Design and optimization of chitosan-coated solid lipid nanoparticles containing insulin for improved intestinal permeability using piperine.

The objective of this research was to optimize the composition and performance of chitosan-coated solid lipid nanoparticles carrying insulin (Ch-In-SLNs) and to assess the potential of piperine in enhancing the intestinal permeability of insulin from these SLNs in vitro. The SLNs were formulated from glyceryl behenate (GB), soya lecithin, and poloxamer® 407, and then coated with a combination of chitosan and piperine to facilitate insulin penetration across the gastrointestinal (GI) mucosa. A Box-Behnken Design (BBD) was utilized to optimize the Ch-In-SLNs formulations, with PDI, particle size, zeta potential, and association efficiency (AE) serving as the response variables. The resulting Ch-In-SLNs exhibited excellent monodispersity (PDI = 0.4), optimal particle size (654.43 nm), positive zeta potential (+36.87 mV), and low AE values. The Ch-In-SLNs demonstrated sustained release of insulin for 12 h in simulated gastric fluid (SGF) and intestinal fluid (SIF), with increased release in the latter. After incubation in SGF and SIF for 12 h, the insulin SLNs retained 54 and 41 % of their initial insulin load, respectively, indicating effective protection from gastric enzymes. Permeation studies using goat intestine and Caco-2 cell lines indicated improved insulin permeation in the presence of piperine. Additionally, cell uptake studies confirmed the role of piperine in enhancing insulin permeation.

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

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.