Synthesis, physicochemical characterization, and investigation of anti-inflammatory activity of water-soluble PEGylated 1,2,4-Triazoles.

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and 1H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates. For SAR study, all PEGylated 1,2,4-triazoles 5-8 performed potential anti-inflammatory activity on LPS-induced RAW 264.7 cells (IC50 = 3.42-7.81 µM). Moreover, the western blot result showed PEGylated 1,2,4-triazole 7d performed 5.43 and 2.37 folds inhibitory activity over iNOS and COX-2 expressions. On the other hand, the cell viability study revealed PEGylated 1,2,4-triazoles 7 and 8 with PEG molecular weight more than 600 presented better cell safety (cell viability > 95 %). Through the solubility and in vitro plasma stability studies, PEGylated 1,2,4-triazoles 7a-d exhibited higher hydrophilicity and prolonged 2.01 folds of half-life in compound 7d. Furthermore, the in vivo anti-inflammatory and gastric safety results indicated PEGylated 1,2,4-triazole 7d more effectively decreased the inflammatory response in edema and COX-2 expression and exhibited higher gastric safety than Indomethacin. Following the in vitro and in vivo study results, PEGylated 1,2,4-triazole 7d possessed favorable solubility, plasma stability features, safety, and significant anti-inflammatory activity to become the potential water-soluble anti-inflammatory candidate.

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

Anti-solvent Precipitation Method Coupled Electrospinning Process to Produce Poorly Water-Soluble Drug-Loaded Orodispersible Films.

Orodispersible films (ODFs) are more convenient for paediatric and geriatric patients to take as compared to conventional tablets and capsules. Electrospinning has recently been attempted to produce ODFs. This study investigated the feasibility of formulating poorly water-soluble drug into ODFs using electrospinning technology coupled with the anti-solvent precipitation method. Piroxicam (PX), a poorly water-soluble drug, was chosen as a model drug. Polyvinyl alcohol and polyvinylpyrrolidone were used as film forming polymers. PX microcrystals were prepared using poloxamer as the stabilizer with the anti-solvent precipitation method, and then loaded in ODFs through the electrospinning process. The obtained ODFs were characterized using a scanning electron microscope, X-ray powder diffraction and Fourier transform infrared spectroscopy with respect to the morphology, solid state and potential molecular interaction between the model drug and polymers. The mechanical property, disintegration and dissolution rate of the obtained ODF were evaluated using dynamic mechanical analysis, a customized method and USP2 apparatus. The results showed that PX microcrystals suspended in polymeric solutions could be readily electrospun into fibrous films, where the microcrystals scattered between the fibers. The electrospun fibrous film-based ODFs exhibited satisfactory mechanical behaviour, and fast disintegration upon the polymer selection. In the dissolution tests, almost 90% of PX was dissolved within 6 min from the ODFs, whereas 40% of PX dissolved from physical mixtures in 60 min. This study demonstrated that poorly water-soluble drugs could be formulated into ODFs with satisfactory quality attributes by combining micronization and the electrospinning process.

Impacts of Polymeric Additives on Nucleation and Crystal Growth of Indomethacin from Supersaturated Solutions.

Three polymers, polyvinylpyrrolidone (PVP K30), hydroxypropyl methyl cellulose (HPMC E5), and Kollidone VA64 (PVP-VA64), have been assessed for their impact on the nucleation and crystal growth of indomethacin (IND) from supersaturation solutions. PVP was the most effective inhibitor on IND nucleation among three polymers, but the effect of three polymers on inhibiting nucleation is quite limited when the degree of supersaturation S is higher than about 9. Analysis of the nucleation data by classical nucleation theory model generally afforded good data fitting with the model and showed that addition of polymers may affect the crystal/solution interfacial free energy γ and also the pre-exponential kinetic factor. PVP-VA showed better inhibitory effects on crystal growth of IND when the polymer concentration is high (0.1%, w/w) as reflected by the crystal growth inhibition factor R, and PVP exhibited relatively stronger effects on inhibiting crystal growth at low polymer concentrations (0.005%, w/w). The crystal growth inhibitory effect of polymers should be attributable to the retardation of the surface integration of the drug, and such effect should also be polymer and drug dependent. The enhancement of supersaturation level of IND should be attributable to both nucleation and crystal growth inhibition by polymers. The nucleation and crystal growth rate of α-polymorph IND is higher than that of γ-polymorph, and α-polymorph is the predominant form appeared in supersaturated solutions. A rational selection of the appropriate polymer for specific drug is critical for developing supersaturated drug delivery formulations.

Green Synthesis of Carbon Nanotubes-Reinforced Molecularly Imprinted Polymer Composites for Drug Delivery of Fenbufen.

The facile fabrication of single-walled carbon nanotubes (SWCNTs)-doping molecularly imprinted polymer (MIP) nanocomposite-based binary green porogen system, room-temperature ionic liquids (RTILs), and deep eutectic solvents (DESs) was developed for drug delivery system. With fenbufen (FB) as template molecule, 4-vinylpyridine (4-VP) was used as functional monomer, ethylene glycol dimethacrylate as cross-linking monomer, and 1-butyl-3-methylimidazoliumtetrafluoroborate and choline chloride/ethylene glycol as binary green solvent, in the presence of SWCNTs. The imprinting effect of the SWCNT-MIP composites was optimized by regulation of the amount of SWCNTs, ratio of RTILs and DES, and the composition of DES. Blue shifts of UV bands strongly suggested that interaction between 4-VP and FB can be enhanced due to SWCNT doping in the process of self-assembly. The reinforced imprinted effect of CNT-doping MIP can provide superior controlled release characteristics. Compared with the control MIP prepared without SWCNTs, the imprinting factor of the SWCNT-MIP composites exhibited a twofold increase. In the analysis for the FB release kinetics from all samples, the SWCNT-reinforced MIP produced the lowest value of drug diffusivity. The relative bioavailability of the SWCNT-MIP composites (F %) displayed the highest value of 143.3% compared with the commercial FB tablet, whereas the control MIP and SWCNT-non-MIP composites was only 48.3% and 44.4%, respectively. The results indicated that the SWCNT-MIP nanocomposites developed here have potentials as the controlled-release device.

In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.

Comparative Evaluation of Nimesulide-Loaded Nanoparticles for Anticancer Activity Against Breast Cancer Cells.

Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future.

Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders.

Structure-activity relationship of celecoxib and rofecoxib for the membrane permeabilizing activity.

Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory effect by inhibiting cyclooxygenase activity. We previously suggested that in addition to cyclooxygenase-inhibition at the gastric mucosa, NSAID-induced gastric mucosal cell death is required for the formation of NSAID-induced gastric lesions in vivo. We showed that celecoxib exhibited the most potent membrane permeabilizing activity among the NSAIDs tested. In contrast, we have found that the NSAID rofecoxib has very weak membrane permeabilizing activity. To understand the membrane permeabilizing activity of coxibs in terms of their structure-activity relationship, we separated the structures of celecoxib and rofecoxib into three parts, synthesized hybrid compounds by substitution of each of the parts, and examined the membrane permeabilizing activities of these hybrids. The results suggest that the sulfonamidophenyl subgroup of celecoxib or the methanesulfonylphenyl subgroup of rofecoxib is important for their potent or weak membrane permeabilizing activity, respectively. These findings provide important information for design and synthesis of new coxibs with lower membrane permeabilizing activity.

1D and 2D Coordination Polymers of Calcium with Nonsteroidal Anti-Inflammatory Drugs: Synthesis, Crystal Structures, Hirshfeld Surfaces, Antimicrobial and Antioxidant Activities.

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket)2(H2O)2]n (1), [Mg(ket)2(H2O)2] (2), [Ca(ind)2(EtOH)2]n (3), and [Mg(ind)2(EtOH)2] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X-ray diffraction technique T=100 K. The structure of 1 is dominated by a one-dimensional coordination polymer, while 3 is formed by a two-dimensional layer stabilized by the calcium zig-zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram-positive and Gram-negative bacteria as well as yeasts.

ß-Amino acid and amino-alcohol conjugation of a nonsteroidal anti-inflammatory drug (NSAID) imparts hydrogelation displaying remarkable biostability, biocompatibility, and anti-inflammatory properties.

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with ß-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable (1)H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure-property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns).

New flurbiprofen derivatives: synthesis, membrane affinity and evaluation of in vitro effect on ß-amyloid levels.

Alzheimer's disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the disease but, unfortunately, the available treatments often produce no significant clinical benefits. During the last decades compounds that inhibit or modulate γ-secretase, reducing ß amyloid (Aß) levels, have been considered as potential therapeutics for AD. Among these the (R)-enantiomer of flurbiprofen (FLU) seems to be very promising, but it shows low brain penetration. In this study, in order to improve the properties of FLU against Alzheimer's pathogenesis we synthesized some novel FLU lipophilic analogues. Lipophilicity of the new molecules has been characterized in terms of clogP, log K(C18/W) and log K(IAM/W) values. Permeability has been determined in both gastrointestinal PAMPA (PAMPA-GI) at different pH values and in brain blood barrier PAMPA (PAMPA-BBB) models. They were also tested for their ability to inhibit in vitro γ-secretase activity using rat CTXTNA2 astrocytes. Interestingly, the investigated molecules demonstrated to reduce Aß 42 levels without affecting the amyloid precursor protein APP level in a clear concentrations-dependent manner.

N-Amino acid linoleoyl conjugates: anti-inflammatory activities.

Several N-linked amino acid-linoleic acid conjugates were studied for their potential as anti inflammatory agents. The parent molecule, N-linoleoylglycine was tested in an in vivo model, the mouse peritonitis assay where it showed activity in reducing leukocyte migration at doses as low as 0.3mg/kg when administered by mouth in safflower oil. Harvested peritoneal cells produced elevated levels of the inflammation-resolving eicosanoid 15-deoxy-Δ(13,14)-PGJ(2). These results are similar to those obtained in earlier studies with N-arachidonoylglycine. An in vitro model using mouse macrophage RAW cells was used to evaluate a small group of structural analogs for their ability to stimulate 15-deoxy-Δ(13,14)-PGJ(2) production. The d-alanine derivative was the most active while the d-phenylalanine showed almost no response. A high degree of stereo specificity was observed comparing the d and l alanine isomers; the latter being the less active. It was concluded that linoleic acid conjugates could provide suitable templates in a drug discovery program leading to novel agents for promoting the resolution of chronic inflammation.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

Ultrasmall Antioxidant Cerium Oxide Nanoparticles for Regulation of Acute Inflammation.

Cerium oxide nanoparticles (CeONP), having potent antioxidant properties, are highly promising nanomaterials for treatment of diseases in which oxidative stress from excessive reactive oxygen species (ROS) plays a critical role in the pathogenesis and progression. However, most previously reported CeONP formulations were not efficiently cleared from the body, precluding their clinical translation. Herein, we report ultrasmall CeONP that can mitigate activation of macrophages and subsequent acute inflammation. It is found that these CeONP can effectively scavenge reactive species, inhibit macrophage activation, and minimize their recruitment and infiltration to the inflammation site, which lead to alleviation of edema and pain hypersensitivity. Moreover, we demonstrate that CeONP can be effectively excreted from the body within 24 h of systemic administration, minimizing long-term toxicity concerns. Altogether, our findings suggest that CeONP may be explored as both antioxidant and anti-inflammatory agents that can reduce acute inflammation with a better safety profile than existing nanoparticles.

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.

Topical nanocarriers for management of Rheumatoid Arthritis: A review.

Rheumatoid arthritis (RA) is a systemic autoimmune disease manifested by chronic joint inflammation leading to severe disability and premature mortality. With a global prevalence of about 0.3%-1% RA is 3-5 times more prevalent in women than in men. There is no known cure for RA; the ultimate goal for treatment of RA is to provide symptomatic relief. The treatment regimen for RA involves frequent drug administration and high doses of NSAIDs such as indomethacin, diclofenac, ibuprofen, celecoxib, etorcoxib. These potent drugs often have off target effects which drastically decreases patient compliance. Moreover, conventional non-steroidal anti-inflammatory have many formulation challenges like low solubility and permeability, poor bioavailability, degradation by gastrointestinal enzymes, food interactions and toxicity. To overcome these barriers, researchers have turned to topical route of drug administration, which has superior patience compliance and they also bypass the first past effect experienced with conventional oral administration. Furthermore, to enhance the permeation of drug through the layers of the skin and reach the site of inflammation, nanosized carriers have been designed such as liposomes, nanoemulsions, niosomes, ethosomes, solid lipid nanoparticles and transferosomes. These drug delivery systems are non-toxic and have high drug encapsulation efficiency and they also provide sustained release of drug. This review discusses the effect of formulation composition on the physiochemical properties of these nanocarriers in terms of particle size, surface charge, drug entrapment and also drug release profile thus providing a landscape of topically used nanoformulations for symptomatic treatment of RA.

Biocatalytic synthesis and in vitro release of biodegradable linear polyesters with pendant ketoprofen.

Enzyme-catalyzed polycondensation for the synthesis of polyester prodrugs of ketoprofen was reported. Lipase acrylic resin from Candida antarctica (CAL-B) was used to synthesize the linear polyesters with pendent ketoprofen groups based on ketoprofen glycerol ester, poly(ethylene glycol), and divinyl sebacate. The products were characterized by GPC and (1)H NMR. The results indicated that the molecular weight and yields of the polyesters depend on experimental conditions such as temperature and feed ratio. The in vitro study showed that the drug release from the polyester was slow under physiological conditions, which indicated that the polyester could be a promising prodrug with extended pharmacological effects by delayed release of ketoprofen.

Conversion of indomethacin nanosuspensions into solid dosage forms via fluid bed granulation and compaction.

Preparation of pharmaceutical nanosuspensions is a popular technique to increase the dissolution velocity of poorly water-soluble drugs. Subsequent drying into a compaction-ready powder or granule is a critical process due to possible adverse solid characteristics and the risk of growth of nanoparticles. This work evaluated the drying of nanosuspensions via fluid bed granulation with focus on the binder selection and used concentrations, as well as the parameters spray rate and atomization pressure. Design of experiments was used to identify significant parameters. Indomethacin nanosuspensions were prepared by wet media milling and dried on a carrier consisting of lactose, microcrystalline cellulose, and crospovidone with and without additional binder during granulation. Resulting granules were compacted into tablets and their in vitro dissolution performances were characterized. A higher content of binder PVP and a higher spray rate led to less growth of resuspended nanoparticles. Finally, indomethacin nanoparticle tablets showed a superior dissolution performance in contrast to raw indomethacin tablets.

An Anti-Inflammatory Poly(PhosphorHydrazone) Dendrimer Capped with AzaBisPhosphonate Groups to Treat Psoriasis.

Dendrimers are nanosized, arborescent macromolecules synthesized in a stepwise fashion with attractive degrees of functionality and structure definition. This is one of the reasons why they are widely used for biomedical applications. Previously, we have shown that a poly(phosphorhydrazone) (PPH) dendrimer capped with anionic azabisphosphonate groups (so-called ABP dendrimer) has immuno-modulatory and anti-inflammatory properties towards human immune cells in vitro. Thereafter, we have shown that the ABP dendrimer has a promising therapeutic efficacy to treat models of acute and chronic inflammatory disorders in animal models. In these models, the active pharmaceutical ingredient was administered systematically (intravenous and oral administrations), but also loco-regionally in the vitreous tissue. Herein, we assessed the therapeutic efficacy of the ABP dendrimer in the preclinical mouse model of psoriasis induced by imiquimod. The ABP dendrimer was administered in phosphate-buffered saline solution via either systemic injection or topical application. We show that the topical application enabled the control of both the clinical and histopathological scores, and the control of the infiltration of macrophages in the skin of treated mice.