This study reports the development of Vitamin B6 (VitB6) modified pH sensitive charge reversal nanoparticles for efficient intracellular delivery of Doxorubicin (DOX). Herein, VitB6 was conjugated to stearic acid, and the nanoparticles of the lipid were formulated by solvent injection method (DOX-B6-SA-NP). Because of the pK (5.6) of VitB6, DOX-B6-SA-NP showed positive charge and enhanced release of DOX at pH 5. Confocal microscopy illustrated that DOX-B6-SA-NP treatment kept higher DOX accumulation inside the cells than conventional pH insensitive lipid nanoparticles (DOX-SA-NP). The cationic charge of nanoparticles subsequently facilitated the endosomal escape and promoted the nuclear accumulation of DOX. Furthermore, in vitro cytotoxicity, apoptosis, cell cycle arrest, and mitochondrial membrane depolarization studies supported the enhanced efficacy of DOX-B6-SA-NP in comparison to free DOX and DOX-SA-NP. Intravenous pharmacokinetics and biodistribution investigations indicated that pH sensitive nanoparticles can significantly prolong the blood circulation time of DOX in biological system and increase the drug accumulation to tumor site. Consequent to this, DOX-B6-SA-NP also exhibited much enhanced therapeutic efficacy and lower toxicity in tumor-bearing rats compared to free DOX. The reduction in toxicity was confirmed by histological and survival analysis. In conclusion, these results suggest that the VitB6 modified charge reversal nanoparticles can be a novel platform for the successful delivery of anticancer drugs.

Tonsillectomy is one of the commonly performed otolaryngological operations. Despite a range of different techniques post-operative pain remains a major side-effect of this operation. Coblation assisted tonsillectomy is a latest technique of tonsillectomy. This technique is said to be associated with less intra-operative bleeding and less postoperative morbidity. We conducted a study in 100 patients to compare the pain scores between coblation assisted and bipolar diathermy tonsillectomy by FLACC score and Wong Baker scale score. The data so collected was statistically analysed using a t test and p values were calculated. The p value was highly significant (p \ 0.001) for both scores in coblation assisted tonsillectomy 6 h postoperatively and on 1st postoperative day (p \ 0.05). On 7th post-operative day however there was no significant difference in post-operative pain score using FLACC score in both groups but Wong baker scale scores were still significant. We concluded that post-operative pain was less with coblator assisted tonsillectomy as compared to bipolar diathermy tonsillectomy at least in early post-operative period.

We have performed, by open-circuit indirect calorimetry, a total of 1546 measurements of energy expenditure on 142 nonpregnant, pregnant, or lactating Gambian village women. Of the 47 common daily activities measured, only 7 would be classified as moderate according to internationally accepted standards, the remainder being light (ie requiring less than 3.5 kcal/min). This was unexpected since many of the tasks, judged subjectively, appeared quite demanding. Furthermore there was no increase towards the end of pregnancy in the energy cost of a range of activities requiring 1-5 kcal/min and involving a variety of body movements, despite the substantial weight gains observed. Only for walking was there the expected increase in energy expenditure. Although in the past it has been assumed that the heavier pregnant women would require additional energy for activity, no special allowance for this is included in current dietary recommendations. The present results indicate that, for women from the developing world, no allowance is necessary. The finding that most activities were light is also of relevance to total energy requirements in this community.

The objective of research was to develop a novel pH-triggered polymeric nanoparticulate in situ gel (NP-ISG) for ophthalmic delivery of acetazolamide (ACZ) to enhance the conjunctival permeation and precorneal residence time of the formulation by overcoming the limitations of protective ocular barriers. Nanoparticles (NP1--NP12) were developed by nanoprecipitation method and evaluated for pharmacotechnical characteristics including transmission electron microscopy. The optimized formulation, NP10 was dispersed in carbopol 934 P to form nanoparticulate in situ gels (NP-ISG1--NP-ISG5). NP-ISG5 was selected as optimized formulation on the basis of gelation ability and residence time. Ex vivo transcorneal permeation study exhibited significantly higher ACZ permeation from NP-ISG5 (74.50 ± 2.20 mg/cm(2)) and NP10 (93.5 ± 2.25 mg/cm(2)) than eye drops (20.08 ± 3.12 mg/cm(2)) and ACZ suspension (16.03 ± 2.14). Modified Draize test with zero score indicated nonirritant property of NP-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Further, NP-ISG5 when tested for hypotensive effect on intraocular pressure (IOP) in rabbits revealed that NP-ISG5 caused significant decrease in IOP (p < 0.05) in comparison to eye drops. Conclusively, NP-ISG5 may offer intensive management of glaucoma via higher permeation, prolonged precorneal residence time and sustained drug release along with higher in vitro efficacy, safety and patient compliance.

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