In situ gelling and mucoadhesive polymers: why do they need each other?

ABSTRACT

Introduction: Mucosal drug delivery is an attractive route of administration, particularly in overcoming deficits of conventional dosage forms including high first-pass metabolism and poor bioavailability. Fast drainage from the target mucosa, however, represents a major limitation as it prevents sufficient drug absorption. In order to address these problems, mucoadhesive in situ gelling drug delivery systems have been investigated as they facilitate easy application in combination with a longer residence time at the administration site resulting in more desirable therapeutic effects.

Areas covered: The present review evaluates the importance of the combination of mucoadhesive and in situ gelling polymers along with mechanisms of in situ gelation and mucoadhesion. In addition, an overview about recent applications in mucosal drug delivery is provided.

Expert opinion: In situ gelling and mucoadhesive polymers proved to be essential excipients in order to prolong the mucosal residence time of drug delivery systems. Due to this prolonged residence time both local and systemic therapeutic efficacy of numerous drugs can be substantially improved. Depending on the site of administration and the incorporated drug, combinations of different polymers with in situ gelling and mucoadhesive properties are needed to keep the delivery system as long as feasible at the target site.

KEYWORDS:

• Hydrogel
• in situ gelation
• mucoadhesion
• mucoadhesive polymers
• mucosal drug delivery
• sol to gel

Article highlights

• In situ gelling systems for mucosal drug delivery appear to be an effective noninvasive approach to bypass the first-pass effect and improve the bioavailability of therapeutics.

• Shortcomings as short residence time of drug due to mucociliary clearance or fast leakage from the site of application can be minimized by increased viscosity and improved mucoadhesive properties.

• A major advantage is the feasibility to store and administer the formulation as a sol, which then transforms to a gel at physiological conditions preventing fast clearance or drainage, hence increasing the residence time.

• Phase transition from sol to gel can be triggered by multiple factors, such as increased temperature, changes in pH, presence of specific ions or oxidative conditions.

• Mucoadhesive polymers like poly(acrylic acid), gellan gum, hyaluronic acid, chitosan, cellulose derivates, and thiolated polymers, so-called thiomers, have been widely explored for mucosal drug delivery.

• Various research reports suggest that mucoadhesive in situ gels can pave way for improved local treatment, controlled systemic therapeutic effects, targeted delivery to the central nervous system, and delivery of vaccines or plasmid DNA.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.