Natural barriers to drug administration protect the body from foreign substances or micro-organisms while significantly impairing the distribution and therapeutic targeting of medicines to specific tissues or organs. Understanding how to bypass them is essential for addressing several drug delivery challenges faced while developing therapeutical treatments.

This article will discuss the primary biological and physical barriers to drug administration and explore the challenges and solutions offered by modern drug delivery systems, particularly nanosystems, in overcoming these obstacles. These advanced systems are specifically designed to bypass the barriers of drug distribution, offering new possibilities for effective disease management.

 

The Barriers to Drug Administration

 

Physical barriers to drug administration constitute the first line of defense. The skin, the body’s largest organ, with its stratified, keratinized epithelium, is a robust barrier to transdermal drug delivery [1]. Similarly, the epithelial lining of the gastrointestinal tract hinders the absorption of orally administered drugs due to its tight junctions and efflux pumps that actively expel foreign substances [2]. Other examples of mucosal membrane barriers are the respiratory tract and the nasal passages. 

Biological barriers to drug administration involve more complex biological systems and cellular mechanisms. The blood-brain barrier (BBB), composed of tightly packed endothelial cells, selectively permits the passage of substances into the brain, effectively protecting neural tissue and restricting the delivery of many potential treatments for central nervous system disorders or cerebral cancers [3]. Additionally, mucosal barriers in the respiratory, gastrointestinal, and urogenital tracts present selective permeability that limits drug uptake, as well as eye-protecting barriers, like the corneal epithelium and conjunctival membranes. Similarly, the blood-testis and placental barriers regulate the internal environments of the testes and the fetus, respectively, affecting drug delivery to these areas [4].

These structures are critical in controlling the penetration and absorption of therapeutic agents, representing highly significative barriers of drug distribution and significant drug delivery challenges.

Additionally, cell membranes are difficult to overcome for big and charged biomolecules, such as proteins, antibodies, and nucleic acids that need to reach their intracellular targets. 

 

Challenges for Drug Delivery Systems and How Nanotechnology Can Help to Overcome Them

 

Nanosystems such as nanoparticles and lipid nanoemulsions have faced drug delivery challenges by enhancing therapeutic agents’ bioavailability, safety, and efficacy. These systems are designed to overcome biological barriers to drug administration that represent an obstacle to traditional treatments, enabling targeted drug delivery and controlled release, bypassing, thus, barriers of drug distribution.

Despite the challenges faced, some nanosystems have demonstrated significant therapeutic success in patients thanks to their ability to overcome drug delivery barriers.

Cyclosporine, a potent immunosuppressive agent, is commonly used to treat chronic dry eye disease. However, its hydrophobic nature makes ocular delivery challenging due to the natural barriers that protect the eye and its aqueous environment. A specific lipidic nanoemulsion formulation of cyclosporine, commercially known as Restasis®, facilitates the integration of cyclosporine into the ocular tissues by incorporating it within the lipid layers of the tear film. Patients receiving this treatment showed a marked improvement in tear production and reduced corneal damage due to dry eye [5,6].

The administration of antiretroviral drugs in HIV treatment is limited by their poor cellular uptake and impaired ability to cross the BBB to reach viral reservoirs within the central nervous system. A lipidic nanoemulsion formulation was developed for antiretroviral drugs to enhance their delivery across these barriers. The clinical trials demonstrated that the nanoemulsion could effectively deliver higher concentrations of antiretroviral drugs to the brain, leading to better viral suppression in this hard-to-reach area, where HIV can hide from standard treatments [7,8].

Another example of how nanotechnology can overcome physical barriers, as well as biological ones, is represented by Estrasorb®, a topical micellar nanoparticle estradiol emulsion approved for symptomatic menopausal women in hormone replacement therapy. The nanoparticle formulation enhances the drug’s ability to penetrate the skin barrier, facilitating systemic absorption through the dermal route, which avoids the gastrointestinal metabolism that oral formulations typically undergo [9,10].

A more well-known example of innovative gene therapy is Onpattro®, which was approved in August 2018 by the Food and Drug Administration (FDA). Onpattro® is a lipid nanoparticle-based short interfering RNA (siRNA) drug for treating polyneuropathies induced by hereditary transthyretin amyloidosis. Onpattro® represents a clear example of using nanotechnology to overcome biological barriers. The lipid nanoparticle formulation protects siRNA stability and allows the delivery of it to the cytoplasm of hepatocytes in vivo, bypassing the cell membrane, following intravenous administration [11]. 

These examples demonstrate the diverse applications of lipidic nanosystems in overcoming biological barriers to drug administration, especially in treating diseases with challenging delivery requirements.

 

DIVERSA Offers Solutions to Help your Molecule Cross Biological Barriers

 

At DIVERSA, our mission is to provide easy-to-use solutions to face drug delivery challenges through our innovative lipidic nano-carriers. 

Our R&D efforts and know-how have led to the development of biocompatible lipid nanosystems, whose delivery and ability to bypass biological barriers are comparable to already approved lipid nanoparticles for clinical application. They are designed to effectively deliver different types of cargo, including small molecules, peptides, proteins, and nucleic acids, with a highly customizable approach to your specific application.

We aim to democratize nanotechnology. Our technology is available to the entire scientific community in a ready-to-use format. Its delivery efficacy is comparable to already approved lipid nanoparticles for clinical application. There are specific references for each type of molecule and also fluorescent options that allow tracking.

We also collaborate with other companies to develop tailored formulations. If you do not find the DIVERSA reagent that completely suits your research, we will build a specific project for your specific molecule. We tailor our technology to your needs with our co-development program, offering personalized lipid-based nanosystems designed to overcome the specific limitations of your molecule.

 

Do you want to know how our technology can help your molecule to bypass biological barriers? Contact us!

 

References

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