In situ gel-forming system: an attractive alternative for nasal drug delivery.

Intranasal delivery is one of the most interesting and challenging endeavors facing pharmaceutical scientists. The conventional nasal drug delivery systems including solutions, suspensions, and ointments show drawbacks such as short residence in the nasal cavity, highly variable efficiency, low permeability, and inconvenient administration. In situ gel-forming systems are an interesting polymeric system that exists as flowing aqueous solution before administration and undergoes phase transition to form a viscoelastic gel in a physiologic environment. Benefiting from the merits of both a solution and a gel, an impressive number of in situ gel-forming systems induced by temperature, pH, and ions have been prepared for use in nasal drug delivery in the past few years. In situ gel-forming systems increase the retention of drugs in the nasal cavity, and some of them also show permeation-enhancing capabilities. This article reviews the in situ gel-forming systems used for nasal drug delivery and introduces their gelling mechanisms and other favorable features for intranasal delivery. It also describes the release patterns and drug stability of in situ gels as well as their in vivo performances and local safety following nasal administration.