Zidovudine-poly(l-lactic acid) solid dispersions with improved intestinal permeability prepared by supercritical antisolvent process

A supercritical antisolvent (SAS) process for obtaining zidovudine-poly(l-lactic acid) (PLLA) solid dispersions (SDs) was used to attain a better intestinal permeation of this drug. A 32 factorial design was used, having as independent variables the ratio 3-azido-23-dideoxythymidine (AZT)PLLA and temperature/pressure conditions, as dependent variables the process yield and particle macroscopic morphology. AZTPLLA production batches were carried out by the SAS process, and the resulting products evaluated via scanning electron microscope, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared analyses. From the nine possible combinations of tests performed experimentally, only one combination did not produced a solid. The L3 batch of SD, produced with 1:2 (AZTPLLA) ratio, resulted in a 91.54% yield, with 40% AZT content. Intestinal permeability studies using the AZTPLLA from L3 batch led to an AZT permeability of approximately 9.87%, which was higher than that of pure AZT (3.84%). AZT remained in crystalline form, whereas PLLA remained in semicrystalline form. AZT release is controlled by a diffusion mechanism. It has been demonstrated that it is possible to use PLLA carrier and SAS process to obtain SD, in a single step.Cristalia (Itapira, Brazil) for the kind supply of the reference substance used throughout the research work. Financial support from Fundação de Amparo á Pesquisa do Estado de São Paulo (2013-19300-4; 2012/01333-0; 2011/21219-5), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PROSUP/CAPES) and Finep Inovação e Pesquisa (Finep, Brazil; 01.13.0286.00)

Client needs and satisfaction in an HIV facility

Health care evaluation serves the purpose of monitoring the quality of health care provided by Health Care Providers (HCP), so that health care services can be provided most effectively and efficiently. Patient satisfaction studies are widely used to assess the quality of outpatient care. A client satisfaction study was conducted at an HIV health care facility in Sydney, Australia during 2007-2008. There were three objectives: 1.) To validate a questionnaire for future determination of client satisfaction in HIV health care facilities. 2.) To identify the levels of satisfaction of clients, and investigate any dissatisfaction and unmet needs towards HIV health care. 3.) To provide recommendations for improving client satisfaction levels in HIV health care. This research used a mixed method approach and consisted of two phases. The first phase was a quantitative survey conducted with 166 clients (both HIV positive and negative) at Albion Street Centre (ASC) using a newly-devised questionnaire. Clients were asked to answer demographic questions, rate their levels of satisfaction with each aspect and each HCP category, and provide suggestions for improvement. Quantitative statistical analysis was conducted to obtain a general view of client satisfaction levels. Dissatisfaction and unmet needs of clients were then investigated in-depth in the second phase of the research through qualitative face-to-face semi-structured interviews. Twenty-two clients (both HIV positive and negative) at ASC were interviewed individually and asked about their attitudes, perceptions, and experiences towards their HCP and the HIV health care services received. Thematic analysis was used to categorise and interpret the qualitative data. More than 90% of the clients were satisfied with most of the aspects covered in the survey, with a mean overall satisfaction score of 84 out of 100. Clients were most iii satisfied with the “technical quality” and “interpersonal manner” of the HCP, and were least satisfied with “waiting time” and “availability of HCP”. The HCP category with which the clients has the highest level of satisfaction was “nurses” (86%), followed by “psychologists” (84%), then “doctors” (83%). Clients who were HIV negative, had a full time job, visited ASC less frequently, or did not possess any type of Health Care Card were more satisfied with the services overall. No common dissatisfaction or unmet needs towards HIV health care service were identified. “Technical quality of HCP” and “the relationship with HCP” were the two most important determinants of client satisfaction, which outweighed the inconvenience contributed by the poor availability of HCP and the location of ASC. The maintenance of “confidentiality/privacy” was shown to be fundamental in HIV health care facilities. The multi-disciplinary nature of ASC increased the degree of convenience and satisfaction level among clients. Suggestions for improvement in client satisfaction levels include increasing the attractiveness of the physical environment and the variety of educational reading materials in the waiting area; introducing beverages, and encouraging clients to be involved in their treatment decisions. Health care administrative staff in particular are reminded not to neglect the importance of the availability of HCP, accessibility, and physical environment when establishing a new HIV health care facility. The mixed method approach (quantitative survey and qualitative interviews) proved beneficial. It increased the validity of the findings by assessing client satisfaction levels using more than one method. This enabled clarification of ambiguities noted in the initial survey through probes used in the interviews, and also allowed investigation of the determinants of client satisfaction through understanding their experiences in HIV health care. Future client satisfaction studies would benefit from using this approach

Lipid nanocarriers for hyperproliferative skin diseases

Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD.This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODER/COMPETE)—project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020. The work is also supported by the National Science Centre within the MINIATURA 4 for a single research activity (grant no: 2020/04/X/ST5/00789) and by the START 2021 Program of the Foundation for Polish Science (FNP) granted to Aleksandra Zielínskainfo:eu-repo/semantics/publishedVersio

Disseminated intravascular coagulation in a dog naturally infected by Leishmania (Leishmania) chagasi from Rio de Janeiro - Brazil

Submitted by Repositório Arca ([email protected]) on 2019-04-24T17:16:51Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-09-18T12:45:45Z (GMT) No. of bitstreams: 2 ve_Honse_Carla_etal_INI_2013.pdf: 178617 bytes, checksum: bd0904c23c2e2cf5433d62501d82d92e (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-09-18T12:45:45Z (GMT). No. of bitstreams: 2 ve_Honse_Carla_etal_INI_2013.pdf: 178617 bytes, checksum: bd0904c23c2e2cf5433d62501d82d92e (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Veterinária. Departamento de Patologia Clínica Veterinária. Laboratório Clínico Veterinário. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Vigilância em Leishmaniose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.Background: Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by the activation of intravascular coagulation and excessive fibrin formation. It always occurs in association with other clinical conditions, including parasitic diseases. DIC has been described as a unusual complication in human and canine visceral leishmaniasis. Case presentation: DIC was found in a seven-year-old male mongrel dog naturally infected by Leishmania (Leishmania) chagasi. Haemostasis parameters demonstrated changes in primary and secondary haemostasis and fibrinolysis. Conclusion: DIC is a unusual condition described in canine visceral leishmaniasis and it seems to be associated with several immunological and pathological mechanisms involved in the disease

Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy

Since 1966, rifampicin (RIF) has been considered one of the most potent drugs in the treatment of tuberculosis (TB), which is caused by infection with M. tuberculosis (Mtb). New nanostructured formulations for RIF delivery and alternative routes of administration have been studied as potential forms of treatment. This study evaluates a liquid crystal system for RIF delivery, using alternative drug delivery routes. The systems developed are composed of surfactant, oleylamine, and soy phosphatidylcholine. With the aid of polarized light microscopy, it was possible to determine that the developed systems had a hexagonal mesophase. All systems developed showed non-Newtonian pseudoplasticity and a high degree of thixotropy. Liquid crystal systems with RIF showed an increase in elastic potential, indicating greater mu-coadhesiveness. The evaluation of mucoadhesive forces revealed an increase in the mucoadhesive potential in the presence of mucus, indicating the presence of satisfactory mucoadhesive forces. The 9DR and 10DR liquid crystal systems, when submitted to Differential Scanning Calorimetry analysis, remained structured even at temperatures above 100 °C, showing excellent stability. The developed liquid crystal systems showed a tolerable degree of cytotoxicity and bactericidal potential, for example, the 9DR system demonstrated a reduction in bacterial load after the third day and reached zero CFU on the seventh day of the test. The developed systems were also evaluated in the preclinical model of Mtb-infected mice, using the nasal, sublingual, and cutaneous route for the delivery of RIF associated with a nanostructured liquid crystal system as a possible tool in the treatment of TB

Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: Interactions with mucin and biomembrane models

The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of AH values suggested a strong association of non-coated SiNP and those PEGylated nanopartides coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanopartides can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers. (C) 2015 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP