Nanoemulsions delivering antimalarial oligonucleotides

Unlock Malaria Treatment: Nanoemulsions and Oligonucleotides - A Promising Duo

"Discover how validated spectrophotometric methods are revolutionizing antimalarial drug delivery using nanoemulsions and oligonucleotides for targeted treatment."


Malaria remains a devastating global health issue, affecting hundreds of millions annually. The rise of drug-resistant parasites has intensified the challenge, demanding innovative therapeutic strategies.

Oligonucleotides, single-stranded nucleic acids, have emerged as a promising approach, capable of interfering with protein synthesis and inhibiting parasite growth. However, their effectiveness is limited by poor cell penetration and vulnerability to nuclease degradation.

To overcome these obstacles, researchers are exploring the use of positively-charged colloidal carriers, specifically oil-in-water (o/w) nanoemulsions, to deliver oligonucleotides. These nanoemulsions spontaneously interact with nucleic acids, forming protective polyionic complexes that enhance cell uptake and prevent degradation.

How Spectrophotometry Validates Oligonucleotide Delivery via Nanoemulsions

Nanoemulsions delivering antimalarial oligonucleotides

A key challenge is accurately measuring how well oligonucleotides associate with these nanoemulsions. Due to the tiny size of the oil droplets, traditional methods are difficult to apply. Most approaches rely on indirect measurements, calculating the difference between the initial drug amount and the free drug found after separating the water phase using ultrafiltration.

This study validates a spectrophotometric method for estimating oligonucleotide association with cationic nanoemulsions. This method analyzes phosphodiester and phosphorothioate oligonucleotides—targeting Plasmodium falciparum topoisomerase II—at 262 nm. The validation process confirms the method's specificity, linearity, accuracy, and precision.

  • Specificity: Confirmed by comparing the absorption spectra of oligonucleotide solutions with solutions containing glycerol, ensuring no interference.
  • Linearity: Demonstrated over a concentration range of 0.4 to 1.0 nmol/mL, with a high correlation coefficient (r > 0.998).
  • Precision: High repeatability (intra-day) and intermediate precision (inter-day), with relative standard deviation values below 2.6%.
  • Accuracy: Recoveries ranged from 98.8 to 103.6%, indicating excellent agreement between added and measured amounts.
The method also assesses oligonucleotide recovery through 30 kDa membranes. Results show over 92% recovery, confirming minimal binding to the ultrafiltration membranes. This reliable method supports the evaluation of nanoemulsion composition and optimization for effective oligonucleotide delivery.

The Future of Malaria Treatment

This validated spectrophotometric method provides a reliable tool for estimating oligonucleotide association with nanoemulsions, crucial for optimizing antimalarial drug delivery systems. The method is linear, specific, precise, and accurate, paving the way for developing more effective treatments against drug-resistant malaria. Ongoing research focuses on refining intravenous nanoemulsions for antimalarial oligonucleotide delivery, promising a new era in malaria therapeutics.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1590/s0100-40422011000900026, Alternate LINK

Title: Validation Of A Spectrophotometric Method To Estimate The Adsorption On Nanoemulsions Of An Antimalarial Oligonucleotide

Subject: General Chemistry

Journal: Química Nova

Publisher: FapUNIFESP (SciELO)

Authors: Fernanda Bruxel, Silvia S Guterres, Helder F Teixeira

Published: 2011-09-01

Everything You Need To Know

1

How do nanoemulsions improve the effectiveness of oligonucleotides in malaria treatment?

Nanoemulsions are used as positively-charged colloidal carriers designed to deliver oligonucleotides. These oil-in-water nanoemulsions spontaneously interact with nucleic acids, forming protective polyionic complexes. This enhances cell uptake and protects the oligonucleotides from nuclease degradation, improving their effectiveness against malaria parasites. Without nanoemulsions, oligonucleotides would be less effective due to poor cell penetration and vulnerability to being broken down.

2

How is spectrophotometry used to validate the delivery of antimalarial oligonucleotides using nanoemulsions?

Spectrophotometry is used to validate the effectiveness of nanoemulsions in delivering antimalarial oligonucleotides. Specifically, it is used to accurately measure how well oligonucleotides associate with nanoemulsions by analyzing phosphodiester and phosphorothioate oligonucleotides at 262 nm. The method's specificity, linearity, accuracy, and precision are validated to ensure reliable measurements, which is critical for optimizing nanoemulsion composition and delivery.

3

What are oligonucleotides and how are they intended to combat malaria?

Oligonucleotides are single-stranded nucleic acids that interfere with protein synthesis, thereby inhibiting parasite growth. In the context of malaria treatment, phosphodiester and phosphorothioate oligonucleotides are designed to target *Plasmodium falciparum* topoisomerase II. Their use is limited by poor cell penetration and vulnerability to nuclease degradation, which is why they are delivered via nanoemulsions to enhance their effectiveness.

4

What key parameters were validated to ensure the reliability of the spectrophotometric method, and why is each important?

The spectrophotometric method was validated based on several key parameters. Specificity was confirmed by ensuring no interference from substances like glycerol. Linearity was demonstrated over a concentration range of 0.4 to 1.0 nmol/mL, with a high correlation coefficient. Precision was validated through repeatability and intermediate precision, with low relative standard deviation values. Accuracy was confirmed through recoveries ranging from 98.8 to 103.6%. These validations ensure the method's reliability in estimating oligonucleotide association with nanoemulsions. Without these steps there would be no quality control.

5

What are the broader implications of using validated spectrophotometric methods to assess nanoemulsions for oligonucleotide delivery in the fight against malaria?

The use of validated spectrophotometric methods to assess nanoemulsions for oligonucleotide delivery has significant implications for combating drug-resistant malaria. It allows researchers to optimize nanoemulsion composition and delivery, leading to more effective treatments. By providing a reliable tool for measuring oligonucleotide association, it accelerates the development of new antimalarial drugs and strategies. The successful application of this method could usher in a new era of malaria therapeutics, particularly in addressing the challenges posed by drug-resistant parasites.

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