Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement.

Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.

Exploring potential of diacerin nanogel for topical application in arthritis: Formulation development, QbD based optimization and pre-clinical evaluation.

Diacerein (DCN) is a chondroprotective agent which shows inadequate oral bioavailability along with gastrointestinal side effects. This study is intended to develop a topical novel DCN delivery system. DCN nanogel was prepared by emulsion solvent diffusion technique. The formulation was optimized by response surface methodology by taking two independent variables, concentration of carbopol 940 and eudragit RSPO and three dependent variables, particle size, % entrapment efficiency (EE) and % drug release at 24 h. The optimized formulation had adequat% EE, % drug release at 24 h and particle size. The particle size for optimized nanogel was 190.3 nm with % EE of 83.51% whereas % drug release at 24 h was found 90.13%. The optimized DCN nanogel was analyzed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (DTIR) and transmission electron microscopy (TEM) studies. The drug release kinetic study has shown that the gel followed Higuchi's model and the diffusion was anomalous in nature. The nanogel was characterized for physical examination, viscosity, homogeneity and stability parameters and the results obtained were found upto the mark. The ex-vivo permeation study data was in correlation with results of in-vitro study. In-vivo anti-arthritic study proved the efficacy of developed formulation for arthritis in Freund's Adjuvant Arthritic model. This research work has proved the significant potential of innovated product for arthritis by topical route, as it overcomes the drawbacks of oral route, highly efficient, sustained and targeted the release of drug without any accumulation and toxicity.

Acaricidal activity and clinical safety of arecoline hydrobromide on calves infested with cattle tick Rhipicephalus microplus (Acari: Ixodidae).

The objective of the present study was to determine the acaricidal activity of arecoline hydrobromide against cattle tick Rhipicephalus microplus infesting calves. in vivo efficacy of arecoline emulsified with polysorbate-80 (2%) was evaluated using ear bag method with the effective dose of 12.5 mg/mL applied on ear pinna of calves infested with ticks. Control group received polysorbate-80 (2%) after larvae infestation, however, reference group received deltamethrin (0.5 %). The experiment was continued for six days (144 h) and treatment of drug was given twice a day. Daily observation of calves was done to count the number of ticks after treatment. Acute dermal toxicity study for test drug was performed on wistar rats. Clinical safety of arecoline was determined by examining hematological profile and skin irritancy assay for calves infested with ticks. Results showed that arecoline significantly (p < 0.01) reduced the number of ticks attached to ear pinna of calves. Fewer number of ticks remained on calves skin at 120 h and 144 h were 8.09 and 6.21, respectively after treatment with arecoline in comparison to control group. Treatment of animals with arecoline hydrobromide significantly (p < 0.01) restored the hematological profile of animals as hemoglobin (Hb) level was 9.01 g/100 mL, PVC was 29.24 %, TEC and TLC were 5.23 and 7.19 106/cumm, respectively as compared to the control group having Hb 9.48 g/100 mL, PVC 31.60 %, TEC 5.64 106/cumm and TLC 7.27 106/cumm. Arecoline showed no toxicity while applied on wistar rats. The drug was mild irritative for an initial 20 min to the calves after that no redness or erythema was seen on the skin of the animals. Thus, arecoline hydrobromide may be an effective alternative to be used as herbal ectoparasiticide for the eradication of R. microplus ticks.

First report on efficacy of Citrus limetta seed oil in controlling cattle tick Rhipicephalus microplus in red Sahiwal calves.

The objective of the study was to evaluate the acaricidal activity of Citrus limetta seed oil (CLO) for controlling the cattle tick Rhipicephalus microplus. C. limetta seeds were collected as a waste product from different juice corners. CLO was obtained after extraction of seeds on soxhlet apparatus using n-hexane as solvent. It was characterized through Gas Chromatography-High Resolution Mass Spectroscopy (GC-HRMS) to determine the presence of active constituents. In vitro bioassays were performed using adult immersion test (AIT) and larval packet test (LPT). In vivo acaricidal efficacy of CLO was performed on red Sahiwal calves using ear bag method. Clinical safety of CLO was evaluated by observing haematological parameters and skin irritancy assay. Results of GC-HRMS showed that mainly fatty acids such as linoleic acid, stearic acid, oleic acid, palmitic acid, and linolenic acid were present in the CLO. CLO in the concentration of 125 mg/mL (CLO8) exhibited 100 % mortality in both AIT and LPT. CLO significantly (p < 0.001) reduced the number of ticks from 35 to 5.05 and 3.24 on 144 h after treatment with CLO7 and CLO8, respectively. CLO was found clinically safe without producing erythema and edema on skin. Haematological parameters such as haemoglobin (11.48 g/100 mL), total leucocytes count (4.32 106/cumm), total erythrocytes count (6.80 106/cumm), and packed cell volume (34.39 %) were normal and controlled. CLO may be used as effective and safe drug therapy for controlling R. microplus ticks.

Rhipicephalus microplus (acari: Ixodidae): Clinical safety and potential control by topical application of cottonseed oil (Gossypium sp.) on cattle.

The present study was performed to determine the acaricidal activity of the cottonseed oil (CSO) against cattle tick Rhipicephalus microplus. CSO was analyzed using Gas Chromatograph with high-resolution Mass Spectrometer (GC-HRMS) to identify the presence of active compounds. In vitro bioassays were performed using larval packet test (LPT) and adult immersion test (AIT) by taking different concentrations of CSO (i.e. 0.1, 0.5, 1.5, 2.5, 5, 7.5, 10 and 12.5%). In vivo acaricidal activity of CSO was evaluated by its topical application on red Sahiwal calves for 144 h. Clinical safety of CSO was evaluated by performing skin irritancy test and examination of hematological profile of calves'. GC-HRMS analysis of CSO revealed the presence of many fatty acids including oleic acid, lauric acid, palmitic acid, stearic acid and other components. Results exhibited that all the concentrations of CSO were effective in reducing the number of ticks and their growth. However, CSO at concentrations of 10% (CSO7) and 12.5% (CSO8) exhibited 100% mortality of R. microplus larvae and adults in LPT and AIT, respectively. In vivo acaricidal assay revealed that CSO7 and CSO8 shown 85% and 89% inhibition of ticks, respectively on calves after 144 h as compared to the control group. CSO was clinically safe on calves' skin with mild erythema up to 20 min. Hematological profile of calves revealed no sign of toxicity after treatment with CSO. Thus, CSO can be used as an alternative and safe drug therapy against R. microplus.

Rheumatiod Arthritis: An Updated Overview of Latest Therapy and Drug Delivery.

Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.

The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.