Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism

In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P0.05) of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol

Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology

Association of Polymorphisms of Phase I Metabolizing Genes with Sister Chromatid Exchanges in Occupational Workers Exposed to Toluene Used in Paint Thinners

This study investigated genetic damage in paint workers mainly exposed to toluene as it is a major solvent used in paint thinners. Sister chromatid exchange (SCE) assay was used as biomarker of genotoxicity. Blood samples were collected from 30 paint workers and 30 control subjects matched with respect to age and other confounding factors except for exposure to toluene. SCE frequency was found to be significantly higher in paint workers (4.81 ± 0.92) as compared to control individuals (1.73 ± 0.54) ( < 0.05). We also investigated influence of polymorphisms of CYP2E1 and CYP1A1m2 genes on SCE frequency. Our results showed that there was significant increase in frequencies of SCE among the mutant genotypes of CYP2E1 and CYP1A1m2 as compared to wild genotypes. Our study indicated that long term exposure of toluene can increase genotoxic risk in paint workers

DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES

ABSTRACTObjective: Dissolution test serves as a quality control tool for assessment of drug release from dosage form as well as a research tool to optimize newformulations. The existing guidelines by FDA, EMA, ICH, USP, etc., describe specifications for the dissolution of immediate release as well as modifiedrelease oral dosage form. However, none of them have discussed about the discriminatory potential of the medium to differentiate release profile of twoor more products that are pharmaceutically equivalent. It is pertinent to add here that the pharmaceutical equivalents are not always bioequivalent.Hence, a discriminatory dissolution procedure is a must requirement to differentiate the release behavior of drug from a pharmaceutically equivalentproduct that contains different types and amount of excipient in the formulation. This also becomes more cumbersome when it is desirable forprediction of in vivo behavior of a drug when it is converted into a novel delivery system like nanoparticles. The reason could be the presence ofexcipients used to formulate drug nanoparticles into solid oral dosage form, may change the drug disintegration as well as dissolution behavior, whichultimately may lead to altered bioavailability.Methods: In this study, the nanoparticles of meloxicam were prepared using wet media milling and the milled samples were dried using spray drier.The dried nanoparticles were converted into tablet dosage form by varying the type of diluent. To one batch lactose was used and another one wascontaining dicalcium phosphate (DCP). The assessment of release of meloxicam from these two batches was evaluated in various dissolution media.Results: The study revealed that in all the cases the nanoparticulate tablets of Batch 1 have given increased dissolution profile as compared tomarketed formulation (Muvera), Batch 2 and controlled tablets of meloxicam. This proved that the excipients also play a major role in the releasebehavior of drug otherwise if it was not so, the nanoparticulate tablets of Batch 1 and Batch 2 would have given the same dissolution profile in all thetried media. Batch 1 containing lactose with a higher surface area provided more and rapid wetting of the drug by the dissolution media compared toBatch 2 that contained DCP as a major diluent.®Conclusion: Among all the dissolution media tried to evaluate the discriminatory power and simulation with a biorelevant medium, the biphasicmedium of pH 1.8, 4.8 and 6.8 has promised to simulate with biorelevant media. However, the medium of pH 6.8 has shown the best dissolution profile.Keywords: Solubility, Compendial media, Biphasic media, Dissolution, Meloxicam

INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF PIROXICAM USING LIQUISOLID TECHNIQUE

ABSTRACTObjective: This study revealed formulation of a liquisolid system of poorly soluble piroxicam to enhance its dissolution rate. To formulate a liquisolidsystem loaded with piroxicam, solubility study was carried out in various non-volatile liquids.Methods: In 1 ml of polyethylene glycol (PEG) 600, 100 mg piroxicam was added and stirred with gentle heating. To the above liquid medication, 1 gmicrocrystalline cellulose (MCC) 102 (as MCC has given better results), 1 g Syloid 244 FP, 2 g PEG 4000, 500 mg aerosil 200, and 0.255 g sodium starchglycolate (SSG) (5%) were added and mixed properly. The blend was compressed and subjected for quality control parameters.Results: Among all the non-volatile liquids evaluated, piroxicam was most soluble in PEG 600. Using this as liquid medication, several liquisolid compactswere prepared by varying the ratios of MCC PH 102 as carrier and Syloid 244FP as coating material and evaluated for precompression studies. To furtheraccelerate the release of drug, various additives were added in the formulation. Among them, PEG 4000 has shown better flow as well as compressionproperties. Hence, the final formulation (LS-16B) was prepared using a combination of MCC PH 102, Syloid 244 FP, PEG 4000 and SSG as superdisintegrant.The dissolution studies revealed that about 92.18% drug got released from liquisolid compacts in 120 minutes, whereas only 68.16% release wasobserved for pure piroxicam. X-ray diffraction and scanning electron microscopy images revealed the successful formation of liquisolid system.Conclusion: It was concluded that dissolution rate of poorly soluble piroxicam could be enhanced using liquisolid technique.Keywords: Piroxicam, Polyethylene glycol 600, Microcrystalline cellulose PH 102, Syloid 244 FP, Polyethylene glycol 4000

INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF ACYCLOVIR USING LIQUISOLID FORMULATION

Objective: The objective of this research work is to explore the use of liquisolid technique in enhancement of acyclovir dissolution rate. This current study was planned to assess the impact of different formulation variables, such as non-volatile liquid type and concentrations of acyclovir on its dissolution rates profile. Method: Acyclovir liquisolid tablets were prepared with Tween 60 (liquid vehicle), Microcrystalline cellulose PH 102 (acted as a carrier to turn liquid medication into free-flowing powder) and Syloid XDP (coating material). In vitro, drug dissolution rate of liquisolid formulations of acyclovir was performed and compared with pure acyclovir drug using USP dissolution apparatus (Type II) for 60 min at a paddle speed of 50 rpm and filled with 900 mL of distilled water. Results: The dissolution study showed that 94.1% of the drug was released in 60 min of ratio 10 while only 66% of the pure drug acyclovir was released in 60 min. Hence, present work concluded that the acyclovir dissolution rate profile has been improved with the formation of liquisolid formulations. Conclusion: From the present study, it may be ratified that the drug dissolution rate of acyclovir has been improved with the utilization of liquisolid formulations approach.Â

FORMULATION, SYSTEMATIC OPTIMIZATION, IN VITRO, EX VIVO, AND STABILITY ASSESSMENT OF TRANSETHOSOME BASED GEL OF CURCUMIN

Objectives: The current work presents a formulation of curcumin-loaded transethosome (CRM-TE) in the form of a gel and its characterization.Methods: Thirteen formulations were prepared by varying the concentration of Phospholipon 90G as lipid, ethanol, and ratio of lipid: Span using Box- Behnken Design. The optimized formulation was characterized by vesicle size, entrapment efficiency, drug retention, drug permeation through skin, and morphology. Parameters of CRM-TE were compared to other vesicular systems that include liposomes, ethosomes, and transfersomes. Optimized CRM-TE was incorporated into gels, and comparative evaluation was performed. CRM-TE gel was kept at 5±3°C, 25±3°C, and 40±3°C for 180 days, further evaluated for entrapment efficacy and vesicle size.Results: CRM-TE showed 286.4 nm vesicle size, 61.2% entrapment efficiency, 19.8% drug retention, and 71.3% drug permeation at 24 h in the skin. It was found superior in terms of all the parameters as compared to other vesicular formulations. CRM-TE gel also exhibited best characteristics in terms of entrapment efficiency, drug retention, and drug permeation. CRM-TE gel exhibited better stability at 5±3°C in terms of vesicle size and entrapment efficiency as compared to other storage conditions.Conclusion: CRM-TE gel could offer efficient delivery of curcumin through topical route

INVESTIGATION AND OPTIMIZATION OF FORMULATION PARAMETERS FOR SELFNANOEMULSIFYING DELIVERY SYSTEM OF TWO LIPOPHILIC AND GASTROINTESTINAL LABILE DRUGS USING BOX-BEHNKEN DESIGN

Objective: Present research work aims toward codelivery of two hydrophobic drugs, curcumin (CRM) and duloxetine hydrochloride (DXH) through self-nanoemulsifying drug delivery systems (SNEDDS).Methods: Initially, binary mixture in the ratio of 1:1 was prepared and then loaded into SNEDDS. Box-Behnken design (BBD) was adopted to develop SNEDDS. As per the optimal design, 13 SNEDDS prototypes were prepared. Castor oil, tween-80 and Transcutol P® were used as oil, surfactant, and cosurfactant, respectively. To 1 mL of SNEDDS, 30 mg each of CRM and DXH was loaded (CRM-DXH- SNEDDS).Results: The design revealed that for mean droplet size, polydispersity index (PDI), as well as percentage drug loading, all the three factors, i.e. ratio of oil (a), surfactant (b), and cosurfactant (c) were found to give significant effect. Factor B showed the most significant effect on mean droplet size (y1). In case of PDI (y2), factors B and C exerted maximum influence, whereas, Factor A has shown non-significant effect. For percentage drug loading of drugs (y3 and y4), all the three factors were found to have the most significant effect. The optimized batch of CRM-DXH- SNEDDS having composition castor oil, tween-80, and Transcutol P® in the ratio: 2.17:5.22:2.61, revealed that the mean drug loading (%) of CRM and DXH in an optimized batch of SNEDDS was found to be 87.22±1.87 and 92.32±0.19%, respectively. The mean droplet size, PDI, and zeta potential of formed SNEDDS were observed as 113.14±1.14 nm, 0.20±0.026, and −13.2 mV, respectively.Conclusion: BBD provided optimal formula composition for SNEDDS for obtaining desirable drug loading, emulsion droplet size, and zeta potential

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology

Unravelling the role of nutraceutical supplements in treatment of Parkinson’s Disease

Parkinson’s Disease (PD) causes motor dysfunction that usually begins in the elderly population. The prevalence rate of PD is increasing significantly. Currently available therapies are able to manage the disease, however, they have certain side effects associated with long term usage. Hence, there is a dire need to bring therapies that can offer good treatment to PD with less side effects. Recent research has revealed that food supplements which are specifically rich in antioxidants and vitamins have shown better efficacy against PD with a better safety profile. Hence, the present study focuses on the role of nutraceuticals in treatment of PD. Nutritional supplements targeting PD pathology were explored between 2016 and 2022 through Scopus, google scholar and PubMed. The review deciphered the neuroprotective benefits of vitamins, minerals, natural compounds, and phytochemicals that might procrastinate or help in the prevention of PD’s progression by targeting some of the major pathological mechanisms such as oxidative stress, neuroinflammation, misfolding of alpha-synuclein, and mitochondrial dysfunction. Various studies indicating the potential of nutraceutical supplements are discussed in detail