Phytoconstituents-Based Nanotherapeutic Approach for the Effective Management of Joint Inflammatory Condition: Arthritis.

Arthritis, a prevalent inflammatory joint condition, presents challenges for effective therapeutic interventions, with conventional treatments often limited in efficacy and associated with adverse effects. Recent years have witnessed a growing interest in exploring natural compounds, particularly phytoconstituents, renowned for their anti-inflammatory and joint-protective properties. This review aims to illuminate the potential of employing nanotherapeutic approaches with phytoconstituents for enhanced arthritis management. The integration of nanotechnology with phytoconstituents emerges as a promising strategy, addressing limitations in traditional arthritis treatments. Nanocarriers like liposomes and nanoparticles provide a platform for targeted drug delivery, improving the bioavailability of phytoconstituents. Furthermore, the combined effects of phytoconstituents can be leveraged to target multiple pathways in arthritis pathogenesis, including inflammation, oxidative stress, and cartilage degradation. Key phytoconstituents, such as curcumin, resveratrol, and quercetin, exhibit anti-inflammatory and immunomodulatory properties. Nevertheless, their therapeutic potential is often impeded by challenges like poor solubility, stability, and bioavailability. Nanocarriers offer solutions by enhancing pharmacokinetics and enabling sustained release, thereby boosting overall therapeutic efficacy. The review explores the mechanisms underlying the anti-arthritic effects of phytoconstituents and their nanoformulations, including the modulation of pro-inflammatory cytokines, inhibition of matrix metalloproteinases, and reduction of oxidative stress. In summary, the integration of phytoconstituents with nanotechnology presents a promising avenue for developing targeted and effective arthritis therapies. This comprehensive review serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking innovative approaches to address the intricate challenges associated with arthritis management.

Rubia cordifolia L. Attenuates Diabetic Neuropathy by Inhibiting Apoptosis and Oxidative Stress in Rats.

BACKGROUND: Diabetic neuropathy is a debilitating manifestation of long-term diabetes mellitus. The present study explored the effects of the roots of Rubia cordifolia L. (R. cordifolia L.) in the Wistar rat model for diabetic neuropathy and possible neuroprotective, antidiabetic, and analgesic mechanisms underlying this effect. MATERIALS AND METHODS: Rats were divided into five experimental groups. An amount of 0.25% carboxy methyl cellulose (CMC) in saline and streptozotocin (STZ) (60 mg/kg) was given to group 1 and group 2, respectively. Group 3 was treated with STZ and glibenclamide simultaneously while groups 4 and 5 were simultaneously treated with STZ and hydroalcoholic extract of the root of R. cordifolia, respectively. Hot plate and cold allodynias were used to evaluate the pain threshold. The antioxidant effects of R. cordifolia were assessed by measuring Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). At the end of the study, sciatic nerve and brain tissues were collected for histopathological study. Bcl-2 proteins, cleaved caspase-3, and Bax were assessed through the Western blot method. RESULTS: R. cordifolia significantly attenuated paw withdrawal and tail flick latency in diabetic neuropathic rats. R. cordifolia significantly (p < 0.01) improved the levels of oxidative stress. It was found to decrease blood glucose levels and to increase animal weight in R. cordifolia-treated groups. Treatment with R. cordifolia suppressed the cleaved caspase-3 and reduced the Bax:Bcl2 ratio in sciatic nerve and brain tissue compared to the diabetic group. Histopathological analysis also revealed a marked improvement in architecture and loss of axons in brain and sciatic nerve tissues at a higher dose of R. cordifolia (400 mg/kg). CONCLUSION: R. cordifolia attenuated diabetic neuropathy through its antidiabetic and analgesic properties by ameliorating apoptosis and oxidative stress.

Thiazole derivative based topical nanoemulgel for inhibition of bacterial virulence in surface infections.

Objectives: Antimicrobial resistance emerged as a global challenge owing to limited therapeutic options to control infections. Pseudomonas aeruginosa, an MDR pathogen already developed resistance against many conventional antibiotics. An "anti-virulence strategy" that targets bacterial virulence rather than growth proves effective against drug-resistant pathogens. Materials and Methods: Here, we used a structure-based drug design approach to identify lead molecules using the LasR receptor protein of P. aeruginosa as a target responsible for virulence production in this bacterium. From the identified hits, we developed lead-based nanoformulation and investigated its effectiveness for treating the P. aeruginosa associated surface-infection in-vivo. First, TC-based nanoemulsions were fabricated by high-pressure homogenization and evaluated for various in vitro parameters. The optimized nanoemulsions were thereby utilized to prepare NEG. Results: The nanoemulsion (F3) exhibited low droplet size (51.04±1.88 nm), PDI (0.065±1.14), and negative zeta potential (-33.65±0.82 mV). In animals, topical application of NEG-3 demonstrated significant improvement on skin permeability (459±10.17 µg), drug influx (18.99±0.76 µg/cm2 hr), and repressed the CFU of P. aeruginosa induced-surface infection (P≤ 0.001). The histology of rat skin demonstrated a significant effect for groups treated with TC-based NEGs as compared with a negative control group, whereas no significant effect was seen on rat liver indicating low systemic exposure to the drug. Also, NEG3 showed no significant changes under different stability conditions after 3 months. Conclusion: TC-based NEGs open up the possibility of a more effective way to combat serious surface infections caused by P. aeruginosa.

Development of Topical Nanoemulgel Using Combined Therapy for Treating Psoriasis.

This study focuses on the development of topical formulation of methoxsalen using Babchi oil as formulation component that can be applied at body surfaces providing sustained delivery and enhanced penetration of methoxsalen leading to significant epidermal localization and better anti-psoriatic activity. The combination of psoralens, that is, methoxsalen (synthetic) and Babchi oil (natural) has been developed into nanoemulgel formulations. A total of four nanoemulsion formulations was developed using Babchi oil as oil phase and Tween 80 as surfactant by high-pressure homogenization method. The prepared nanoemulsions were characterized for entrapment efficiency, mean droplet size, and zeta potential. Based on characterization results, the optimized nanoemulsion formulation(s) were incorporated into the carbopol gel base to make a nanoemulgel. The prepared nanoemulgel formulations were analyzed for pH, drug content determination, spreadability, viscosity, ex vivo skin permeation, and in vivo studies. The nanoemulsions showed droplet size between 51.3 and 146.7 nm, entrapment efficiency of 92.76%-98.10%, and zeta potential of -28.1 to -54.89 mev. The nanoemulsions showed varied in vitro drug release. In ex vivo skin permeation, nanoemulgel (NG2) showed increased penetration and localized accumulation of methoxsalen across the skin compared with plain gel. Ex vivo results were substantiated by in vivo results showing significant amelioration of hyperproliferative skin symptoms. The promising results suggested that nanoemulgel system is a suitable carrier for the topical delivery of methoxsalen-Babchi oil.

Potential Assessment of Topical Felbinac-Loaded Cubosomal Gel in Soft Tissue Injury in Albino Rats.

Muscle strain is one of the most common injuries with high intermittence rate. Due to diverseness of strain injuries, different experimental animal models are employed to investigate such injuries with reproducible results. Cubosomes, an emerging nano drug delivery tool, are considered ideal carriers for the topical delivery of lipophilic drugs to treat local inflammations with reduced frequency of application for prolonged periods. This work describes the development of Felbinac-loaded cubosomal gel and investigated the treatment of inflammation and tissue injury in vivo. Sciatic Function Index (SFI) is a simple clinical method to observe hind limb recovery in rats after induced injuries. First, cubosomes were fabricated by high-pressure homogenization process and evaluated for in vitro parameters. The optimized cubosome formulation was chosen to develop cubosomal gel and evaluated for in vitro parameters and also investigated time to recovery of SFI after strain induction in tibialis anterior muscles in rats. The cubosome formulation (F4) exhibited low droplet size (51.04 ± 1.37 nm)and polydispersity index (0.085 ± 1.13), and negative zeta potential (-32.8 ± 0.67 mV). In rats, topical application of cubosomal gel formulation (CGF) exhibited significant improvement in skin permeation (402 ± 6.08 µg) and drug flux (15.71 ± 0.82 µg/cm2 h) compared to plain gel. Also, CGF demonstrated significant difference in SFI from first to seventh day. The histology of rat skin showed significant effect for groups treated with Felbinac-loaded CGF compared to a negative control group.

Growing emergence of drug-resistant Pseudomonas aeruginosa and attenuation of its virulence using quorum sensing inhibitors: A critical review.

A perilous increase in the number of bacterial infections has led to developing throngs of antibiotics for increasing the quality and expectancy of life. Pseudomonas aeruginosa is becoming resistant to all known conventional antimicrobial agents thereby posing a deadly threat to the human population. Nowadays, targeting virulence traits of infectious agents is an alternative approach to antimicrobials that is gaining much popularity to fight antimicrobial resistance. Quorum sensing (QS) involves interspecies communication via a chemical signaling pathway. Under this mechanism, cells work in a concerted manner, communicate with each other with the help of signaling molecules called auto-inducers (AI). The virulence of these strains is driven by genes, whose expression is regulated by AI, which in turn acts as transcriptional activators. Moreover, the problem of antibiotic-resistance in case of infections caused by P. aeruginosa becomes more alarming among immune-compromised patients, where the infectious agents easily take over the cellular machinery of the host while hidden in the QS mediated biofilms. Inhibition of the QS circuit of P. aeruginosa by targeting various signaling pathways such as LasR, RhlR, Pqs, and QScR transcriptional proteins will help in blocking downstream signal transducers which could result in reducing the bacterial virulence. The anti-virulence agent does not pose an immediate selective pressure on growing bacterium and thus reduces the pathogenicity without harming the target species. Here, we review exclusively, the growing emergence of multi-drug resistant (MDR) P. aeruginosa and the critical literature survey of QS inhibitors with their potential application of blocking P. aeruginosa infections.

Development and Characterization of Niosomal Gel System using Lallementia royaleana Benth. mucilage for the treatment of Rheumatoid Arthritis.

Niosomes structural framework comprises of non-ionic surfactant-based microscopic lamellar structures which carries the potential to sustain the effect of drug from its delivery system. In present work, the attempt was made to identify the effect of different ingredients such as effect of Tweens and natural mucilage of Lallemantia royaleana Benth. on the performance of developed niosomal gel formulations in order to prolong the duration of action of drug and to minimize its side effects of topical conventional drug administration. All Ibuprofen loaded niosomes formulationswere prepared by ether injection method; using cetosteryl alcohol with different variants of Tweens and Spans. Various evaluation parameters were performed to confirm niosome formation. Further, the niosomes were incorporated into gel system and evaluated for in-vitro permeability study (ex-vivo) on excised rat skin by membrane diffusion method and in-vivo study by carrageenan induced rat paw edema model. The best selected niosome formulation F9 gave no sedimentation, layer separation and unchanged particle shapes and thus selected for gel preparation using Lallemantia royaleana Benth. mucilage and carbopol in different ratios. Ex-vivo and in-vivo studies indicated high skin retention and penetration rates within the skin for tests niosomal gel formulations (G1 & G2). The present study suggested that developed topical gel formulation provides enhance permeability and longer duration of drug action over conventional gels.