ABSTRACT
The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory. The batch CP3 was considered as optimum, due to excellent flowability, acceptable aggregation and enhanced solubility. The particle size and size distribution data of selected batch CP3 showed 90% of curcumin particulates having size less than 2.74µm, which may deposit to lungs. Twin Impinger studies showed that 29% of respirable fraction was generated, which could be directly delivered to lungs. The in vitro dissolution data showed many fold increase in dissolution rate. Angiolytic activity and MTT assay of PECTIN-PVP CUR have demonstrated enhancement in the anti-tumor potential, compared to curcumin alone. Altogether, PECTIN-PVP CUR were found suitable for local delivery and enhance its anticancer potential of curcumin.
Subject(s)
Curcumin/chemistry , Curcumin/pharmacology , Drug Carriers/chemistry , Lung Neoplasms/pathology , Pectins/chemistry , Povidone/chemistry , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Particle Size , SolubilityABSTRACT
Obsessive-Compulsive Disorder (OCD) is characterized by absurd, recurrent thoughts (obsessions) followed by certain stereotyped actions (compulsions). 5-Hydroxytryptamine (5-HT) abnormalities may be involved in OCD, and further, cause changes in serotonergic transmission that may have direct or indirect effects on the neuronal firing of other neuromodulators affecting thoughts, feelings and behaviors. Serotonin-related genes that are found in OCD include those coding for the 5-HT transporter (5-HTT) and receptors (5-HT(2A), 5-HT(2B), 5-HT(2C) and 5-HT(1B)) as well the 5-HT enzyme tryptophan hydroxylase. OCD can impair all areas of brain functioning and produce devastating effects on patients and their families. Marble-burying behavior of mice has been employed to study anxiety disorders, including the OCD. The aim of this study was to test the efficacy of aripiprazole and alcohol per se and in combination on marble-burying behavior of mice. A total of 114 male Swiss mice divided in 19 groups were studied. Aripiprazole (0.1 mg/kg, i.p.) per se as well as ethanol (0.1% w/v) per se did not show any anti-compulsive activity. But the combination comprising of ineffective doses of aripiprazole (0.1 mg/kg, i.p.) and ethanol (0.1% w/v) showed significant anti-compulsive activity as reflected by inhibition of marble-burying behavior.
Subject(s)
Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Motor Activity/drug effects , Obsessive-Compulsive Disorder/prevention & control , Piperazines/pharmacology , Quinolones/pharmacology , Analysis of Variance , Animals , Aripiprazole , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Male , Mice , Obsessive-Compulsive Disorder/psychologyABSTRACT
Obsessive-compulsive disorder (OCD) is characterized by absurd, recurrent thoughts (obsessions) followed by certain stereotyped actions (compulsions). OCD can impair all areas of brain functioning and produce devastating effects on patients and their families. Marble-burying behavior of mice is a well-accepted paradigm to screen anti-compulsive activity. The aim of present study was to evaluate the effect of ritanserin and leuprolide per se and in combination on marble-burying behavior of mice. The present study showed that ritanserin (l, 2 and 20 mg kg(-1) i.p.) per se did not show any anti-compulsive effect. Leuprolide (200 and 300 microg kg(-1) s.c.) per se showed anti-compulsive effect, causing statistically significant inhibition of marble-burying behavior of mice. The prior treatment with ritanserin, 5HT(2A/2C) antagonist (20 mg kg(-1) i.p.), has effectively blocked the inhibitory influence of leuprolide (300 microg kg(-1) s.c.) on marble burying behavior of mice, suggesting that leuprolide, a LHRH agonist, also requires serotonin to express its anti-compulsive effect. Further, it also suggested that the effect of leuprolide appears to be mediated through 5HT(2A/2C) receptors.
