Ramachandra Murthy

Hepatic targeting of Concanavalin A appended myristoyl chitosan nanoparticles containing Epirubicin. Myristoyl chitosan was synthesised by reacting native chitosan with myristoyl chloride and  degree of acylation was determined by Ninhydrin assay. Nanoparticles of chitosan and myristoyl chitosan were prepared by ionic gelation and the method was optimised for processing parameters based on particle size, zeta potential and entrapment efficiency (EE). The nanoparticles of chitosan and myristoyl chitosan were conjugated with concanavalin A by incubation and the conjugation was confirmed by zeta potential measurement. The surface morphology of the optimized formulation was checked with the help of SEM and was further studied for organ distribution studies in Wistar rat model. Myristoyl chitosan synthesised was confirmed by FT-IR studies. Degree of acylation was found out to be 42.2 ± 2.7%. The optimized Con A conjugated nanoparticles prepared by chitosan (Ch17) and myristoyl chitosan (MCh17) was found to be spherical in shape with particle size 244.4nm and 275.8nm, zeta potential of 0.307mV and 0.133mV, entrapment efficiency 45.01±1.32% and 40.10±1.23% respectively. In vitro drug release (PBS 7.4) from Ch17 was 93.02±1.66% and followed Higuchi model, while release from MCh17 was 68.53±2.27% and followed Peppas model. Both the formulation were stable for 1 month at the temperature of 2-8oC. In vivo liver uptake of MCh17 nanoparticles was 93.6±10.11% while it was  87.0±7.55% with Ch17. Epirubicin loaded MCH17 nanoparticle showed high uptake by liver with concomitant reduction in blood level of Epirubicin in comparison to  Ch17 nanoparticles.

Colon specific tablets of Oxaliplatin combined with anti-inflammatory agents, Diclofenac sodium were prepared using guar gum as matrix carriers in varying concentrations from 40% to 65%. The drug combination in the tablet was estimate simultaneously using newly developed and validated UV derivative spectroscopy method. In vitro drug release profile was studied in changing media method, first in 0.1N HCl for two hours followed by 3 hours in phosphate buffer media, pH 7.4 (PB7.4) and in simulated colon fluid (phosphate buffer pH 6.8 added with rat ceacal content) (SCF) for 19 hours. The drug release profiles from PB7.4 and simulated colon fluid were found to be dependent on the gaur gum concentration. Matrix tablets of oxaliplatin and diclofenac sodium combination with 60% w/w Gaur gum showed a total release of ~66% of Oxaliplatin and ~53% of Diclofenac sodium after 24 hrs. The colon tissue homogenate studies conducted after oral administration of the optimized matrix tablet in New Zealand Rabbits showed 156 µg oxaliplatin and 96 µg Diclofenac sodium recovery in 24 hours.  X-ray Images of matrix tablets containing barium sulphate in Rabbit showed tablets to be intact in small intestine (6 hours after administration) but were diffused and spread out in large intestine and colon confirming enzyme mediated erosion of the tablet in these regions.