Advances in nasal delivery of antibiotics

In a recent study published in the Journal of Drug Delivery Science and Technology, researchers reviewed the advances and challenges in the intranasal delivery of antibiotics.

Antibiotics are substances that act against bacteria to prevent or treat infectious diseases. Notably, the overuse of antibiotics contributes to the growing bacterial resistance. Consequently, oral administration of antibiotics has been prevalent and preferred. Nevertheless, oral administration could result in adverse effects upon systemic distribution. Therefore, the route of antibiotic administration is critical to augment bioavailability and minimize undesirable adverse outcomes and the risk of resistance.

The nasal administration of antibiotics could be paramount for upper respiratory tract infections. Intranasal administration is non-invasive and offers several advantages, such as the rapid onset of action, ease of application, and local and systemic availability. In the present review, researchers discussed various approaches for the intranasal administration of antibiotics.

Review article - Nasal route for antibiotics delivery: Advances, challenges and future opportunities applying the quality by design concepts. Image Credit: Josep Suria / ShutterstockReview article - Nasal route for antibiotics delivery: Advances, challenges and future opportunities applying the quality by design concepts. Image Credit: Josep Suria / Shutterstock

Nasal drug delivery mechanism

The nasal cavity is primarily used to treat the upper respiratory tract illnesses such as nasal/lung infections, sinusitis, allergic rhinitis, and congestion. The meatus is the best region for local treatment as it is connected to sinus openings. Any locally acting drug requires a longer residence time, and smaller doses could be used for direct administration at the site of action.

The respiratory region is the largest area of nasal passages with vascularized mucosa and is pivotal for the systemic absorption of drugs. In addition, nasal arterial blood supply, mainly through sphenopalatine, ophthalmic, and facial arteries, is essential for systemic absorption. Besides, systemic absorption also facilitates drug entry into the brain parenchyma via the blood-brain barrier (BBB).

As such, it could alleviate the systemic side effects of the central nervous system (CNS)-acting agents. The other possible mechanisms of drug entry into the brain include the olfactory and trigeminal nerve pathways. Intranasal administration could circumvent the two critical challenges in drug delivery to the brain –hepatic metabolism and the BBB.

Limitations of nasal administration

Nasal mucociliary clearance limits the drug residence time in the nasal cavity and reduces drug permeability through the nasal mucosa. Besides, enzymatic degradation and transporter proteins are significant barriers to drug bioavailability. Efflux systems and transporters are crucial for drug absorption and distribution into the CNS and systemic circulation. Additionally, several enzymes in the nasal passages impact drug metabolism.

Nasally-administered antibiotics

Multiple antibiotics have been tested for nasal delivery. These include mupirocin, gentamicin, vancomycin, ciprofloxacin, polymyxin B, thiamphenicol, rifamycin, azithromycin, and doxycycline, among others. One study reported that intranasal gentamicin solution, given as drops in sodium glycolate or individually, was well-tolerated and efficacious in humans.

Another study showed that intranasal irrigation of mupirocin in normal saline effectively reduced the numbers of Staphylococcus aureus in the maxillary sinus. Similarly, nasal irrigation using vancomycin has been applied for sinonasal polyposis. Furthermore, intranasal delivery devices have been created to enhance clinical outcomes.

Optimization of intranasal antibiotic administration

Quality by design (QbD) is a knowledge- and risk-based tool for quality management in pharmaceutical development. The QbD methodology includes examining the quality target product profiles (QTPPs), identifying critical quality attributes (CQAs) of the products, and risk assessment (RA). 

Applying these QbD concepts may offer logical ways to design the best formulation strategies in the early development to optimize antibiotic delivery upon nasal administration. The QTPP parameters for intranasal antibiotics are chiefly linked to the product’s ability to be retained in the nasal cavity, avoiding mucociliary clearance and releasing the drug (distribution profile).

The CQAs are physical, biological, microbiological, or chemical characteristics that influence the quality of the final product. For example, the CQA parameters for intranasal antibiotics affect adhesion, stability, distribution, dissolution, permeability, and solubility. Among the various innovative approaches developed for the intranasal delivery of antibiotics, in situ gels are the most promising.

In situ gels exhibit sol-to-gel transition in response to external stimuli and offer sustained release profile, prolonged retention time, and higher nasal absorption. The gelation mechanism depends on the polymer type, and in general, three types of polymers are used in these gels – thermo-, ionic, and pH-sensitive polymers. These polymers facilitate sol-to-gel transition based on changes in physiological conditions.

Concluding remarks

Appropriate use of antibiotics is vital to minimize the risk of resistance. This could be achieved through innovations in drug formulations and delivery. As such, the nasal route of administration is advantageous in treating local, systemic, and brain infections. Together with the application of QbD concepts and in situ gels, the intranasal delivery of drugs could increase the effectiveness and retention time of antibiotics and, thereby, reduce the risk of antibiotic resistance.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.


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