scholarly journals Investigating the anti-cocaine effects of novel kappa opioid receptor agonists: Behavioural and cellular actions of Salvinorin A analogues

2021 ◽  
Author(s):  
◽  
Amy Ewald
Keyword(s):  
Nucleus Accumbens ◽  
Side Effects ◽  
Ex Vivo ◽  
Late Phase ◽  
Dorsal Striatum ◽  
Kappa Opioid Receptor ◽  
Self Administration ◽  
Duration Of Action ◽  
Drug Seeking

<p>Acute kappa opioid receptor (KOPr) activation by traditional agonists produces antiaddiction properties, but side effects such as sedation and depression prevent their clinical use. The novel KOPr agonist salvinorin A (Sal A), isolated from the plant Salvia divinorum, is a potent and selective KOPr agonist with a unique non-nitrogenous structure. Sal A possesses anti-addiction effects with less side effects than traditional KOPr agonists, but its short duration of action limits its therapeutic usefulness. To test the hypothesis that longer acting structural analogues of Sal A may yield a new class of therapeutics, the anti-cocaine effects of Sal A analogues such as 16-bromosalvinorin A (16-brSal A), ethoxymethyl ether salvinorin B (EOM Sal B), and methoxymethyl ether salvinorin B (MOM Sal B) were evaluated. 16-brSal A (1.0 mg/kg) displayed a longer duration of action in mice compared to Sal A, evidenced using the tail flick test (p<0.05). Both 16-brSal A and EOM Sal B produced dose-dependent decreases in cocaine-induced reinstatement of drug seeking (p<0.05). On the other hand, 16-brSal A (1.0 mg/kg) but not MOM Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity (p<0.05), although both compounds showed no sedative effects in the locomotor activity test in rats. This indicates the superior behavioural anti-cocaine profile of 16-brSal A at its minimum effective dose. These three compounds, together with another analogue that also decreased cocaineinduced drug seeking, β-tetrahydropyran salvinorin B (β-THP Sal B), were screened for typical KOPr-mediated side effects using the minimal effective doses that attenuated drug seeking. MOM Sal B but not EOM Sal B (0.1 mg/kg), β-THP Sal B (1.0 mg/kg), or 16-brSal A produced depressive-like effects in the forced swim test (FST) in rats (p<0.05). However, EOM Sal B displayed a reduction in swimming time coupled with an increase in climbing duration in the FST (p<0.05). On the other hand, β-THP Sal B (p<0.001, between 30 – 45 min) and EOM Sal B (p<0.05, between 15 – 30 min) significantly increased sucrose intake in the rat sucrose self-administration model at different time intervals. 16-brSal A, however, produced no significant changes in natural reward intake measured by sucrose self-administration. The improved behavioural profile of 16-brSal A extended to a lack of anxiogenic effects. No significant anxiety-like behaviour was seen in the light dark or elevated plus maze, although aversion was observed in the conditioned place aversion paradigm (p<0.05). The low incidence of adverse effects of 16-brSal A compared to other iv Sal A analogues in behavioural models prompted additional cellular studies of this KOPr agonist. As the anti-cocaine effects of KOPr agonists have been attributed to their ability to modulate dopamine (DA) levels, 16-brSal A was examined for its ability to regulate dopamine transporter (DAT) function. DAT function was determined in vitro by determining uptake of a fluorescent substrate, ASP+, in HEK-293 cells expressing YFP-DAT and myc-KOPr. Ex vivo studies were also conducted by measuring DA uptake in isolated, minced rat dorsal striatum and nucleus accumbens using rotating disk electrode voltammetry. 16-brSal A significantly increased DAT function in both the in vitro (10 μM) and ex vivo (500 nM) models (p<0.05), an effect that was dependent on extracellular regulated kinase 1/2 (ERK1/2). Since late phase ERK1/2 and p38 kinase activation have been attributed to negative KOPr behavioural responses, the effects of 16-brSal A on these pathways were also examined. Western blotting studies revealed that 16-brSal A selectively activated only the early (5 – 15 min) but not late phase (120 – 180 min) ERK1/2 pathway in HEK-293 cells as well as rat dorsal striatum, prefrontal cortex, and nucleus accumbens (p<0.05). 16-brSal A also produced no significant activation of p38 kinase in the dorsal striatum or prefrontal cortex of rats, although significant phosphorylation was seen in the nucleus accumbens (p<0.05). The ability of 16-brSal A to produce desired behavioural anti-addiction effects with fewer adverse effects, matched with its regulation of KOPr signalling pathways, suggests that it may possibly be a functionally selective agonist that preferentially activates the G-protein signalling pathway at the KOPr. Since understanding the potential use of novel KOPr agonists in different phases of the addiction cycle is crucial to ensure effective administration of therapies, Sal A and 16-brSal A were tested in rats self-administering cocaine on the long access (Sal A) and progressive ratio (Sal A and 16-brSal A) schedules. Although no differences in cocaine responding were seen with KOPr agonist treatment in either paradigms, a higher dose or concurrent infusions of KOPr agonist with cocaine may improve the responses observed. Overall, the novel KOPr agonist, 16-brSal A has excellent potential as a pharmacotherapy due to its anti-cocaine effects and minimal adverse side effect profile. This is the first study to examine in detail the behavioural and cellular actions of 16-brSal A, and supports previous reports of Sal A-derived KOPr agonists as prospective therapeutics for cocaine abuse.</p>

scholarly journals Investigating the anti-cocaine effects of novel kappa opioid receptor agonists: Behavioural and cellular actions of Salvinorin A analogues

2021 ◽  
Author(s):  
◽  
Amy Ewald
Keyword(s):  
Nucleus Accumbens ◽  
Side Effects ◽  
Ex Vivo ◽  
Late Phase ◽  
Dorsal Striatum ◽  
Kappa Opioid Receptor ◽  
Self Administration ◽  
Duration Of Action ◽  
Drug Seeking

<p>Acute kappa opioid receptor (KOPr) activation by traditional agonists produces antiaddiction properties, but side effects such as sedation and depression prevent their clinical use. The novel KOPr agonist salvinorin A (Sal A), isolated from the plant Salvia divinorum, is a potent and selective KOPr agonist with a unique non-nitrogenous structure. Sal A possesses anti-addiction effects with less side effects than traditional KOPr agonists, but its short duration of action limits its therapeutic usefulness. To test the hypothesis that longer acting structural analogues of Sal A may yield a new class of therapeutics, the anti-cocaine effects of Sal A analogues such as 16-bromosalvinorin A (16-brSal A), ethoxymethyl ether salvinorin B (EOM Sal B), and methoxymethyl ether salvinorin B (MOM Sal B) were evaluated. 16-brSal A (1.0 mg/kg) displayed a longer duration of action in mice compared to Sal A, evidenced using the tail flick test (p<0.05). Both 16-brSal A and EOM Sal B produced dose-dependent decreases in cocaine-induced reinstatement of drug seeking (p<0.05). On the other hand, 16-brSal A (1.0 mg/kg) but not MOM Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity (p<0.05), although both compounds showed no sedative effects in the locomotor activity test in rats. This indicates the superior behavioural anti-cocaine profile of 16-brSal A at its minimum effective dose. These three compounds, together with another analogue that also decreased cocaineinduced drug seeking, β-tetrahydropyran salvinorin B (β-THP Sal B), were screened for typical KOPr-mediated side effects using the minimal effective doses that attenuated drug seeking. MOM Sal B but not EOM Sal B (0.1 mg/kg), β-THP Sal B (1.0 mg/kg), or 16-brSal A produced depressive-like effects in the forced swim test (FST) in rats (p<0.05). However, EOM Sal B displayed a reduction in swimming time coupled with an increase in climbing duration in the FST (p<0.05). On the other hand, β-THP Sal B (p<0.001, between 30 – 45 min) and EOM Sal B (p<0.05, between 15 – 30 min) significantly increased sucrose intake in the rat sucrose self-administration model at different time intervals. 16-brSal A, however, produced no significant changes in natural reward intake measured by sucrose self-administration. The improved behavioural profile of 16-brSal A extended to a lack of anxiogenic effects. No significant anxiety-like behaviour was seen in the light dark or elevated plus maze, although aversion was observed in the conditioned place aversion paradigm (p<0.05). The low incidence of adverse effects of 16-brSal A compared to other iv Sal A analogues in behavioural models prompted additional cellular studies of this KOPr agonist. As the anti-cocaine effects of KOPr agonists have been attributed to their ability to modulate dopamine (DA) levels, 16-brSal A was examined for its ability to regulate dopamine transporter (DAT) function. DAT function was determined in vitro by determining uptake of a fluorescent substrate, ASP+, in HEK-293 cells expressing YFP-DAT and myc-KOPr. Ex vivo studies were also conducted by measuring DA uptake in isolated, minced rat dorsal striatum and nucleus accumbens using rotating disk electrode voltammetry. 16-brSal A significantly increased DAT function in both the in vitro (10 μM) and ex vivo (500 nM) models (p<0.05), an effect that was dependent on extracellular regulated kinase 1/2 (ERK1/2). Since late phase ERK1/2 and p38 kinase activation have been attributed to negative KOPr behavioural responses, the effects of 16-brSal A on these pathways were also examined. Western blotting studies revealed that 16-brSal A selectively activated only the early (5 – 15 min) but not late phase (120 – 180 min) ERK1/2 pathway in HEK-293 cells as well as rat dorsal striatum, prefrontal cortex, and nucleus accumbens (p<0.05). 16-brSal A also produced no significant activation of p38 kinase in the dorsal striatum or prefrontal cortex of rats, although significant phosphorylation was seen in the nucleus accumbens (p<0.05). The ability of 16-brSal A to produce desired behavioural anti-addiction effects with fewer adverse effects, matched with its regulation of KOPr signalling pathways, suggests that it may possibly be a functionally selective agonist that preferentially activates the G-protein signalling pathway at the KOPr. Since understanding the potential use of novel KOPr agonists in different phases of the addiction cycle is crucial to ensure effective administration of therapies, Sal A and 16-brSal A were tested in rats self-administering cocaine on the long access (Sal A) and progressive ratio (Sal A and 16-brSal A) schedules. Although no differences in cocaine responding were seen with KOPr agonist treatment in either paradigms, a higher dose or concurrent infusions of KOPr agonist with cocaine may improve the responses observed. Overall, the novel KOPr agonist, 16-brSal A has excellent potential as a pharmacotherapy due to its anti-cocaine effects and minimal adverse side effect profile. This is the first study to examine in detail the behavioural and cellular actions of 16-brSal A, and supports previous reports of Sal A-derived KOPr agonists as prospective therapeutics for cocaine abuse.</p>

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Sodium alginate nanoparticles as a new transdermal vehicle of glucosamine sulfate for treatment of osteoarthritis

2017 ◽  
Vol 9 (3-4) ◽  
Author(s):  
Asmaa S. El-Houssiny ◽  
Azza A. Ward ◽  
Dina M. Mostafa ◽  
Salwa L. Abd-El-Messieh ◽  
Kamal N. Abdel-Nour ◽  
...  
Keyword(s):  
Side Effects ◽  
Surface Charge ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Glucosamine Sulfate ◽  
Suspension Stability ◽  
Rat Skin ◽  
Release Studies ◽  
Vitro Release

AbstractGlucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.

scholarly journals Kappa-opioid receptor-dependent changes in dopamine and affective behavior occur differentially across the nucleus accumbens shell rostro-caudal axis

2020 ◽  
Author(s):  
Breanne E. Pirino ◽  
Mary B. Spodnick ◽  
Andrew T. Gargiulo ◽  
Genevieve R. Curtis ◽  
Jessica R. Barson ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Opioid Receptor ◽  
Dopamine Release ◽  
Neural Circuit ◽  
Ex Vivo ◽  
Kappa Opioid Receptor ◽  
Affective Behavior ◽  
Kappa Opioid ◽  
Affective Behaviors ◽  
The Impact

ABSTRACTNeural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behavior, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behavior using approach-avoidance assays. We report here that activation of KORs in the caudal NAc shell significantly inhibits dopamine release, stimulates novelty-induced rearing behavior, increases avoidance behavior, and reduces locomotor activity. In contrast, activation of KORs in the rostral NAc shell inhibits dopamine release to a lesser extent and instead increases approach behavior. Taken together, these results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and they suggest that this might be due to differences in KOR control over dopamine release.

scholarly journals GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 736 ◽  
Author(s):  
Ian J. Villamagna ◽  
Danielle M. McRae ◽  
Aneta Borecki ◽  
Xueli Mei ◽  
François Lagugné-Labarthet ◽  
...  
Keyword(s):  
Side Effects ◽  
Ex Vivo ◽  
Joint Space ◽  
Peroxisome Proliferator ◽  
Scanning Calorimetry ◽  
Peroxisome Proliferator Activated Receptor ◽  
Force Microscopy ◽  
Young’S Moduli ◽  
Joint Disorder

Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young’s moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.

Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor

1992 ◽  
Vol 70 (6) ◽  
pp. 799-807 ◽  
Author(s):  
C. Brideau ◽  
C. Chan ◽  
S. Charleson ◽  
D. Denis ◽  
J. F. Evans ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Potent Inhibitor ◽  
Ex Vivo ◽  
Late Phase ◽  
Squirrel Monkeys ◽  
Propanoic Acid ◽  
Orally Active

MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). MK-0591 had no effect on rat 5-lipoxygenase. MK-0591 has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs. MK-0591 was a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response). These results indicate that MK-0591 is a potent inhibitor of LT biosynthesis both in vitro and in vivo indicating that the compound will be suitable for assessing the role of leukotrienes in pathological situations.Key words: leukotriene, 5-lipoxygenase, leukotriene inhibitor, bronchoconstriction, inflammation, 5-lipoxygenase activating protein.

scholarly journals Anti-Tumoral and Anti-Angiogenic Effects of Low-Diluted Phenacetinum on Melanoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Camille Fuselier ◽  
Sandrine Quemener ◽  
Eleonore Dufay ◽  
Camille Bour ◽  
Camille Boulagnon-Rombi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Side Effects ◽  
Ex Vivo ◽  
Tumor Model ◽  
Primary Cutaneous Melanoma ◽  
Relieve Pain ◽  
Melanoma Treatment ◽  
Vertical Growth Phase

Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. If primary cutaneous melanoma is mostly treated with a curative wide local excision, malignant melanoma has a poor prognosis and needs other therapeutic approaches. Angiogenesis is a normal physiological process essential in growth and development, but it also plays a crucial role in crossing from benign to advanced state in cancer. In melanoma progression, angiogenesis is widely involved during the vertical growth phase. Currently, no anti-angiogenic agents are efficient on their own, and combination of treatments will probably be the key to success. In the past, phenacetin was used as an analgesic to relieve pain, causing side effects at large dose and tumor-inducing in humans and animals. By contrast, Phenacetinum low-dilution is often used in skin febrile exanthema, patches profusely scattered on limbs, headache, or flushed face without side effects. Herein are described the in vitro, in vivo, and ex vivo anti-angiogenic and anti-tumoral potentials of Phenacetinum low-dilution in a B16F1 tumor model and endothelial cells. We demonstrate that low-diluted Phenacetinum inhibits in vivo tumor growth and tumor vascularization and thus increases the survival time of B16F1 melanoma induced-C57BL/6 mice. Moreover, Phenacetinum modulates the lung metastasis in a B16F10 induced model. Ex vivo and in vitro, we evidence that low-diluted Phenacetinum inhibits the migration and the recruitment of endothelial cells and leads to an imbalance in the pro-tumoral macrophages and to a structural malformation of the vascular network. All together these results demonstrate highly hopeful anti-tumoral, anti-metastatic, and anti-angiogenic effects of Phenacetinum low-dilution on melanoma. Continued studies are needed to preclinically validate Phenacetinum low-dilution as a complementary or therapeutic strategy for melanoma treatment.

scholarly journals Tackling the opioid crisis - development of kappa-opioid receptor peptide agonists for safer analgesic therapy

2021 ◽  
Author(s):  
Rink-Jan Lohman ◽  
Karnaker Reddy Tupally ◽  
Ajit Kandale ◽  
Peter Cabot ◽  
Harendra Parekh
Keyword(s):  
Side Effects ◽  
Opioid Receptor ◽  
Specific Activity ◽  
Opioid Analgesic ◽  
Kappa Opioid Receptor ◽  
Metabolic Stability ◽  
Clinical Translation ◽  
Kappa Opioid

The kappa opioid receptor (KOPr) has exceptional potential as an analgesic target, seemingly devoid of the many peripheral side-effects of Mu receptors. Kappa-selective, small molecule pharmaceutical agents have been developed, but centrally mediated side effects have the limited their clinical translation. Here, we modify an active endogenous Dynorphin peptide with the aim of improving drug-likeness and developing safer KOPr agonists for clinical use. Using rational, iterative design and modern peptide chemistry, we developed a series of potent, selective and metabolically stable peptides from Dynorphin 1-7. Peptides were assessed for cAMP-modulation against Kappa, Mu and Delta opioid receptors, metabolic stability, KOPr specificity and binding, and interrogated for in vitro desensitisation and pERK signalling capability. Finally, lead peptides were evaluated for efficacy in Freund’s complete adjuvant rat model of inflammatory nociception. A library of 70 peptides was synthesised and assessed for pharmacological and metabolic stability factors. At least 10 peptide candidates showed low nanomolar activity (˂50 nM) in a cAMP assay, specificity for KORr, and plasma half-life >60 min, with 6 candidates also stable in trypsin. None of the selected peptides showed pERK activity, with a bias towards cAMP signalling. In vivo, KA305 and KA311 showed anti-nociception opioid receptor-specific activity comparable to morphine and U50 844. These highly potent and metabolically stable peptides are promising opioid analgesic leads for clinical translation. Since they are biased peptide KOPr agonists, it is plausible they lack many of the most significant side effects, such as tolerance, addiction, sedation and euphoria/dysphoria, common to opioid analgesics.

scholarly journals Development of novel bioadhesive niosomal formulation for the transcorneal delivery of moxifloxacin hydrochloride in the treatment of corneal ulcer

2019 ◽  
Vol 10 (3) ◽  
pp. 1874-1882
Author(s):  
Manoj K ◽  
Suhail K
Keyword(s):  
Retention Time ◽  
Bacterial Infections ◽  
Contact Lenses ◽  
Corneal Ulcer ◽  
Ex Vivo ◽  
Eye Drops ◽  
Sustained Drug Release ◽  
Major Drawback ◽  
Duration Of Action

A corneal ulcer is an open sore or epithelial defect with an inflammation of the cornea of the eye. Most of the corneal ulcers are caused by bacterial infections and are common in people who wear contact lenses. Moxifloxacin eye drops are frequently used for the treatment of infectious ulcers. However such formulations have a major drawback, that is the short duration of action and usually, require 4-6 times installation daily. A bioadhesive polymer coated niosomal formulation of moxifloxacin was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency. Niosomes were prepared by solvent injection method using cholesterol and span 60. The coating of the niosomes was done using Carbopol 934or HPMC as a bioadhesive polymer. The mean particle size of bioadhesive niosomes found to be below 200nm. Optimization of the coating was based on in vitro diffusion studies, ex vivo transcorneal permeation studies and bioadhesion studies. The retention time of the formulation was determined by in vitro and ex vivo bioadhesion testing. The antimicrobial assay confirmed the potency of the formulation against the gram-negative organism. The current study revealed that bioadhesive niosomal formulations have longer corneal retention time and have sustained drug release for a period of 24 hours.

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