25, which could be attributed to acidic pH. A solution of 1% w/v CaCl2 was found to be strongly irritant whereas OCM-CS NPs showed no irritation. It is likely that the amount of CaCl2 in OCM-CSNPs was insufficient to produce an irritant effect. Another possible explanation could be that CaCl2 molecules are involved in interaction and bound to polymer and not present in free

form, which is likely to reduce their interaction Inhibitors,research,lifescience,medical with the ocular surface. Figure 15 Cumulative HET-CAM scores of controls and test formulations. Values are expressed as mean ± standard deviation, n = 5. Abbreviations: HET-CAM, hen’s egg test chorioallantoic membrane, NaCl, sodium chloride; SDS, sodium dodecyl sulphate; CaCl2 … 3.18. Therapeutic Efficacy Studies in Rabbits The values of the reduction in IOP (mm of Hg) in normotensive albino rabbits after instillation of a 50μL Inhibitors,research,lifescience,medical dose of each NPs formulation as a function of time were Lapatinib compared to marketed formulation [45]. It was observed that

the IOP lowering activity of marketed formulation reached to maximum value of 2.87mm of Hg within 2hr after instillation. This effect markedly decreased and abolished completely within 4h whereas NPs formulation Inhibitors,research,lifescience,medical produced a significant sustained reduction in IOP. DRZ loaded OCM-CSNPs showed pharmacological effect that was sustained up to 8h. The peak effect was observed at the 4th hour with reduction of IOP value by 2.19mm of Hg, which was less than marketed formulation owing to slow release of drug from NPs compared to marketed formulation, whereas DRZ loaded CSNPs showed pharmacological effect, which was sustained up to Inhibitors,research,lifescience,medical 6h. The peak effect was observed at the third hour with reduction of IOP value by 1.91mm of Hg. As shown in Figure 16, developed OCM-CSNPs and CSNPs formulations showed statistically significant response when compared

to the control group. Marketed formulation being solution showed pulse effect due to immediate availability of drug in large concentration. In case Inhibitors,research,lifescience,medical of NPs, drug was embedded/crosslinked in polymer matrix; large concentration of drug was not available immediately to produce the pulse effect. The prolonged duration of action was due to increased mucoadhesion of OCM-CS that interact with mucin effectively compared to CS. The mucoadhesion many phenomenon is independent of tear turnover rate and depends on the mucus turnover rate that is generally more than 15h. Figure 16 (a) Comparative therapeutic efficacy study of the DRZ loaded OCM-CSNPs, CSNPs, marketed formulation and control. (b) Application of ANOVA to efficacy data. Values are expressed as mean ± standard deviation, n = 3. Abbreviations: DRZ, dorzolamide … Hence, developed formulation of DRZ loaded OCM-CSNPs and CSNPs was found to be effective in lowering the IOP of eye when compared to marketed formulation. Thus, OCM-CSNPs showed better efficacy than CSNPs, which was attributed to better mucoadhesion of OCM-CS. 4. Conclusion In this study, OCM-CS was successfully synthesized from CS and characterized.