Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular Drugs.

BACKGROUND: Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB). Multi-drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. METHODS: One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe. Macrophage acts as a reservoir of phagocytic receptors to execute diverse physiological functions as well as to perform defense mechanism. RESULTS: Advances in novel carriers open new era for the treatment of tuberculosis which remains a very substantial global health encumbrance. Different binding receptors especially mannose, folate and scavenger receptors are attractive platform for internalization of therapeutics in alveolar macrophage. Nano-carriers and nano-devices designed after the acquaintance of receptor composition and functioning affords site specific targeting of biodegradable and biocompatible drug delivery systems for the treatment of tuberculosis offering complete cure and patient compliance. CONCLUSION: This chapter encompasses recent studies on nanocarriers and new treatment strategies for tuberculosis. In spite of the budding benefits of nano carriers, many limitations still remain to be overcome such as poor oral stability, instability in circulation, inadequate tissue distribution as well as toxicity to normal cells.

Nanoemulsion-Based Transdermal Drug Delivery System for the Treatment of Tuberculosis.

BACKGROUND: The nanoemulsion based carriers are the most suitable delivery systems for poorly soluble drugs to improve the drugs solubility, permeation of drugs and ultimately increase bioavailability by transdermal therapeutic system. The nanoemulsion for poorly soluble drugs is admirable and offered several advantages over others drug delivery. METHODS: For nanoemulsions formulation, they have to deliver the energetic element at the specific organ with nominal uneasiness. Because of the prevention of hepatic first pass uptake transdermal course excel usual crest and trough plasma shape that usually comfort the administration. The antitubercular drugs relate to the formulation of Poly DL-Lactide-Co-Glycolide nanoparticles having an active substance encapsulated within and that the encapsulated substances are stable with respect to each other. CONCLUSION: The present study aimed to explore the challenges and methods in order to increase the solubility of poorly aqueous soluble drug for improved bioavailability alongwith relative study of toxicity problems related to anti-tubercular drug.

Development and evaluation of anti-malarial bio-conjugates: artesunate-loaded nanoerythrosomes.

Biodegradable cellular carrier has desired properties for achieving effective long-term controlled release of drugs having short half life. To reduce the undesired effects of drug, advanced drug delivery systems are needed which are based on specific cell targeting module. Artesunate (ART) conjugation on nanoerythrosomes (NE) can have controlled delivery to avoid drug leakage, increase the stability, and reduce cost and toxicities. In this study nanosized lipoprotein membrane vesicles bearing ART were prepared by extrusion method. Developed ART-NE conjugate formulations were optimized on the basis of vesicle morphology, size and size distribution, polydispersity index, integrity of membrane, loaded drug concentration, drug leakage, effect of temperature and viscosity, syringeability, in vitro release profile and in vivo plasma concentration estimation studies. Fourier transform infrared (FTIR) spectroscopy reveals that lipid chain order of RBCs are insignificantly affected in moderate conditions after ART loading. The formulated ART-NE carrier revealed non aggregated, uniformly sized particles with smooth surfaces. The maximum drug loading was found to be 25.20 ± 1.3 µg/ml. ART-NE formulation was best fit for zero order kinetics and was found to be capable of controlled release of drug for 8 hrs. ART-NE formulation showed good redispersibility with desirable properties for parenteral administration. Formulation was stable when subjected to stress by centrifugal force of 7500 rpm and could bear turbulence shock of 15 passes from hypodermic needle of size 23 gauges. The ART-NE formulation administered intravenously showed higher plasma concentration compared to free drug signifying not only controlled release but higher rate of in vivo release. The developed formulation exhibited zero order release profile as per kinetic study analysis suggesting the suitability of carrier for the sustained and targeted delivery of ART. The developed ART-NE drug delivery system offers improved pharmacokinetic profile with assurance of increased therapeutic efficacy.

Biodegradable long circulating cellular carrier for antimalarial drug pyrimethamine.

OBJECTIVE: The objective of the present study was to develop targeted engineered nanoerythrosomes based intravenous formulation of antimalarial drug pyrimethamine. MATERIAL AND METHODS: The nanoerythrosomes formulation was developed by sonication method and optimized for effective drug loading at variable drug concentration, surface morphology, viscosity and sedimentation volume. RESULTS: The in vitro drug release of formulated product was found to be delayed after 8 hours, having good stability at 4 ± 1°C and showing controlled in vivo release. Tissue distribution studies showed higher accumulation of drug in the liver (18.71 ± 1.4 µg/ml) (P < 0.05) at 1 hour in case of pyrimethamine-loaded nanoerythrosomes as compared to that in free drug (12.82 ± 0.7 µg/ml). Higher amount of drug, i.e. 14.18 ± 0.9 µg/ml (P < 0.05), was found after 24 hours in the liver in case of pyrimethamine-loaded nanoerythrosomes as compared to free drug concentration of 9.72 ± 0.5 µg/ml). DISCUSSION: Data showed that developed pyrimethamine-loaded nanoerythrosomes hold promise for targeting and controlling the release of drug and for improving treatment of malaria when they are combined with rapid acting antimalarials such as artemisinin. CONCLUSION: A decrease in the concentration of pyrimethamine in kidneys and lungs after 24 hours was observed as compared to that observed after 1 hour, showing no or little involvement of these organs in the clearance of drug-loaded nanoerythrosomes.

Periodontal Status amongst Substance Abusers in Indian Population.

Background. In India there have been limited number of studies on periodontal status among drug addicts, and thus this study aims to assess the Oral hygiene and periodontal status in substance abusers and compare it with non-substance abusers. Methods. A comparative study was conducted to assess the periodontal status in substance abusers. Non-substance abusers were procured from the general population of Bangalore. From the control group 250 non-substance abusers were age and sex matched with the study population of substance abusers. The oral hygiene and periodontal condition of all subjects was assessed using Oral hygiene index- simplified (OHI-S), Russell's periodontal indices and Gingival bleeding index. Results. The mean of OHI-S and Periodontal Index (Russell's Index) scores were higher (2.70 and 3.68, resp.) in substance abusers than the control group (2.45 and 2.59, resp.). The mean Gingival bleeding score was lower (9.69) in substance abusers than the control group (22.7) and found to be statistically significant. A positive correlation found between OHI-S and Russell's periodontal index whereas negative correlation was found between OHI-S and Gingival bleeding in substance abusers. Conclusions. Though the oral hygiene was fair, more periodontal destruction and less of gingival bleeding were observed in substance abusers as compared to control group.