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Journal Article Review Epublish 2 citations

PubMed: 40430843 DOI: 10.3390/pharmaceutics17050550

A Review on the Stability Challenges of Advanced Biologic Therapeutics.

Pharmaceutics 17(5)

Authors: Sruthi Sarvepalli, Shashank Reddy Pasika, Vartika Verma, Anusha Thumma, Sandeep Bolla, Pavan Kumar Nukala, Arun Butreddy, Pradeep Kumar Bolla

Affiliations

  • College of Pharmacy and Health Sciences, St John's University, Queens, New York, NY 11439, USA.
  • Department of Biotechnology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Raebareli 226002, India.
  • Laboratory of Translational Research in Nanomedicines, Lifecare Innovations Private Limited, Lucknow 226021, India.
  • Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
  • Department of Statistical Programming, Fortrea, Durham, NC 27709, USA.
  • Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
  • Department of Biomedical Engineering, College of Engineering, The University of Texas at El Paso, El Paso, TX 79968, USA.

Abstract

Advanced biotherapeutic systems such as gene therapy, mRNA lipid nanoparticles, antibody-drug conjugates, fusion proteins, and cell therapy have proven to be promising platforms for delivering targeted biologic therapeutics. Preserving the intrinsic stability of these advanced therapeutics is essential to maintain their innate structure, functionality, and shelf life. Nevertheless, various challenges and obstacles arise during formulation development and throughout the storage period due to their complex nature and sensitivity to various stress factors. Key stability concerns include physical degradation and chemical instability due to various factors such as fluctuations in pH and temperature, which results in conformational and colloidal instabilities of the biologics, adversely affecting their quality and therapeutic efficacy. This review emphasizes key stability issues associated with these advanced biotherapeutic systems and approaches to identify and overcome them. In gene therapy, the brittleness of viral vectors and gene encapsulation limits their stability, requiring the use of stabilizers, excipients, and lyophilization. Keeping cells viable throughout the whole cell therapy process, from culture to final formulation, is still a major difficulty. In mRNA therapeutics, stabilization strategies such as the optimization of mRNA nucleotides and lipid compositions are used to address the instability of both the mRNA and lipid nanoparticles. Monoclonal antibodies are colloidally and conformationally unstable. Hence, buffers and stabilizers are useful to maintain stability. Although fusion proteins and monoclonal antibodies share structural similarities, they show a similar pattern of instability. Antibody-drug conjugates possess issues with conjugation and linker stability. This review outlines the stability issues associated with advanced biotherapeutics and provides insights into the approaches to address these challenges.

MeSH

Cells, Genes, Antibodies, Nanoparticles, Pharmaceutical Preparations, Antibodies, Monoclonal, Therapeutics, Lipid Nanoparticles