Related Experiment Video
Updated: Mar 29, 2026
08:27
Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes
Published on: August 13, 2021
5.2K
Ambient-Stable mRNA Medicines: Emerging Paradigms in Dry and Solid-State Formulation
Mohamed El-Tanani1, Syed Arman Rabbani1, Adil Farooq Wali1
1RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
Pharmaceuticals (Basel, Switzerland)
|March 28, 2026
Summary
Messenger RNA (mRNA) therapeutics face cold-chain challenges. This review explores strategies for stable mRNA formulations, aiming for room-temperature storage and global accessibility.
Area of Science:
- Biotechnology
- Pharmaceutical Sciences
- Materials Engineering
Background:
- Messenger RNA (mRNA) therapeutics offer programmable treatment options via versatile vaccination platforms.
- Widespread adoption is hindered by extreme cold storage and transportation requirements, posing a significant challenge.
- mRNA stability is a critical scientific and industrial hurdle demanding innovation in formulation and engineering.
Purpose of the Study:
- To review current knowledge and novel methods for enhancing mRNA stability and achieving cold-chain independence.
- To explore advanced mRNA development strategies and assess manufacturing, regulatory, and logistical obstacles.
- To present a pathway for developing stable mRNA medicines effective at ambient temperatures (25°C and above).
Main Methods:
- Assessment of RNA hydrolysis, lipid oxidation, and water-mediated degradation mechanisms.
- Evaluation of solid-state stabilization techniques including lyophilization, spray-freeze-drying, and thin-film technologies.
- Analysis of advanced mRNA structures (self-amplifying, circular RNA) and novel materials (nano-glass, MOFs), alongside AI-driven design.
Main Results:
- Vitrification, water replacement, and excipient-RNA interactions are key mechanisms for enhancing stability.
- Solid-state stabilization methods and advanced materials show promise for room-temperature formulations.
- Manufacturing, quality control, packaging, and environmental testing are crucial for real-world implementation.
Conclusions:
- Merging formulation design, process control, and material engineering is essential for cold-chain independent mRNA therapeutics.
- Advanced strategies and addressing logistical hurdles can enable mRNA medicines to maintain efficacy at ambient temperatures.
- Developing mRNA into a durable therapeutic platform requires integrating molecular research, process development, and regulatory standardization for global access.
Related Concept Videos
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
308
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
308
01:30Modified-Release Drug Delivery Systems: Bioavailability
108
Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
108
01:22Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence
243
Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
243
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
216
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
216
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
835
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
835
01:27Drug Delivery Systems: Different Types
235
Conventional oral drug products, termed immediate-release (IR) formulations, are engineered to promptly release their active pharmaceutical ingredient (API) upon ingestion, typically in tablets or capsules. This rapid release often results in swift drug absorption and consequent pharmacodynamic effects, although the timing and intensity can vary depending on the drug's properties. Prodrugs within these formulations require metabolic conversion to activate their pharmacodynamic effects,...
235