Thermosensitive In Situ Gels for Joint Disorders: Pharmaceutical Considerations in Intra-Articular Delivery

Abstract

The intra-articular administration of conventional drug solutions or dispersions in joint diseases such as osteoarthritis has a relatively short retention time and, therefore, limited therapeutic effect. Thermosensitive polymer solutions that exhibit a sol–gel phase transition near body temperature after injection can prolong drug retention by providing a depot from which the drug release is sustained while relieving inflammation and preventing degradation of the joint complex. Thermosensitive hydrogels have in recent times garnered considerable attention in the intra-articular therapeutics of joint diseases such as osteoarthritis. Among the stimuli-responsive gelling systems, most research has focused on thermosensitive hydrogels. These gels are preferred over other stimuli-sensitive hydrogels since they have well-controlled in situ gelling properties and are also easier to load with drugs. Temperature-sensitive polymers, such as block copolymers or poloxamers, are frequently used to modify their gelation properties, usually in combination with other polymers. They are compatible with most drugs but may pose formulation challenges in terms of their low-response time, highly fragile nature, and low biocompatibility. The stability and biodegradability of implant hydrogels can control the drug release rate and treatment efficacy. This review stresses the application of thermosensitive gels in joint disorders and summarizes recent developments for intra-articular application, including the incorporation of nanoparticles. The hydrogel composition, drug release mechanisms, and the challenges involved in their formulation and storage are also discussed.

Intra‐Articular Injection of Nanomaterials for the Treatment of Osteoarthritis: From Lubrication Function Restoration to Cell and Gene Therapy

“…[194,195] Thermal-responsive nanomaterials leverage the slight variations in temperature associated with pathological conditions to transition from liquid to gel states, forming a localized depot for sustained drug release. [196,197] Similarly, protease-responsive nanomaterials are also developed to release their therapeutic payloads in response to the activity of specific enzymes, such as metalloproteinases, which are upregulated in OA-affected joint. [198,199] These smart response mechanisms ensure that the drug release is not only precisely targeted but also temporally controlled, aligning drug availability with the pathological state of the joint.…”

Investigating the rheological behavior of Poloxamer-chitosan thermogel for in situ drug delivery of doxorubicin in breast cancer treatment: designed by response surface method (RSM)

“…Thermogels undergo sol-gel transition under certain temperature conditions and the temperature of the gel shows the temperature of the phenomenon. Therefore, the basic requirement to create a viscous preparation is to determine the solgel transition temperature [27]. Chitosan is a hydrolyzed polysaccharide derivative of chitin and a widespread biopolymer in nature, which is non-toxic, biocompatible and biodegradable [28].…”