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Low Density Lipid Nanoparticles for Solid Tumor Targeting.

Mayank Shrivastava¹, Aviral Jain¹, Arvind Gulbake¹

¹Pharmaceutics Research Project Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (M. P.), India.

Scientia Pharmaceutica

|August 18, 2015

Summary

New low-density lipid nanoparticles (LDLN) loaded with 5-Fluorouracil (5-FU) effectively target solid tumors. These LDLN show enhanced tumor accumulation and significant tumor growth suppression, offering a promising cancer therapy approach.

Keywords:

5-Fluorouracil Apo protein 100 LDL receptors Lipoproteins

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A Comprehensive Procedure to Evaluate the In Vivo Performance of Cancer Nanomedicines

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Area of Science:

Biomedical Engineering
Nanotechnology
Oncology

Background:

Cancer cells exhibit rapid proliferation and overexpress low-density lipoprotein (LDL) receptors, creating a target for selective drug delivery.
5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent with limitations in targeted delivery.
Developing targeted delivery systems is crucial for improving cancer treatment efficacy and reducing side effects.

Purpose of the Study:

To develop and characterize 5-Fluorouracil (5-FU)-encapsulated low-density lipid nanoparticles (LDLN) for targeted cancer therapy.
To evaluate the in vitro drug release profile of the prepared LDLN.
To assess the in vivo biodistribution, pharmacokinetics, and tumor growth suppression efficacy of 5-FU-loaded LDLN.

Main Methods:

Preparation of 5-FU-loaded LDLN using the emulsion congealing method, mimicking plasma-derived LDL with apolipoprotein B-100.
Characterization of LDLN particle size (161±3.5 nm) and morphology (spherical) using transmission electron microscopy (TEM).
In vitro drug release studies, in vivo serum concentration and biodistribution analysis, and tumor growth suppression studies in a relevant model.

Main Results:

Prepared LDLN exhibited a particle size of 161±3.5 nm, spherical shape, and a drug content of 0.370±0.05 mg/mL.
In vitro studies demonstrated a sustained release profile of 5-FU from LDLN over time.
In vivo studies showed significant tumor accumulation (8.5% 5-FU) with minimal liver uptake (2.1%) at 24 hr, leading to 89.76% reduction in tumor height compared to controls.

Conclusions:

The prepared 5-FU-loaded LDLN effectively target solid tumors through active uptake via LDL receptors mediated by apolipoprotein B-100.
LDLN demonstrate potential for enhanced delivery of 5-FU to tumors, resulting in significant tumor growth inhibition.
This targeted nanoparticle approach holds promise for improving the therapeutic index of 5-FU in cancer treatment.