In recent decades, many diseases have emerged, and advanced scientific research has developed numerous medicines to treat or mitigate these conditions. The concept of medicine dates back to medieval times when treatments were derived directly from nature, using leaf extracts either ingested or applied to wounds. Our ancestors, through trial and error, identified key plants with medicinal properties, and this knowledge has been passed down through the centuries.

In the 20th century, modern science began to evolve rapidly, taking inspiration from nature to create new medicines. Most medicines are composed of carbon, hydrogen, and oxygen skeletons, with a molecular weight of less than 1000 Da , which allows them to be well-absorbed and administered in pill form. However, recent advancements have shown that pills are sometimes inadequate for reducing disease states. This has led to the development of new modalities like proteins and antibodies, which have generated significant interest in the medical field.

These new technologies are particularly effective in treating deadly diseases such as cancer and rare conditions. However, the biggest disadvantage is that these treatments can only be administered intravenously (IV) because their large size prevents effective absorption when taken orally. The digestive process often breaks down these drugs, rendering them less effective. As of August 2024, over 1,700 oral drugs have been approved by the FDA. This figure encompasses a wide array of medications for various conditions, including both novel therapies and generic formulations.

The FDA consistently approves new oral drugs ( formulated in to pills), with multiple approvals each month, reflecting ongoing advancements in pharmaceutical research and development. For instance, in 2024 alone, dozens of new oral drugs have been approved for conditions such as cancer, autoimmune diseases, and neurological disorders. Globally, more than 10,000 pharmaceutical companies are actively engaged in researching and developing small molecule pharmaceuticals. These companies span all stages of drug development, from research and development to manufacturing and distribution. Overall, thousands of small molecules are currently under investigation in clinical trials, with databases like ClinicalTrials.gov listing over 20,000 ongoing trials involving small molecules across all phases of development.

Although pills can be taken by oneself, IV administration requires a specialized nurse to inject and can't be done independently. It also requires training and is not convenient to implement, especially with elderly people. However, one advantage of IV administration over pills is that it delivers medication directly into the bloodstream, causing immediate action to reduce the disease state. Pills, on the other hand, involve small molecules that take longer to take effect. In the mid-2000s, there was an active trial where companies tried to convert large molecules into pill form by packaging them tightly in capsules and attempting to deliver them to the lungs as inhalers.

The outcome was detrimental since lungs have many receptors that are prone to recognizing various foreign objects, including drugs. This led to lung inflammation. After observing these results, the pharmaceutical companies promptly discontinued the research. However, recent advancements in the field of formulation have led to significant progress. In a landmark effort, the FDA approved Pulmozyme as the first protein drug for lung disease, representing a class of large molecules.1 Currently, more than ten inhaled protein therapeutics are being assessed in clinical trials for the treatment of various lung diseases, including asthma, cystic fibrosis, lung cancer, COPD, and COVID-19.

Pills typically consist of small molecules with an overall molecular weight of less than 1000 Da. Most IV treatments consist of larger molecules between sizes ~ 3,000-150,000 Da. The recombinant IgG1μtp and IgG3μtp anti-G antibodies ranged from 150,000 to 1,000,000 Da in molecular weight. Anti-RhD antibodies (anti-D) are crucial for the prevention of haemolytic disease of the fetus and newborn (HDFN) caused by RhD incompatibility.

References

1 Matthews AA, Ee PLR, Ge R. Developing inhaled protein therapeutics for lung diseases. Mol Biomed. 2020;1(1):11. doi: 10.1186/s43556-020-00014-z. Epub 2020 Oct 30. PMID: 34765995; PMCID: PMC7595758.