01-01 DOI:10.2174/1567201819666220812092556

Mumuni Sumaila, Pradeep Kumar, Philemon Ubanako, Samson A Adeyemi, Yahya E Choonara

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引用次数: 1

Abstract

Background: Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity.

Methods: This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity.

Results: The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers.

Conclusion: Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.

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双重利福平和异烟肼甘露糖修饰的脂多糖纳米球用于巨噬细胞靶向肺递送。

背景:目前，结核病的治疗方案面临着一些挑战，如不一致的口服生物利用度、剂量相关的不良反应和脱靶药物毒性。方法:本研究采用溶剂注射法设计和表征了负载利福平(RIF)和异烟肼(INH)的脂质-多糖混合纳米颗粒，并展示了共轭甘露糖基残留物对巨噬细胞靶向和细胞内药物递送能力的影响。结果:该纳米球被称为甘露糖修饰的脂多糖纳米粒子，其形状为球形，平均尺寸小于120纳米。结论:总体而言，实验结果表明，甘露糖修饰的脂多糖纳米系统有望安全有效地靶向巨噬细胞递送抗结核治疗药物。

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来源期刊

Current drug delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.10

自引率

4.20%

发文量

170

期刊介绍： Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves. The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance. The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.