Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy

Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapyAnti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironrnental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (similar to 50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system.that offers the possibility to treat different solid tumors by intratumoral administration.Brazilian Fundação de Amparo e Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Additionally, this article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) Project PTDC/SAU-TOX/114549/2009 – FCOMP-01-0124-FEDER-016057, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

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

A novel gastroretentive floating system for zidovudine, based on calcium-silicate beads

The aim of the research effort entertained herein was to develop, evaluate and fully characterize a multiparticulate floating gastroretentive system for the modified release of zidovudine (AZT), an antiretroviral drug. AZT was used as a water-soluble model drug at therapeutic doses. The floating gastroretentive system was obtained via polymer coating of calcium silicate-adsorbed AZT. The proposed system was evaluated in vitro for particle micromorphology, lag time for floating and duration of floating, drug loading capacity, drug release profile, and drug release kinetics. The physicochemical properties of AZT were evaluated by scanning electron microscopy (SEM) analyses, differential scanning calorimetry (DSC) analyses, X-ray diffraction (XRD) analyses, and infrared spectroscopy (FTIR) analyses. Results from SEM analysis of the AZT-containing floating gastroretentive granules allowed observation of an irregular surface and the apparent absence of pores. Floating of the AZT-containing gastroretentive granules was immediately achieved, that is lag time for floating was virtually zero and duration of floating was higher than 12 h. The drug loading capacity of the floating gastroretentive granules was ca. 81.09 ± 14.66%, and the release system thus obtained exhibited an extended drug release profile. Results from DSC and XRD analyses showed a modification in the AZT solid state, while the FTIR spectroscopy analyses revealed that the chemical structure of AZT remained unchanged upon adsorption to calcium silicate followed by polymeric coating. Hence, the coated granules produced presented gastroretentive, floating, and extended drug release properties.Research Scientist fellowship ( FAPESP Ref. No. 2011/51077 - 8 ) is hereby gratefully acknowledged. The authors also wish to thank Nortec Química (Rio de Janeiro RJ, Brazil) for providing the reference materials, and Almapal (São Paulo SP, Brazil) and Cristalia Laboratories (Itapira SP, Brazil) for providing the samples. SAU - FAR: The Portuguese Science and Technology Foundation ( PTDC/SAU - FAR/113100/2009

Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using a single-step deproteinization. Chromatographic separation of zidovudine from interfering components was achieved with a C-18 reverse phase column, a mobile phase consisting of a mixture of sodium acetate buffer (55mM) with pH adjusted to 7.0 and acetonitrile (91:9 v/v) and UV detection set at 265 nm. The method was linear from 100 to 10000 ng.mL"¹ (r² > 0.9995), and zidovudine had a mean recovery from plasma of 92.8%. The coefficient of variation of inter-day and intra-day quality control samples was less than 15%. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC0 24, Cmax, t , t1/2) were determined. The proposed method was found to be simple, specific, accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats

Development and In Vitro Evaluation of Lyotropic Liquid Crystals for the Controlled Release of Dexamethasone

In this study, amphiphilic polymers were investigated as biomaterials that can control dexamethasone (DXM) release. Such materials present interfacial properties in the presence of water and an oily phase that can result in lyotropic liquid crystalline systems (LLCS). In addition, they can form colloidal nanostructures similar to those in living organisms, such as bilayers and hexagonal and cubic phases, which can be exploited to solubilize lipophilic drugs to sustain their release and enhance bioavailability. It was possible to obtain lamellar and hexagonal phases when combining polyoxyethylene (20) cetyl ether (CETETH-20) polymer with oleic acid (OA), N-methylpyrrolidone (P), isopropyl myristate (IM), and water. The phases were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological, textural, and bioadhesion analyses followed by an in vitro release assay. All samples showed elastic behavior in the rheology studies and hexagonal samples containing P and IM showed the highest adhesiveness. The drug release profile of all LLCS presented an average lag time of 3 h and was best fitted to the Korsmeyer-Peppas and Weibull models, with controlled release governed by a combination of diffusion and erosion mechanisms. These systems are potential carriers for DXM and can be explored in several routes of administration, providing potential advantages over conventional pharmaceutical forms

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