Non-ionic surfactant based vesicles (niosomes) for non-invasive topical genetic immunization against hepatitis B.

DNA vaccines are capable of eliciting both humoral as well as cellular immune responses. Liposomes have been widely employed for DNA delivery through topical route; however, they suffer from certain drawbacks like higher cost and instability. In present study, non-ionic surfactant based vesicles (niosomes) for topical DNA delivery have been developed. DNA encoding hepatitis B surface antigen (HBsAg) was encapsulated in niosomes. Niosomes composed of span 85 and cholesterol as constitutive lipids were prepared by reverse phase evaporation method. Prepared niosomes were characterized for their size, shape and entrapment efficiency. The immune stimulating activity was studied by measuring serum anti-HBsAg titer and cyokines level (IL-2 and IFN-gamma) following topical application of niosomes in Balb/c mice and results were compared with naked DNA and liposomes encapsulated DNA applied topically as well as naked DNA and pure recombinant HBsAg administered intramuscularly. It was observed that topical niosomes elicited a comparable serum antibody titer and endogenous cytokines levels as compared to intramuscular recombinant HBsAg and topical liposomes. The study signifies the potential of niosomes as DNA vaccine carriers for effective topical immunization. The proposed system is simple, stable and cost effective compared to liposomes.

Internal jugular vein cannulation in neurosurgical patients: a new approach.

A new approach to internal jugular vein (IJV) cannulation with the head and neck placed in the neutral position is described. The junction of the medial two thirds and lateral one third between the angle of the mandible and symphysis menti is identified. A vertical line is drawn from this point to join another line drawn between the mastoid process and the medial end of the clavicle. The junction is the puncture point. In 120 patients studied, the failure rate was 1.66%, and there were no complications. We propose this technique as a safe and reliable alternative in neurosurgical patients.

RGD-anchored magnetic liposomes for monocytes/neutrophils-mediated brain targeting.

Negatively charged magnetic liposomes were prepared using soya lecithin (Soya PC), cholesterol and phosphatidyl serine (PS) for their preferential presentation to circulating blood phagocytes (monocytes and neutrophils). PS ratio was optimized in terms of drug and magnetite loading, in vitro magnetic responsiveness and ex vivo monocytes/neutrophils uptake. RGD peptide was covalently coupled to the negatively charged liposomes composed of PC, cholesterol, PS and phopsphatidyl ethanolamine (PE) via carbodiimide-mediated coupling. In vivo cellular sorting study under magnetic guard indicated an increase in relative count of neutrophils and monocytes. Results suggest that selective uptake of RGD-anchored magnetic liposomes by these cells imparts them magnetic property. High levels of a model drug diclofenac sodium was quantified in target organ brain. In case of negatively charged uncoated magnetic liposomes brain levels of the drug was 5.95-fold compared to free drug and 7.58-fold in comparison to non-magnetic formulation, while for RGD-coated magnetic liposomes this ratio was 9.1-fold compared to free drug solution, 6.62-fold compared to non-magnetic RGD-coated liposomes and 1.5-fold when compared to uncoated magnetic liposomes. Liver uptake was significantly bypassed (37.2% and 48.3% for uncoated and RGD-coated magnetic liposomes, respectively). This study suggested the potential of negatively charged and RGD-coated magnetic liposomes for monocytes/neutrophils-mediated active delivery of drugs to relatively inaccessible inflammatory sites, i.e. brain. The study opens a new perspective of active delivery of drugs for a possible treatment of cerebrovascular diseases.

Preparation, characterization and in vitro antimicrobial activity of metronidazole bearing lectinized liposomes for intra-periodontal pocket delivery.

Liposomes constructed of egg phosphatidylcholine (EPC), cholesterol (Chol) and stearoylamine (SA) were coated with lectin (Concanavalin-A). These lectinized liposomes were found to retain the ligand binding activity of surface coated concanavalin A (Con-A) as demonstrated by bovine submaxillary mucin (BSM) binding assay. Moreover the ligand specificity of Con-A was maintained even after coating the liposome surface because the presence of competing sugar alpha-methyl mannoside, significantly inhibited the interaction of lectinized liposomes and BSM. The significance of divalent cations for these interactions was studied. The Con-A coating was found to be stable in simulated salivary fluids (SSF, pH 7.2) and under various pH conditions. In vitro targeting studies of lectinized liposomes with gram-negative bacilli (Streptococcus mutans) that harbor in the periodontal pocket (biofilm) demonstrated nearly 100% bacterial growth inhibition (% BGI). The antimicrobial effect was maintained for 360 min. The results were compared with metronidazole bearing plain (protein free/uncoated) liposomes and the free drug at the same dose levels. Mechanisms involved are also discussed. These observations suggest that liposomes coated with lectin (Con-A) were able to maintain the sugar affinity and specificity of the associated ligand and could be targeted to the surface 'glyco-calyx' of bacterial bio-film.

Transport distraction osteogenesis as a method of reconstruction of the temporomandibular joint following gap arthroplasty for post-traumatic ankylosis in children: a clinical and radiological prospective assessment of outcome.

This clinical and radiographic study investigated the use of transport distraction osteogenesis in unilateral temporomandibular joint (TMJ) ankylosis patients. Six patients aged between 4 and 8 years were selected for the study; the mean preoperative maximal inter-incisal opening (MIO) was 3.5mm without lateral and protrusive mandibular movements. The ankylotic mass along with the posterior border of the ascending ramus was exposed via 'lazy-S' incision. A gap arthroplasty was performed, followed by a 'reverse L' osteotomy on the posterior border of the ramus. In-house manufactured extraoral distraction devices were used for this prospective study. Follow-up clinical and radiographic evaluation was carried out for 13-27 months after completion of the activation period. After a mean follow-up of 19 months, the mean MIO was 29.1mm and the lateral and protrusive movements changed from none to slight. Cone beam computed tomography images of all patients showed remodelled neocondyle created by transport distraction osteogenesis with no statistically significant differences observed for average cancellous bone density, trabecular number, and trabecular spacing between the neocondyle of the operated side (test) and the condyle of the non-operated side (control). Neocondyle formation by transport distraction osteogenesis using the in-house distraction device is a promising treatment option for TMJ reconstruction in ankylosis patients.

Mastication and acid secretion.

The gastric acid response and the buffer capacity of the stomach were measured in 30 control subjects and 22 duodenal ulcer patients in response to a masticatory (solid) and a non-masticatory (homogenized) meal having the same chemical composition. The peak acid output values were equal after a masticatory and after a non-masticatory diet in control subjects (masticatory 18.1 +/- 1.2, non-masticatory 15.7 +/- 1.3 mmol/hr) as well as in duodenal ulcer patients (masticatory 35.7 +/- 1.5, non-masticatory 33.7 +/- 1.1 mmol/hr). The buffer capacity of the stomach contents 1 hr after the meal was significantly greater after a masticatory diet than a non-masticatory diet in both controls (14.6 +/- 1.4 and 9.0 +/- 1.9 mmol) and in duodenal ulcer patients (9.5 +/- 1.5 and 7.5 +/- 1.2 mmol). Duodenal ulcer patients had a significantly lower buffer capacity compared with controls. Masticatory diets may play a part in protecting individuals from developing duodenal ulcer.