Bio-tactics for neuroprotection of retinal ganglion cells in the treatment of glaucoma.

Glaucoma, a neurodegenerative disorder is characterized by damage of ganglion cells of retina and also its axons. The manner of progression of disease and retinal ganglion cells death in glaucoma still remains unknown and hence many mechanisms are put forward to understand the disease. Clinical developments have suggested that in every single patient decreasing intraocular pressure (IOP) is not the solution to prevent glaucoma which suggests on the fact that there are other risk factors affecting the disease. The demand for substitute unconventional treatments gives rise to the need to understand the biologically based tactics (bio-tactics) for stopping the progression of disease. Pragmatic findings of past years have supported novelty of inventive molecules with hallmark of neuroprotection in gene therapy. On the other hand, transformation of the latest drugs to clinic has not been of much fruitful substantially for the reason that it lacked dependability while measuring in vivo retinal injury. This as a consequence thwarted the high quality healing possibility of neuroprotectants whether administered single-handedly or given complimentary with other IOP reducing agents. Advancement in research is crucial to grasp the underlying mechanisms concerned with glaucoma and apply it in clinical field to develop neuroprotective agents. In this context, the present review is to bring forth an update on up to date progress in the domain of neuroprotection of retinal ganglion cells for treating glaucoma.

Formulation optimization of etoposide loaded PLGA nanoparticles by double factorial design and their evaluation.

Etoposide is one of the most commonly used drugs in chemotherapy of acute lymphocytic leukemia and acute myelogenous leukaemia. Etoposide has variable oral bioavailability ranging from 24-74% and has terminal half life of 1.5 hours by intravenous route. The conventional parenteral therapy causes inconvenience and pain to the patients as it has to be given through a continuous IV infusion over 24-34 h. The present investigation was aimed at developing etoposide loaded biodegradable nanoparticles which would be a sustained release formulation and replace the conventional therapy of continuous intravenous administration. Nanoparticles were prepared by emulsion solvent evaporation method using high pressure homogenization. The process parameters like homogenization cycles (four) and homogenization pressure (10000 psi) were first optimized using a 3(2) factorial design based on response Y1(mean particle size of 98+/-1nm). Then a 32 factorial design was carried out to study the effect of two independent variables, ratio of drug and polymer (X1) and surfactant concentration (X2) on the two responses to obtain their optimized values, percentage entrapment efficiency (Y2, 83.12+/-8.3%) and mean particle size (Y3, 105+/-5.4 nm) for Etoposide loaded PLGA Nanoparticles. Contour plots and response surface plots showed visual representation of relationship between the experimental responses and the set of input variables. The adequacy of the regression model was verified by a check point analysis. The zeta potential values ranged between -23.0 to -34.2 mV, indicating stability. Sucrose was used as cryoprotectant during lyophilization. DSC and XRD studies indicated that etoposide was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. The electron micrographs showed spherical, discrete and homogenous particles. Drug release study showed that etoposide loaded PLGA nanoparticles sustained release up to 72h. The release from the nanoparticles followed first order kinetics and mechanism of drug release was Fickian. Stability studies indicated that it was best to store nanoparticle formulations in the freeze dried state at 2-8 degrees C where they remained stable in terms of both size and drug content upto three months.