Recent trends in praziquantel nanoformulations for helminthiasis treatment

ABSTRACT

Introduction

Infections caused by parasitic flatworms impose a considerable worldwide health burden. Recently, World Health Organization launched its roadmap for neglected diseases for the period 2021 to 2030 and oral treatment with praziquantel (PZQ) in tablet form is the main drug therapy for combating these diseases, but its use is limited by many drawbacks, including the high therapeutic dose due to the drug’s low solubility and bioavailability. Among the strategies to improve PZQ performance, the use of drug nanocarriers has been cited as an interesting approach to overcome these pharmacological issues.

Areas covered

This review focuses on the various types of nanomaterials (polymeric, lipidic, inorganic nanoparticles, and nanocrystals) which have been recently used to improve PZQ therapy. In addition, recent advances in PZQ nanoformulations, developed to overcome the barriers of the conventional drug are described.

Expert opinion

Considering the poor rate of discovery in the anthelmintic segment observed in recent decades, the effective management of existing drugs has become essential. The application of new strategies based on nanotechnology can extend the useful life of PZQ in new and more effective formulations. Pharmaceutical nanotechnology can solve the pharmacokinetic challenges characteristic of PZQ and improve its solubility and bioavailability.

KEYWORDS:

• Nanomedicine
• nanotechnology
• helminthiasis
• schistosomiasis
• parasitic diseases
• nanoformulation
• nanomaterials
• oral formulation
• pediatric formulation
• drug discovery

Article highlights

• Parasitic worms infect more than a quarter of the population of the world, and negatively affect the nutritional status and development of children and women, which can lead to chronic ill-health and death.

• Chemotherapy is the main control method for infections caused by flatworms. Since its discovery in the 1970s, PZQ has replaced many other drugs as the sole treatment for a range of flatworm infections in humans and animals worldwide.

• Recently, the WHO launched its roadmap for neglected diseases for the period 2021 to 2030, which aims to increase prevention and control of neglected diseases such as schistosomiasis, foodborne trematodiases, taeniasis, and cysticercosis.

• Oral treatment with PZQ in tablet form is the main drug therapy for combating infections caused by flatworms, but its use is limited by many drawbacks, including the high therapeutic dose due to the drug’s low solubility and bioavailability as well as its rapid hepatic metabolism, resulting in a short half-life of PZQ in the circulation.

• PZQ was included in the WHO Model List of Essential Medicines for Children, but the absence of an adapted oral formulation for the youngest children is an obstacle in preventive chemotherapy.

• PZQ has low solubility due to its physical-chemical characteristics, which affect its form of presentation and absorption.

• Among the strategies to improve PZQ performance, the use of drug nanocarriers has been cited as an interesting approach by which to overcome these pharmacological issues.

• In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Different types of PZQ nanosystems have been investigated as nanocarriers for the treatment of helminthiasis.

• Various types of nanoparticle systems were developed for drug delivery by academic research groups rather than by industry, and this has resulted in a variety of nano PZQ formulations, which might serve as starting points for more efficient helminthiasis control.

• Most articles reporting the use of nanocarriers and PZQ are composed of lipid or polymeric nanostructures, mainly using S. mansoni as an experimental model.

• Regarding therapeutic efficacy, the different types of PZQ nanosystems showed an enhanced significant anthelmintic effect compared to standard PZQ.

• Colloidal delivery systems can maintain the stability of the nano-formulated PZQ, when administered orally, and thus enhance the bioavailability of the administered drug.

• Although nanocrystals makes it possible to improve the solubility of PZQ, it has been reported that this type of nanocarrier can have certain stability complications, which may compromise the capacity to ensure a consistent dosage.

• Nanomaterials based on inorganic particles are non-toxic, hydrophilic, biocompatible, and highly stable compared to organic materials. These inorganic particles have gained significant attention in preclinical studies as potential therapeutic systems for schistosomiasis.

• Despite the enormous efforts made in developing nanoparticles as drug-delivery systems for helminthiases using PZQ, none has been approved for that purpose yet.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) under Grant [number 2019/25905-2 (ACM) and 2020/01441-4 (JdM)].