Ionic Liquid Transdermal Patches of Two Active Ingredients Based on Semi-Ionic Hydrogen Bonding for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

Design and Evaluation of a Dual-Sensitive In Situ Gel for the Controlled Release of Pranoprofen.

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1ß, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

ROS/pH dual-sensitive emodin-chlorambucil co-loaded micelles enhance anti-tumor effect through combining oxidative damage and chemotherapy.

The high level of reactive oxygen species (ROS) at the tumor site has been widely used in the tumor targeted delivery. However, the ROS stimulus-responsive vector itself is also a ROS consumer, and the consumption of endogenous ROS may not be sufficient to maintain sustained drug release. In this study, we designed and synthesized ROS/pH dual-sensitive polymer micelles for the co-delivery of emodin (EMD) and chlorambucil (CLB). The release of quinone methides (QM) can consume glutathione (GSH), on the one hand, it can enhance the chemotoxicity of phenylbutyrate nitrogen mustard, on the other hand, emodin can induce oxidative damage of tumor cells and maintain the sustained targeted release of drugs.