In a recent study published in Journal of Drug Delivery Science and Technologyresearchers reviewed advances and challenges in intranasal antibiotic delivery.
Antibiotics are substances that act against bacteria to prevent or treat infectious diseases. The overuse of antibiotics is particularly contributing to increasing bacterial resistance. As a result, oral administration of antibiotics was prevalent and preferred. However, oral administration may have adverse effects on systemic distribution. Therefore, the way antibiotics are administered is crucial to increase bioavailability and minimize unwanted adverse outcomes and the risk of resistance.
Nasal administration of antibiotics could be paramount for upper respiratory tract infections. Intranasal administration is noninvasive and offers several advantages, such as rapid onset of action, ease of administration, and local and systemic availability. In this review, researchers discussed different approaches for intranasal antibiotic delivery.
Review Article – The Nasal Route of Antibiotic Delivery: Advances, Challenges and Future Opportunities Using Quality by Design Concepts. Image credit: Josep Suria / Shutterstock
Mechanism of nasal drug delivery
The nasal cavity is primarily used to treat upper respiratory conditions such as nasal/lung infections, sinusitis, allergic rhinitis and congestion. The meatus is the best area for local treatment because it is connected to the sinus openings. Any topically acting drug requires a longer residence time and smaller doses could be used for direct administration at the site of action.
The respiratory tract is the largest area of the nasal passages with vascularized mucosa and is crucial for the systemic absorption of drugs. In addition, 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 such, it could moderate the systemic side effects of central nervous system (CNS) agents. Other possible mechanisms of drug entry into the brain include the olfactory and trigeminal nerve pathways. Intranasal administration could circumvent two critical problems in drug delivery to the brain—hepatic metabolism and the BBB.
Limitation of nasal administration
Nasal mucociliary clearance limits the residence time of the drug in the nasal cavity and reduces the permeability of the drug through the nasal mucosa. In addition, enzymatic degradation and transport proteins are significant barriers to drug bioavailability. Efflux systems and transporters are crucial for drug absorption and distribution into the CNS and systemic circulation. In addition, several enzymes in the nasal passages affect drug metabolism.
Nasally administered antibiotics
Several antibiotics have been tested for nasal administration. These include, but are not limited to, 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 effectively reduced the number Staphylococcus aureus in the maxillary sinus. Similarly, vancomycin nasal irrigation is used for sinonasal polyps. In addition, intranasal delivery devices have been developed to improve clinical outcomes.
Optimization of intranasal administration of antibiotics
Quality by design (QbD) is a knowledge and risk-based quality management tool in pharmaceutical development. The QbD methodology includes examination of Quality Target Product Profiles (QTPP), identification of critical quality attributes (CQA) of products and risk assessment (RA).
Application of these QbD concepts may offer logical ways to design the best formulation strategies in early development to optimize antibiotic delivery after nasal administration. QTPP parameters for intranasal antibiotics are mainly related to the ability of the product to stay in the nasal cavity, avoid mucociliary clearance and release the drug (distribution profile).
CQAs are physical, biological, microbiological or chemical properties that affect the quality of the final product. For example, CQA parameters for intranasal antibiotics affect adhesion, stability, distribution, dissolution, permeability, and solubility. Among the various innovative approaches developed for intranasal antibiotic delivery, vizn there gels are the most promising.
On the page gels exhibit a sol-to-gel transition in response to external stimuli and offer a sustained release profile, extended retention time and higher nasal absorption. The gelation mechanism depends on the type of polymer and 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.
Correct use of antibiotics is vital to minimize the risk of resistance. This could be achieved through innovations in drug formulations and administration. As such, the nasal route of administration is advantageous in the treatment of local, systemic and cerebral infections. Together with the application of QbD concepts and on the page gels, intranasal drug delivery could increase the efficacy and retention time of antibiotics, thereby reducing the risk of antibiotic resistance.
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