Oral delivery of biologics: Challenges and opportunities

Biologicals are currently one of the most promising avenues for therapy, and their arrival has transformed the management of a host of conditions. As large, complex molecules, biologics are extremely sensitive to the harsh conditions of the gastric environment, their favoured route of administration has mostly been parenteral. However, the convenience of administration and the low production costs of oral dosage forms coupled with the growing market for biologics has given impetus to the development of oral biologics. Not only can these make way for painless therapy, but they can also bring down the overall costs of care. Various technologies are currently under development for the oral delivery of biologics all over the world 


Barriers to oral drug delivery of biologics 

The preliminary requirement for oral biologics is the need to protect these macromolecules from the harsh environment of the gastrointestinal tract, which is acidic in nature and contains enzymes intended to break down molecules. Secondly, it is important to find a way to allow these large molecules to pass through the multiple layers lining the tract so that they are made available for systemic distribution. The main consequence of the degradation of biologic drugs on oral administration is low bioavailability. Therefore drug formulation efforts are now centred around overcoming such physicochemical challenges to enable better bioavailability. 


Novel approaches 

A host of technologies have been explored for modifying the structure of biomolecules that range from the use of polymers, nanocarriers, and their inclusion in lipid systems to permeation enhancers. 

A lot of research on lipid systems involving small molecules have already been performed. They are known to increase the permeability of biologic molecules and also protect them against hydrolysis and enzymatic degradation. Some examples of lipid systems are liposomes, archaesomes, and emulsions.  

Encapsulated biologics can also exist as nanoparticles where the drug is incorporated into tiny transporting particles and thus protected from gastric acid. At the same time, the size of nanoparticles allows for better targeting by enhanced penetration through the stomach lining. Tailored receptors that target the gastric lining can also be attached to encapsulated proteins for enhanced absorption. Polymers that are commonly used for the preparation of small-molecule drugs can be used for the preparation of such nanoparticulate formulations too. 

Another recent technique for developing oral biologics includes pills that are embedded with medicine-containing microneedles. They work by embedding themselves in the lining of the intestine and enabling the drug to penetrate the mucosal and epithelial walls. 


The way forward 

Biologics is currently one of the fastest growing categories in pharma. Delivery of these formulations orally can, in fact, be an effective way for biosimilar companies to achieve market shares by differentiating their products from innovator biologics. As several research groups are seeing promising results in the early phases of development, it however remains to be seen which ones will see the light of the day and become a clinical reality.  


1. C. Challener, “Oral Delivery of Biologic APIs: The Challenge Continues,” Pharmaceutical Technology 41 (3) 2017 
2. Nikki Withers. Alternative routes of administration – a focus on oral biologics. European Pharmaceutical Review. 28 October 2020 
3. Tony Hagen. Chasing the Holy Grail of Oral Biologics. September 9, 2020 

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