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Advances in nasal antibiotic administration
In a recent study published in the Journal of Drug Delivery Science and Technology, researchers examined the advances and challenges in intranasal antibiotic delivery. Antibiotics are substances that work against bacteria to prevent or treat infectious diseases. In particular, the excessive use of antibiotics contributes to growing bacterial resistance. Therefore, oral administration of antibiotics is predominant and preferred. However, oral administration could have negative effects on systemic distribution. Therefore, the route of antibiotic administration is crucial to increase bioavailability and minimize unwanted side effects and the risk of resistance. Nasal administration...
Advances in nasal antibiotic administration
In a recently published study in the Journal of Drug Delivery Science and Technology Researchers examined the advances and challenges in intranasal antibiotic delivery.
Antibiotics are substances that work against bacteria to prevent or treat infectious diseases. In particular, the excessive use of antibiotics contributes to growing bacterial resistance. Therefore, oral administration of antibiotics is predominant and preferred. However, oral administration could have negative effects on systemic distribution. Therefore, the route of antibiotic administration is crucial to increase bioavailability and minimize unwanted side effects and the risk of resistance.
Nasal administration of antibiotics could be of utmost importance in upper respiratory tract infections. Intranasal administration is non-invasive and offers several advantages such as: B. the rapid onset of action, the easy application and the local and systemic availability. In the present review, researchers discussed various approaches to intranasal administration of antibiotics.
Nasal drug delivery mechanism
The nasal cavity is primarily used to treat upper respiratory diseases such as nasal/lung infections, sinusitis, allergic rhinitis, and nasal congestion. The ear canal is the best region for local treatment because it is connected to the 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 the nasal passages with vascularized mucosa and is crucial for the systemic absorption of drugs. In addition, the nasal arterial blood supply, mainly via the sphenopalatine, ophthalmic and facial arteries, is essential for systemic absorption. In addition, systemic absorption also facilitates drug entry into the brain parenchyma across the blood-brain barrier (BBB).
As a result, it could alleviate the systemic side effects of agents that act on the central nervous system (CNS). Other possible mechanisms of drug entry into the brain include the olfactory and trigeminal nerve pathways. Intranasal administration could circumvent the two key challenges in drug delivery to the brain – liver metabolism and the blood-brain barrier.
Limitations of nasal administration
Nasal mucociliary clearance limits drug residence time in the nasal cavity and reduces drug permeability through the nasal mucosa. Furthermore, enzymatic degradation and transport proteins are significant barriers to drug bioavailability. Efflux systems and transporters are crucial for drug absorption and distribution in the CNS and systemic circulation. In addition, several enzymes in the nasal passages influence drug metabolism.
Nasally administered antibiotics
Several antibiotics have been tested for nasal administration. These include mupirocin, gentamicin, vancomycin, ciprofloxacin, polymyxin B, thiamphenicol, rifamycin, azithromycin and doxycycline. One study reported that intranasal gentamicin solution, administered as drops in sodium glycolate or individually, was well tolerated and effective in humans.
Another study showed that intranasal irrigation of mupirocin in normal saline was effective in reducing the number of Staphylococcus aureus in the maxillary sinus. Similarly, nasal irrigation with vancomycin has been used for sinonasal polyposis. In addition, intranasal delivery devices have been developed to improve 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 the study of quality target product profiles (QTPPs), identification of critical quality attributes (CQAs) of the products and risk assessment (RA).
Applying these QbD concepts may provide logical opportunities to develop the best formulation strategies in early development to optimize antibiotic delivery when administered nasally. The QTPP parameters for intranasal antibiotics are mainly related to the ability of the product to be retained in the nasal cavity, avoid mucociliary clearance and release the active ingredient (distribution profile).
The CQAs are physical, biological, microbiological or chemical properties that influence the quality of the end product. For example, the CQA parameters for intranasal antibiotics affect adhesion, stability, distribution, dissolution, permeability and solubility. Among the various innovative approaches developed for intranasal antibiotic delivery, in situ gels are the most promising.
In situ gels exhibit a sol-to-gel transition in response to external stimuli and provide a sustained release profile, longer retention time, and higher nasal absorption. The gelation mechanism depends on the polymer type. Generally, three types of polymers are used in these gels: thermo-, ionic and pH-sensitive polymers. These polymers facilitate the sol-to-gel transition based on changes in physiological conditions.
Concluding remarks
The correct use of antibiotics is crucial to minimize the risk of resistance. This could be achieved through innovations in drug formulation and delivery. Therefore, nasal administration is beneficial in the treatment of local, systemic and brain infections. Together with the use of QbD concepts and in situ gels, intranasal drug delivery could increase the effectiveness and retention time of antibiotics, thereby reducing the risk of antibiotic resistance.
Reference:
- Mardikasari SA, Sipos B, Csóka I, Katona G. Nasaler Weg zur Antibiotikaabgabe: Fortschritte, Herausforderungen und zukünftige Chancen bei der Anwendung der Quality-by-Design-Konzepte. Journal of Drug Delivery Science and Technology, 2022, DOI: https://doi.org/10.1016/j.jddst.2022.103887, https://www.sciencedirect.com/science/article/pii/S1773224722007985
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