Functionalization and evaluation of PEGylated Carbon Nanotubes as novel Drug delivery for methotrexate.

Several delivery systems are developed to target methotrexate to cancer tissues with limited success due to low drug loading, size control, toxicity, and scale up and also the cost of formulation. Off late, carbon nanotubes have been projected as a promising carrier for many drugs including anticancer agents. The present work is an attempt to investigate the potentialities of multi-walled carbon nanotubes (MWCNT) as a carrier for targeting methotrexate to cancer tissues. MWCNTs were functionalized using DSPE-mPEG 2000 and was then reacted with methotrexate (MTX) to produce MWCNT-mPEG-MTX conjugate. The conjugate was characterized for particle size, loading efficiency, morphology & rate of drug release. The result indicated that about 2.26 mg of Methotrexate per mg of MWCNTs were loaded with 56.5% entrapment efficiency. Particle size of the MWCNT conjugate was found to be less than 200nm with polydispersity index of 0.286 post lyophilization of the product. The MWCNT conjugate was found to release the drug faster in acidic medium than at neutral pH. However, in both neutral and acidic media, the release was continuous over the period of 48 hours.

Tumor retention and biodistribution studies of etoposide loaded tripalmitin nanoparticles after intratumoral administration in Dalton's Iymphoma tumor bearing mice

The objective of the present work is to study the biodistribution and tumor retention properties of etoposide (anticancer agent) and etoposide loaded tripalmitin nanoparticles (ETPL) after intratumoral administration in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by spray drying technique. The nanoparticles were uniform and possessed 387 nm mean diameter and negative charge with excellent redispersibility in aqueous media. Radiolabeling of etoposide and ETPL nanoparticles with Technetium-99m (99mTc) resulted in complexes with high labeling efficiency and low radiocolloid formation. The labeled complexes showed good in vitro stability as indicated by low transchelation in presence of DTPA and cysteine and stability in human serum. Biodistribution and tumor retention studies were performed for etoposide and ETPL nanoparticles after intratumoral injection in mice bearing Dalton's lymphoma tumor. Etoposide experienced rapid clearance from the tumor, while the disposition of ETPL nanoparticles was slower. The tissue concentrations of ETPL nanoparticles increased with time (i.e. at 6h and 24h post injection) indicating its retention in tumor site for a longer time. Tumor retention of both etoposide and ETPL nanoparticles was studied upto 48h post injection. The tumor concentration of both etoposide and ETPL nanoparticles was high initially (8.57 percent and 41.8 percent injected dose at 0.5h post injection) and decreased with time (0.12 percent and 1.68 percent injected dose at 48h post injection). The concentration of etoposide rapidly declined from the tumor site while the tumor retention of ETPL nanoparticles was significantly higher than free etoposide (P < 0.001) at all the time points studied. The over all many fold higher tumor retention of ETPL nanoparticles (14 folds even at 48h post injection) compared to etoposide, coupled with lower tissue distribution signifies...

Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies.

Lymphatic transport of orally administered drugs.

Several therapeutic molecules such as lipophilic drugs and peptides suffer from the problems of low oral bioavailability. Improvement of their bioavailability and simultaneous prevention of the oral degradation of the prone molecules appears to be a challenge. Lymphatic system, which is responsible for the maintenance of fluid balance, immunity and metastatic spread of cancers, is also found to play a major role in the oral absorption of lipids and lipophilic drugs from intestine. The specialized structure of gut associated lymphoid tissue can be utilized as a gateway for the delivery of particulate systems containing drugs. Even though a large gap has existed in the field of lymphatic drug delivery, the introduction of a large number of lipophilic drugs and peptides has brought a renewed interest of research in this area. In this review, the mechanisms of intestinal lymphatic drug transport, approaches taken for the delivery of macromolecules, lipophilic and peptide drugs, biochemical barriers involved in intestinal drug absorption, and animal models used in the studies of intestinal lymphatic drug transport has been discussed.

Issues related to disability in India: a focus group study.

BACKGROUND: Systematic research into disability has been scarce, especially from India, even though an estimated 5% of the population may have significant disability due to physical disorders. Depression as a common psychiatric disorder affects about 3%-5% of the population. Thus, the impact of disability related to physical, mental and substance use disorders is enormous and it influences resource allocation and policy planning. METHODS: The issues relating to disability were addressed through a qualitative multicentered study. Focus groups were conducted at three sites in Chennai, Bangalore and Delhi on three themes: (i) parity, stigmatization and social participation; (ii) current practices and needs; and (iii) the General Disability Model as proposed by the World Health Organization. The focus groups were homogeneous and included members from six categories of participants: individuals with physical disability, individuals with mental disability, individuals with alcohol/drug-related disability, family members of mentally disabled persons, family members of physically disabled persons and health professionals. In all, 118 groups were conducted with a mean (SD) group size of 8.6 (1.6). RESULTS: Patients with mental and alcohol/drug-related disability were more discriminated against than those with physical disability. Awareness regarding the existing laws and social programmes was uniformly poor across the three centres. Stigmatization was a major reason for under-utilization of the meagre resources available. There was poor awareness of the Disability Act, 1996. The consumers felt more comfortable with the earlier terms of 'handicap' and 'impairment'. CONCLUSIONS: The study has implications for policy planning, clinical decision-making and social behaviour. Awareness of the laws, facilities and programmes needs to be increased, especially regarding the Disability Act, 1996 among consumers as well as health professionals. More disability-friendly facilities are required.

Transesophageal echocardiography for the detection of left atrial thrombus.

We performed transesophageal two-dimensional echocardiography (TEE) and compared its results with those of transthoracic echocardiography (TTE) in a series of 120 patients with rheumatic mitral stenosis (MS). The patients were selected from a pool of 2000 patients of rheumatic heart disease assessed earlier by clinical examination and TTE. The selection criteria for TEE included one or more of the following: 1. Atrial fibrillation, 2. Embolic episode, 3. Before closed mitral valvotomy or balloon mitral valvuloplasty, 4. Large left atrium (LA) and 5. Evidence of clot or spontaneous echo-contrast in LA. The aim was to study the usefulness of TEE as compared to TTE in the detection of thrombus in LA. LA thrombus was imaged in 34/120 TEE studies as compared to 21/120 TTE studies. In 12/13 patients in whom TTE failed, the clot was present in the left atrial appendage (LAA). In the remaining one patient, poor echo window for TTE was responsible. In 2/6 patients with embolic episode, neither TTE nor TEE could document the presence of clot in LA. The procedure of TEE was well tolerated and there were no complications. We conclude that TEE is a safe and valuable adjunct to TTE with better diagnostic ability for the detection of LA thrombus and should be performed in all patients with MS in whom a clot in LA is suspected or needs to be excluded.

Opinion survey of physicians on ethical issues in medical research.

A total of 3622 physicians registered in the Association of Physicians of India were contacted through mail and requested to respond to a semistructured questionnaire pertaining to different aspects of medical ethics, with particular focus on informed consent. Six hundred twenty-nine physicians (17.4%) responded to the questionnaire; 86% of the respondents reported having had no formal training in medical ethics; 49% of the subjects who undertook research obtained oral consent only. Majority of the respondents noted the relevance of ethics in different medical situations, though in certain areas like community health and research using animals ethical issues were felt to be less important. Patients' inability to come for regular follow-up and illiteracy were opined to be the main constraints in obtaining consent. Opinion on the amount of information to be imported to research participants as part of informed consent was at variance with standard guidelines. Physicians who reported having had an orientation course in medical ethics and those with prior research experience were more aware of ethical issues. Majority of the professionals desired for inclusion of ethics in medical curriculum.