Exploring the follicular route for transcutaneous vaccination using nanoparticles

Transcutaneous vaccination refers to the needle-free delivery of vaccines across the skin. In particular, transfollicular vaccination aims to deliver antigens to the abundant peri-follicular antigen presenting cells. Many of the studies conducted to date to explore this route have been done after pre-treating the skin using techniques such as tape stripping. The presented work evaluates the potential of the transfollicular route as a perspective for transcutaneous vaccination using nanoparticles (NPs) without compromising the stratum corneum barrier by any pre-treatment. The results presented in this thesis showed that the model antigen ovalbumin can be delivered via the transfollicular route by encapsulating into polymeric NPs (polylactic-co-glycolide (PLGA) and Chitosan-PLGA), and that immunization by this route is able to elicit the same proliferation of antigen-specific CD4+ T cells as an intramuscular injection of ovalbumin in an adoptive transfer mouse model. Moreover, immune responses generated by this pathway using a conventional mouse model demonstrated that inclusion of an adjuvant (bis-(3\u27,5\u27)-cyclic adenosine monophosphate, c-di-AMP) in the NP formulation is essential to evoke efficient humoral as well as cellular immune responses. Furthermore, a new particulate carrier system (inverse micelles sugar glass NPs) was prepared, which allowed co-encapsulation of adjuvant and antigen, and showed enhanced stability of encapsulated antigen, better follicular uptake, as well as efficient transfollicular vaccination.Transkutane Impfungen ermöglichen eine nadelfreie Anwendung von Impfstoffen. Insbesondere die transfollikuläre Vakzinierung erlaubt es, Antigene direkt zu den antigen-präsentierenden Zellen im perifollikulären Bereich zu bringen. Bei der überwiegenden Zahl bisheriger Studien wurden die Formulierungen auf vorbehandelter Haut (z.B. tape stripping) eingesetzt. Ziel der vorliegenden Arbeit war es, das Potenzial nanopartikulärer Arzneistoffträgersysteme mittels transkutaner Vakzinierung ohne Vorbehandlung der Haut über die transfollikuläre Route zu untersuchen. In den vorgestellten Studien wurde das Modell-Antigen Ovalbumin in nanoskalige Trägersysteme, bestehend aus Polylactid-co-Glycolid- (PLGA) bzw. Chitosan-PLGA, verkapselt. Kutan verabreicht, zeigten diese in einem adoptiven Transfermodel der Maus, dass die Proliferation von antigenspezifischen CD4+ T-Zellen im gleichen Maße hervorgerufen wird wie durch eine klassische intramuskuläre Injektion. Zusätzlich konnte in einem Mausmodel gezeigt werden, dass der Zusatz des Adjuvants (bis-(3\u27,5\u27)-cyclo-Adenosin-Monophosphat, c-di-AMP) zur Arzneistoffträgerformulierung notwendig ist, um eine ausreichende humorale und zelluläre Immunstimulierung hervorzurufen. Neuartige Carriersysteme in Form von glasartigen inversen Mizellen verbesserten die Stabilität des verkapselten Modelantigens, ermöglichten die Co-Verkapslung des Adjuvants, sowie auch die follikuläre Aufnahme und damit eine effiziente transfollikuläre Vakzinierung

Poland syndrome, a rare congenital disorder with no functional deficit: a case report

Poland syndrome is a rare congenital syndrome. Most of the reported cases are sporadic, pattern of genetic inheritance is not known. It is an anomaly in which there is underdeveloped or absent pectoralis major and minor muscles leading to abnormal appearance of chest on the involved side. Most cases are unilateral with minimal functional abnormality in majority of the cases but with major cosmetic concerns for the patient. Surgery is rarely indicated but if required is done mainly for cosmetic purposes. We report a case of Poland syndrome in a young healthy individual as it started becoming evident

Stabilisation of diaphyseal fractures of both bones forearm with limited contact dynamic compression or locked compression plate: comparison of clinical outcomes

Background: The inception of Locking Compression Plate (LCP) has revolutionized fracture management. With their dramatic success for articular fractures, there is a speculation that they might be more appropriate for diaphyseal fractures as well.Methods: In this randomized prospective cohort study, 56 patients with diaphyseal fractures involving both bones of forearm were segregated into two groups based on internal fixation with Limited contact dynamic compression plate (LC-DCP)(n=28) or with Locking compression plate (LCP)(n=26). Clinical and radiological parameters were studied and functional evaluation was done with Disabilities of arm, shoulder, and hand (DASH) score.Results: Andersons’ criteria was employed to categorize the functional results. The mean duration of surgery and time to union were discovered to be less in favor of LCP group although statistically insignificant. No significant differences in two groups with respect to the functional evaluation (range of movement, Andersons’ criteria and DASH score) and complications could be discerned. No incidence of refracture or synostosis was encountered in any of the group. Conclusions: Although LCP is an effective treatment alternative and may have a subtle edge over LC-DCP in the management of these fractures, their supremacy could not be certified. We deduce that surgical planning and expertise rather than the choice of implant are more pivotal for outstanding results

Histoplasmosis, heart failure, hemolysis and haemophagocytic lymphohistiocytosis

Histoplasmosis is an endemic mycosis with global distribution, primarily reported in immunocompromised individuals. A 29-year old immunocompetent male presented with fever, hepatosplenomegaly and pancytopenia. His peripheral blood showed features suggestive of intravascular hemolysis and echocardiography showed features suggestive of pulmonary arterial hypertension. Bone marrow showed yeast with morphology suggestive of Histoplasma capsulatum. Further investigations revealed hyperferritinemia, hypofibrinogenemia and increased triglycerides. With a diagnosis of progressive disseminated histoplasmosis with secondary Haemophagocytic lymphohistiocytosis, he was successfully treated with amphotericin B followed by itraconazole. We report this case to highlight the atypical and rare manifestations of histoplasmosis

Efficacy of short term versus long term antibiotic therapy in preventing deep wound infections in elective orthopaedic surgeries

Background: Comparison of the efficacy of short term (up to 48 hours) versus long term (five days) antibiotic therapy in preventing deep wound infections in elective orthopaedic surgeries.Methods: Two hundred patients of all ages and both sexes were divided into two groups of 100 patients. One group received long term antibiotic treatment consisting of 2 days intra-venous cefoperazone sulbactam 1.5 gm twice daily and intra-venous amikacin 500 mg twice daily followed by 3 days of oral amoxicillin clavulunate 625 mg thrice daily. Other group received short term antibiotic of 2 days intra-venous cefoperazone sulbactam 1.5 gm twice daily and intra-venous amikacin 500 mg twice daily. Comparison of SSI was done with age, sex, BMI, pre-operative haemoglobin, TLC, duration of surgery in both the groups.Results: In group I and group II respectively, average duration of surgery in procedures involving implants was 65.02±27.41 and 59.47±20.27 minutes and non implant related procedures was 53.66±23.97 and 53.74±22.40 minutes. Overall incidence of SSI in Group I and Group II was 14% and 10% respectively. Mean infection in the present study was 12%.Conclusions: It was concluded that in clean orthopaedic elective surgeries short term antibiotics regimen is as effective as long term antibiotics regimen. Continuing antibiotics for more than two days is associated with drug related complications like allergic reactions and gastrointestinal upset, adverse interactions in other drugs, development of resistant organisms and it adds to overall cost of treatment

DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES

ABSTRACTObjective: Dissolution test serves as a quality control tool for assessment of drug release from dosage form as well as a research tool to optimize newformulations. The existing guidelines by FDA, EMA, ICH, USP, etc., describe specifications for the dissolution of immediate release as well as modifiedrelease oral dosage form. However, none of them have discussed about the discriminatory potential of the medium to differentiate release profile of twoor more products that are pharmaceutically equivalent. It is pertinent to add here that the pharmaceutical equivalents are not always bioequivalent.Hence, a discriminatory dissolution procedure is a must requirement to differentiate the release behavior of drug from a pharmaceutically equivalentproduct that contains different types and amount of excipient in the formulation. This also becomes more cumbersome when it is desirable forprediction of in vivo behavior of a drug when it is converted into a novel delivery system like nanoparticles. The reason could be the presence ofexcipients used to formulate drug nanoparticles into solid oral dosage form, may change the drug disintegration as well as dissolution behavior, whichultimately may lead to altered bioavailability.Methods: In this study, the nanoparticles of meloxicam were prepared using wet media milling and the milled samples were dried using spray drier.The dried nanoparticles were converted into tablet dosage form by varying the type of diluent. To one batch lactose was used and another one wascontaining dicalcium phosphate (DCP). The assessment of release of meloxicam from these two batches was evaluated in various dissolution media.Results: The study revealed that in all the cases the nanoparticulate tablets of Batch 1 have given increased dissolution profile as compared tomarketed formulation (Muvera), Batch 2 and controlled tablets of meloxicam. This proved that the excipients also play a major role in the releasebehavior of drug otherwise if it was not so, the nanoparticulate tablets of Batch 1 and Batch 2 would have given the same dissolution profile in all thetried media. Batch 1 containing lactose with a higher surface area provided more and rapid wetting of the drug by the dissolution media compared toBatch 2 that contained DCP as a major diluent.®Conclusion: Among all the dissolution media tried to evaluate the discriminatory power and simulation with a biorelevant medium, the biphasicmedium of pH 1.8, 4.8 and 6.8 has promised to simulate with biorelevant media. However, the medium of pH 6.8 has shown the best dissolution profile.Keywords: Solubility, Compendial media, Biphasic media, Dissolution, Meloxicam

INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF PIROXICAM USING LIQUISOLID TECHNIQUE

ABSTRACTObjective: This study revealed formulation of a liquisolid system of poorly soluble piroxicam to enhance its dissolution rate. To formulate a liquisolidsystem loaded with piroxicam, solubility study was carried out in various non-volatile liquids.Methods: In 1 ml of polyethylene glycol (PEG) 600, 100 mg piroxicam was added and stirred with gentle heating. To the above liquid medication, 1 gmicrocrystalline cellulose (MCC) 102 (as MCC has given better results), 1 g Syloid 244 FP, 2 g PEG 4000, 500 mg aerosil 200, and 0.255 g sodium starchglycolate (SSG) (5%) were added and mixed properly. The blend was compressed and subjected for quality control parameters.Results: Among all the non-volatile liquids evaluated, piroxicam was most soluble in PEG 600. Using this as liquid medication, several liquisolid compactswere prepared by varying the ratios of MCC PH 102 as carrier and Syloid 244FP as coating material and evaluated for precompression studies. To furtheraccelerate the release of drug, various additives were added in the formulation. Among them, PEG 4000 has shown better flow as well as compressionproperties. Hence, the final formulation (LS-16B) was prepared using a combination of MCC PH 102, Syloid 244 FP, PEG 4000 and SSG as superdisintegrant.The dissolution studies revealed that about 92.18% drug got released from liquisolid compacts in 120 minutes, whereas only 68.16% release wasobserved for pure piroxicam. X-ray diffraction and scanning electron microscopy images revealed the successful formation of liquisolid system.Conclusion: It was concluded that dissolution rate of poorly soluble piroxicam could be enhanced using liquisolid technique.Keywords: Piroxicam, Polyethylene glycol 600, Microcrystalline cellulose PH 102, Syloid 244 FP, Polyethylene glycol 4000

DESIGN AND PERFORMANCE VERIFICATION OF NEWLY DEVELOPED DISPOSABLE STATIC DIFFUSION CELL FOR DRUG DIFFUSION/PERMEABILITY STUDIES

Objectives: The present study describes a disposable static diffusion cell for in vitro diffusion studies to achieve better results as compared to well existing Franz diffusion cell (FDC) in terms of the absence of bubbles, variable receptor compartment, ease of handling, and faster results.Materials and Methods: The cell consists of a cup-shaped donor compartment made of semi permeable that could be either cellophane membrane or, animal skin fitted to a rigid frame, which is supported on a plastic plate that contains a hole for the sample withdrawal. The receptor compartment is a separate unit, and it could be any container up to 500ml volume capacity. The most preferred receptor compartment is glass beaker. In the present study, goatskin was used as semi-permeable membrane and verification of its performance was carried out through diffusion studies using gel formulations of one each of the four-selected biopharmaceutical classification system (BCS) class drugs. Metronidazole, diclofenac sodium, fluconazole, and sulfadiazine were used as model drugs for BCS Class I, II, III, and IV, respectively.Results: The newly developed diffusion cell (NDDC) was found to provide faster and more reproducible results as compared to FDC. At the time interval of 24 h, the cell was found to exhibit a higher diffusion of metronidazole, diclofenac sodium, fluconazole, and sulfadiazine by 0.65, 0.65, 0.32, and 0.81 folds, respectively. The faster release obtained with NDDC was attributed to a larger surface area of skin as compared to that in FDC.Conclusion: It was concluded that better reproducibility of results could be achieved with NDDC

Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird

The unique ornamental features and extreme sexual traits of Peacock have always intrigued scientists and naturalists for centuries. However, the genomic basis of these phenotypes are yet unknown. Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch. Genes involved in early developmental pathways including TGF-β, BMP, and Wnt signaling, which have been shown to be involved in feather patterning, bone morphogenesis, and skeletal muscle development, revealed signs of adaptive evolution and provided useful clues on the phenotypes of peacock. Innate and adaptive immune genes involved in complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the predictions of the Hamilton–Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding toward the phenotypic evolution of Indian peacock