Dual-jet electrospun PDLGA/PCU nonwovens as promising mesh implant materials with controlled release of sirolimus and diclofenac.

Dual-jet electrospinning was employed to produce two-component, partially degradable drug releasing nonwovens with interlacing of poly(D,L-lactide-co-glycolide) (PDLGA) and different poly(carbonate urethanes) (PCUs). Diclofenac sodium and sirolimus were released simultaneously from the copolyester carrier. The research focused on determining of release profiles of drugs, depending on the hydrophilicity of introduced PCU nanofibers. The influence of drugs incorporation on the hydrolytic degradation of the PDLGA and mechanical properties of nonwovens was also studied. Evaluation for interaction with cells in vitro was investigated on a fibroblast cell line in cytotoxicity and surface adhesion tests. Significant changes in drugs release rate, depending on the applied PCU were observed. It was also noticed, that hydrophilicity of drugs significantly influenced the hydrolytic degradation mechanism and surface erosion of the PDLGA, as well as the tensile strength of nonwovens. Tests carried out on cells in an in vitro experiment showed that introduction of sirolimus caused a slight reduction in the viability of fibroblasts as well as a strong limitation in their capability to colonize the surface of fibers. Due to improvement of mechanical strength and the ability to controlled drugs release, the obtained material may be considered as prospect surgical mesh implant in the treatment of hernia.

Preventive effect of rebamipide on NSAID-induced lower gastrointestinal tract injury using FAERS and JADER.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their antipyretic, analgesic, and anti-inflammatory properties. However, various aspects of NSAID-induced lower gastrointestinal tract injury remain unclear, and effective prophylaxis has not been established. Based on its pharmacological effect and clinical trials, rebamipide may prevent lower gastrointestinal tract injury, although this evidence is limited by the small scale of trials. The present study used the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Event Reporting Database (JADER) to assess the efficacy of rebamipide in combination with loxoprofen and diclofenac in preventing NSAID-induced lower gastrointestinal tract injury. The calculated reporting odds ratio and 95% confidence interval (CI) for rebamipide in combination with loxoprofen and diclofenac were 1.15 (95% CI 0.88-1.51) and 1.28 (95% CI 0.82-2.01) for FAERS, and 0.50 (95% CI 0.35-0.71) and 0.43 (95% CI 0.27-0.67) for JADER, respectively. No signal was detected when combining drugs. These results suggest a prophylactic effect of rebamipide on NSAID-induced lower gastrointestinal tract injury.

Microchannel-embedded implantable device with fibrosis suppression for prolonged controlled drug delivery.

For the prolonged, controlled delivery of systemic drugs, we propose an implantable drug-delivery chip (DDC) embedded with pairs of a microchannel and drug-reservoir serving as a drug diffusion barrier and depot, respectively. We pursued a DDC for dual drugs: a main-purpose drug, diclofenac (DF), for systemic exposure, and an antifibrotic drug, tranilast (TR), for local delivery. Thus, the problematic fibrotic tissue formation around the implanted device could be diminished, thereby less hindrance in systemic exposure of DF released from the DDC. First, we separately prepared DDCs for DF or TR delivery, and sought to find a proper microchannel length for a rapid onset and sustained pattern of drug release, as well as the required drug dose. Then, two distinct DDCs for DF and TR delivery, respectively, were assembled to produce a Dual_DDC for the concurrent delivery of DF and TR. When the Dual_DDC was implanted in living rats, the DF concentration in blood plasma did not drop significantly in the later periods after implantation relative to that in the early periods before fibrotic tissue formation. When the Dual_DDC was implanted without TR, there was a significant decrease in the blood plasma DF concentration as the time elapsed after implantation. Biopsied tissues around the Dual_DDC exhibited a significant decrease in the fibrotic capsule thickness and collagen density relative to the Dual_DDC without TR, owing to the effect of the local, sustained release of the TR.

SZAP exerts analgesic effects on rheumatalgia in CIA rats by suppressing pain hyperalgesia and inhibiting TRPV1 and P2X3.

ETHNOPHARMACOLOGICAL RELEVANCE: ShexiangZhuifeng Analgesic Plaster (SZAP) is a traditional Chinese medicine and transdermal formulation composed of many Chinese herbs and active compounds. SZAP was recently approved by the China Food and Drug Administration for the treatment of pain associated with osteoarticular diseases and is preferred by most rheumatoid arthritis patients in China. However, its mechanism has not been elucidated in detail. AIM OF THE STUDY: We sought to determine the analgesic effect of SZAP in collagen-induced arthritis (CIA) rats and explore the underlying mechanisms of pain transmission, such as via the TRPV1 and P2X3 receptors. METHODS: After CIA was established, rats were treated with SZAP for 7 days. Paw thickness, arthritis score, and haematoxylin and eosin staining were used to evaluate the effectiveness of SZAP. Paw withdrawal threshold (PWT) and tail-flick latency (TFL) were used to estimate the analgesic effect of SZAP. The levels of PGE2, BK, 5-HT, SP, and CGRP in the serum and synovium were determined using ELISA kits, and ATP in the synovium was measured using HPLC. The expression of TRPV1 and P2X3 in the DRG was detected using western blotting and immunofluorescence. TRPV1 and P2X3 agonists were further used to determine the analgesic effects of SZAP on CIA rats based on PWT and TFL. RESULTS: SZAP not only significantly ameliorated arthritis scores and paw thickness by improving the pathological damage of synovial joints, but also remarkably alleviated pain in CIA rats. Further, treatment with SZAP significantly reduced peripheral 5-HT, PGE2 BK, SP, CGRP, and ATP. Additionally, the expression of TRPV1 and P2X3 in the DRG was markedly downregulated by SZAP. Interestingly, the analgesic effect of SZAP was weakened (reduction of PWT and TFL) when TRPV1 and P2X3 were activated by capsaicin or α,ß-meATP, respectively. CONCLUSION: SZAP ameliorates rheumatalgia by suppressing hyperalgesia and pain transmission through the inhibition of TRPV1 and P2X3 in the DRG of CIA rats.

Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-ß1.

A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it is essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase hypoxia-inducible factor 1-alpha (HIF-1α) and transforming growth factor beta 1 (TGF-ß1) proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-ß receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-ß1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.

Experimental evidence for proarrhythmic effects of nonsteroidal anti-inflammatory drugs in a sensitive whole-heart model.

BACKGROUND: Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS: Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 µM), indomethacin (Group 2, n = 13; 10 and 20 µM) and diclofenac (Group 3, n = 13; 10 and 20 µM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION: The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

Efficacy of ultramicronised diclofenac in patients with osteoarthritis - systematic review with network meta-analysis.

OBJECTIVE: This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis. PATIENTS AND METHODS: Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome. RESULTS: Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%). CONCLUSIONS: Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.

Estudio comparativo de una asociación de diclofenac, betametasona y vitamina b12 (blokium b12®) con diclofenac (sin asociar) en el tratamiento de patología dolorosa de columna con compromiso neural / COMPARATIVE STUDY OF AN ASSOCIATION OF DICLOFENAC, BETAMETASONE AND VITAMIN B12 (BLOKIUM B12®) WITH DICLOFENAC (WITHOUT ASSOCIATION) IN THE TREATMENT OF PAINFUL SPINE PATHOLOGY WITH NEURAL COMMITMENT

El dolor lumbar bajo y el dolor cervical con o sin irradiación son causas muy comunes de consulta a los médicos generalistas en los países desarrollados. La discopatía aguda y el dolor por estenosis del canal espinal son los diagnósticos más frecuentes. La postura tradicional ha sido la de administrar antiinflamatorios no esteroideos (AINES) para estas lumbalgias o cervicalgias agudas. Cuando existe irradiación neural por compresión radicular es usual asociar al AINE un corticoide a baja dosis, así como un antineurítico, para lograr un mejor resultado. Con el objeto de documentar la utilidad de esta práctica habitual, efectuamos en 142 pacientes ambulatorios un estudio multicéntrico randomizado que compara la efectividad y la tolerancia de una asociación a dosis fija de diclofenac, betametasona y cianocobalamina administrada por vía oral versus la administración de diclofenac como monofármaco en el tratamiento de la patología dolorosa de la columna lumbar y cervical asociada a compresión neural. La asociación demostró ser más eficaz en controlar el dolor y mejorar la funcionalidad de los pacientes que la administración de diclofenac en forma aislada y se asoció a escasos efectos colaterales, principalmente digestivos

Low back pain and neck pain with or without radiation are very common causes of consultation with general practitioners in developed countries. Acute discopathy and pain due to spinal canal stenosis are the most frequent diagnoses. The traditional approach has been to administer non-steroidal antiinflammatory drugs (NSAIDs) for these acute low back or cervical pain. When there is neural radiation due to root compression, it is usual to associate a low-dose corticosteroid with the NSAID, as well as an antineuritic, to achieve a better result. In order to document the usefulness of this routine practice, we conducted a randomized multicenter study in 142 outpatients that compared the effectiveness and tolerance of a fixed-dose combination of diclofenac, betamethasone, and cyanocobalamin administered orally versus the administration of diclofenac as Monopharmaceutical in the treatment of painful pathology of the lumbar and cervical spine associated with neural compression. The association proved to be more effective in controlling pain and improving the functionality of patients than the administration of diclofenac in isolation and was associated with few side effects, mainly digestive

Rectally Administered Low-Dose Diclofenac Has No Effect on Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Propensity Score Analysis.

OBJECTIVES: We evaluated the preventive effect of low-dose diclofenac (25-50 mg) on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by propensity score matching analysis. METHODS: We retrospectively analyzed the data of 515 patients who underwent ERCP for the first time with or without the rectal administration of low-dose diclofenac before the procedure. For the purpose of minimization of the intrinsic selection bias, we compared the incidence rate of PEP between the diclofenac and control group after propensity score matching. RESULTS: Post-ERCP pancreatitis developed in 15 patients (2.9%). There was no significant difference in the incidence of PEP between the diclofenac (2.4%) and control group (3.3%) (P = 0.608). One hundred ninety matched pairs were generated by propensity score matching and analyzed; however, the incidence rate of PEP was the same in both groups (2.1%, P = 1.000). In the subgroup analysis using data of patients with high-risk factors for developing PEP, the incidence rate of PEP was comparable between the diclofenac (3.8%) and control groups (4.0%) (P = 0.917). CONCLUSIONS: In our propensity score analysis, rectal administration of low-dose diclofenac was not shown to be useful in preventing PEP.

Cefepime and diclofenac sodium combined treatment-potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism.

Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.

Is the Combination of Rectal Diclofenac and Intravenous Ringer Lactate Superior to Individual Therapy for Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective, Open-Label, Single-Center Randomized Trial.

METHODS: This was single-center, open-label, randomized trial. Patients who were undergoing ERCP and who were at high risk for the development of PEP were selected for the study. Patients were randomized into 3 treatment groups: diclofenac suppository group, RL group, and a combination group. RESULTS: Eight of 57 patients (14.03%) in the diclofenac group, 9 of 57 patients (15.78%) in the RL group, and 6 of 57 patients (10.52%) in the combination group developed PEP. The incidence of PEP between the three groups was not statistically significant (P = 0.70). Serum amylase level of >252 U/L had 91.3% sensitivity and 92.6% specificity for the diagnosis of PEP. CONCLUSIONS: Post-ERCP pancreatitis is usually mild to moderate 95% times. Female sex, age younger than 50 years, a benign indication of ERCP, and low bilirubin levels have higher chances of PEP. A combination of rectal diclofenac and hydration with RL does not offer better protection for PEP, as compared with individual prophylaxis.

Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage.

OBJECTIVE AND DESIGN: Montelukast, a cysteinyl leukotriene receptor antagonist, exhibits antiinflammatory action. We tested whether exposure to montelukast plus nonsteroidal antiinflammatory drugs (NSAIDs) elicits better control of paw inflammation in the rat formalin test and improves associated gastric damage. MATERIALS: A total of 46 adult male rats were used in the study. TREATMENTS: We evaluated separate and combined effects of montelukast (20 mg/kg), celecoxib (COX2 inhibitor, 10 mg/kg), and diclofenac (nonselective COX1/COX2 inhibitor, 10 mg/kg) on paw and gastric damage in the rat formalin test. RESULTS: Individual pretreatments of rats with montelukast, diclofenac, or celecoxib partly reduced formalin-induced increases in (i) paw edema, fibrosis, and inflammatory cells, (iii) serum interleukin-6 (IL-6) and leukotrienes (LTB4 and LTD4), and (iv) paw expressions of inducible nitric oxide synthase (iNOS) and COX2. These effects were accentuated in rats treated with montelukast plus diclofenac or montelukast plus celecoxib. Alternatively, montelukast or celecoxib, but not diclofenac, alleviated formalin-evoked gastric damage and increments in tumor necrosis factor-α and decrements in prostaglandin-E2. These advantageous gastric influences were potentiated in rats treated with montelukast plus celecoxib. CONCLUSIONS: While montelukast equally enhances antiinflammatory action of diclofenac or celecoxib via downregulating iNOS/COX2/LTs/IL-6 signaling, its gastroprotective action is preferentially potentiated by celecoxib.

A 25 mg rectal dose of diclofenac for prevention of post-ERCP pancreatitis in elderly patients.

OBJECTIVES: A 50-100 mg rectal dose of diclofenac or indomethacin is recommended for prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP); however, limited data are available regarding the appropriate dose to prevent PEP in elderly patients. We aimed to evaluate the efficacy and safety of 25 mg diclofenac in preventing PEP in elderly patients. Material and methods: Overall, 276 patients with naive papilla, aged over 75 years, were included in the present study between April 2013 and March 2020. We retrospectively evaluated the risk of PEP in patients over 75 years, administered with or without 25 mg diclofenac 30 min before ERCP using inverse probability of treatment weighting (IPTW) analysis. Results: Patients were categorized into the diclofenac group (83 patients) or non-diclofenac group (193 patients). The incidence rate of PEP in the diclofenac group was significantly lower than that in the non-diclofenac group (4% vs. 14%, p = .01). Multivariate analysis revealed that 25 mg diclofenac was an independent protective factor against PEP in elderly patients aged over 75 years (odds ratio [OR] = 0.17; 95% confidence interval [CI] = 0.04-0.67; p = 0.01). This protective effect of diclofenac against PEP remained robust after IPTW analysis (OR = 0.11; 95% CI = 0.03-0.40; p = .001). No adverse events related to diclofenac were observed. Conclusion: Diclofenac (25 mg) was considered effective and safe for preventing PEP in elderly patients. Our results may provide a new strategy for preventing PEP in elderly patients.

iTRAQ-based quantitative proteomic analysis reveals the toxic mechanism of diclofenac sodium on the kidney of broiler chicken.

Diclofenac sodium (DS) is one of the nonsteroidal anti-inflammatory drugs (NSAIDs), which exhibits potent toxicity to birds. To search the molecular mechanism of DS induced nephrotoxicity in broiler chicken, 20 apparently healthy 30-day old broiler chickens were separated randomly into two groups (n = 10): Group A was kept as control while DS was administered at the dose rate of 10 mg/kg body weight in group B through oral gavage. Kidney samples were collected, and the proteins were identified and quantified by iTRAQ. 434 differentially expressed proteins (DEPs) were screened, including 277 up-regulated DEPs and 157 down-regulated DEPs. The functional annotation and classification results indicated that DEPs were significantly enriched in apoptosis and metabolism-related pathways via GO and KEGG analysis. Compared with the control group, the most significant enrichment pathways are "ribosome", "metabolic pathways" and "protein processing in endoplasmic reticulum". Based on the proteomic results and relevant literature, some DEPs that potentially related to the toxicity of DS were screened. The mRNA transcript levels of these DEPs were characterized by qRT-PCR, and the results showed that Slc22a7, Gatm, Glud1, Agxt2 and Gldc were significantly down-regulated, while Gsl, Gpt2 and Asns were significantly up-regulated. We speculate that the toxic mechanism of DS to chicken might be that it induces kidney cell apoptosis, interferes with purine metabolism and inhibits the expression of OAT2. The current study provides a reference for elucidating the nephrotoxic mechanism of diclofenac sodium to broiler chicken from the molecular perspective.

Quercetin decreases the antinociceptive effect of diclofenac in an arthritic gout-pain model in rats.

OBJECTIVE: To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain. METHODS: The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination. KEY FINDINGS: DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P < 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P < 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P < 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively). CONCLUSIONS: All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Layered terbium hydroxides for simultaneous drug delivery and imaging.

Layered rare-earth hydroxides have begun to gather increasing attention as potential theranostic platforms owing to their extensive intercalation chemistry combined with magnetic and fluorescent properties. In this work, the potential of layered terbium hydroxide (LTbH) as a platform for simultaneous drug delivery and fluorescence imaging was evaluated. LTbH-Cl ([Tb2(OH)5]Cl·yH2O) was loaded with three nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen, and naproxen) via ion-exchange. Drug release studies in phosphate buffered saline (pH = 7.4) revealed all three formulations release their drug cargo rapidly over the course of approximately 5 hours. In addition, solid state fluorescence studies indicated that fluorescence intensity is strongly dependent on the identity of the guest anion. It was postulated that this feature may be used to track the extent of drug release from the formulation, which was subsequently successfully demonstrated for the ibuprofen loaded LTbH. Overall, LTbH exhibits good biocompatibility, high drug loading, and a strong, guest-dependent fluorescence signal, all of which are desirable qualities for theranostic applications.