Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

Abstract

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies.

Study the Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles

“…Its mucoadhesive properties is attributed to the interaction of the carbopol poly(acrylic acid) with the mucin by a combination of hydrogen bonding and electrostatic interaction [ 54 ]. Carbopol-based in situ gel demonstrated improving ophthalmic brinzolamide bioavailability and showed an extended drug release over a period of 8 h [ 55 ]. A good correlation between carbopol biodegradability and drug release has been previously mentioned.…”

Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self‐Healing Supramolecular Gel

“…Direct transport of molecules from the nasal cavity to the brain can occur along the olfactory and/or trigeminal nerves, originating in the CB and pons of the BS, respectively. [ 15b ] For instance, olfactory transfer for [ 3 H]dopamine has been reported and [ 125 I]insulin‐like growth factor‐I undergoes both olfactory and trigeminal pathways to reach brain and spinal cord following nasal administration. [ 32 ] The current data suggest a combination of both pathways accounts for the transport of [ 3 H] l‐ DOPA hydrogel after nasal delivery and that the trigeminal route may dominate the transport.…”

“…[ 14 ] We reasoned that supramolecular gels could be ideally suited to this application, given their potential for self‐healing and self‐assembly in situ, combined with their soft rheological properties. Although there has been rising interest in the use of responsive polymer gels for nasal drug delivery, [ 15 ] perhaps surprisingly, in spite of the attention focused on low‐molecular‐weight gelators, [ 3 ] they have not previously been explored in this regard. There have been isolated reports in which l‐ DOPA has been incorporated in different ways into supramolecular gels, [ 16 ] but these have not been applied in a pharmaceutical setting.…”

Ophthalmic In Situ Gels with Balsam Poplar Buds Extract: Formulation, Rheological Characterization, and Quality Evaluation

“…In situ gels, due to their viscosity, slow down the speed of drug elimination from the eye [ 46 ]. An important step in the formulation of in situ gels is the choice of excipients, which could ensure the stability of preparations without changing the activity of bioactive ingredients, and be non-irritant—especially when used locally on the surface of the eye [ 61 , 62 ]. Poloxamer 407, chosen for the production of gels, is often used for ophthalmic preparations as a substance resistant to temperature changes [ 63 , 64 ].…”