Recent advances in nanoformulation development of Ritonavir, a key protease inhibitor used in the treatment of HIV-AIDS

ABSTRACT

Introduction

AIDS is one of the world’s most serious public health challenges. Protease inhibitors are key components of AIDS treatment regimen. Ritonavir is a well-known protease inhibitor with low aqueous solubility belonging to BCS class II category. Some of the severe adverse effects associated with this drug restricted its use in the treatment of AIDS. However, several attempts were made by researchers in the past to enhance the oral bioavailability of Ritonavir.

Areas covered

The current review mainly focuses on the adverse effects of Ritonavir and recent approaches followed by researchers on the development of nanoformulations of Ritonavir. Further, various patents filed on Ritonavir have also been discussed in the current review.

Expert opinion

Most research on nanoformulation development for Ritonavir is mainly focused on enhancing the solubility and oral bioavailability of the drug. Some of the researchers focused on the lymphatic targeting of the drug in order to bypass the hepatic metabolism of the drug. However, most of the research topics did not cover the toxicity evaluation of the developed formulation. Since the major issue of Ritonavir is not only oral bioavailability but also drug-induced toxicity, this area needs to be considered during the formulation development.

KEYWORDS:

• AIDS
• hepatotoxicity
• HIV
• protease inhibitors
• ritonavir

Article highlights

• HIV-AIDS is one of the severe health care issues across the globe

• Ritonavir is a protease inhibitor that belongs to BCS class II category

• Ritonavir is associated with poor oral bioavailability and adverse effects such as hepatotoxicity and cardiotoxicity

• Formulations targeting lymphatic system would help in avoiding hepatic-first pass metabolism to enhance bioavailability

• Polymeric nanoparticles and lipid based nano formulations enhance oral bioavailability of poorly water-soluble drugs

• Formulations that would reduce drug induced toxicity is the key area to be focused upon

Acknowledgments

The authors are thankful to Indian Council of Medical Research (ICMR), New Delhi, India for providing financial assistant to Srinivas Reddy Jitta in the form of Senior Research Fellowship (SRF) (project Ref. no. 45/73/2018-Nan/BMS, dated 4 June 2019). The authors are thankful to the Department of Pharmaceutics of Manipal College of Pharmaceutical Sciences (MCOPS) and Manipal Academy of Higher Education (MAHE), Manipal, Karnataka- 576104 for providing the conveniences to carry out the research work in this area of research.

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 paper was not funded.