235 research outputs found
Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma
The aim of this study is to effectively enhance antitumor activities of endostatin by preparing polymeric nanocarriers. NMR and FT-IR spectra confirmed the successful grafting of the CHT-g-PEI and CHT-g-PEI-PEG-NH2 conjugates. SEM micrographs confirmed the shape of endostatin-loaded nanoparticles to be spherical while both TEM and zeta size results showed nanoparticle’s average size to be 100.6 nm having a positively charged surface with zeta potential of 7.95 mV. The concentrations of CHT and TPP as well as the changing pH conditions account for the increased swelling pattern of endostatin-loaded nanoparticles and influenced endostatin release in vitro. PEI increased the overall amine protonation while PEG aggravated endostatin encapsulation and release. Nanoparticles swell and release endostatin at acidic tumor pH of 6.8 compared to physiological pH of 7.4. The native CHT-g-PEI-PEG-NH2 conjugate showed high cytocompatibility above 80% cell viability across tested formulations. Endostatin-loaded nanoparticles showed a significant reduction in cell viability across tested formulations, with 5.32% cell death at 125 μg/mL and 13.36% at 250 μg/mL following 24 hours’ incubation period. Interestingly, more than a fourfold (61.68%) increment in cytotoxicity was observed at nanoparticle concentration of 1000 μg/mL. It was concluded that CHT-g-PEI-PEG-NH2 is an effective cargo for endostatin delivery with antiangiogenic effect in squamous cell carcinoma
Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders
The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Huntington’s disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders’ in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions
A Review on Composite Liposomal Technologies for Specialized Drug Delivery
The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications
The COVID-19 pandemic and environmental health: Lessons learned
Environmental health is historically an overlooked and underrated discipline. The COVID-19 pandemic highlighted the value of environmental health and environmental health professionals (EHPs). EHPs have a unique set of skills and knowledge that were, or could have been, signifi cant in controlling the pandemic. This skill set includes a thorough understanding of legislation and regulations; the ability to conduct human health risk assessment and implement effective risk-control measures; enforcement, communication, and education skills; and a signifi cant understanding of their own local communities. The opportunities for applying the skills of EHPs vary across the world depending on several factors, including legislative and regulatory frameworks in each jurisdiction. Here we present our early evaluation of the unique skills and knowledge base of EHPs and lessons that can be learned from EHP engagement in public health protection. We also argue that local knowledge and engagement need to be recognized as valuable tools in emergency preparedness. In our increasingly globalized world, mechanisms to maintain and value local knowledge are needed, which could be achieved by embedding the “value of local” into policy to ensure that the importance and value of local knowledge are captured. We also advocate for raising awareness of the value of public health, and specifi cally, environmental health.info:eu-repo/semantics/publishedVersio
Pharmacovigilance in children in Camagüey Province, Cuba
Purpose:
Our aim was to describe the adverse drug reactions (ADRs) detected following increased education about pharmacovigilance and drug toxicity in children in Camagüey Province, Cuba.
Methods:
Over a period of 24 months (January 2009 to December 2010), all reports of suspected ADRs in children to the Provincial Pharmacovigilance Centre in Camagüey Province were analysed. ADRs were classified in relation to causality and severity.
Results:
There were 533 reports involving suspected ADRs in children in the period. Almost one third of the reports received were classified as moderate (155, 29%) or severe (10, 2%). There was one fatality in association with the use of ceftriaxone. Vaccines and antibiotics were responsible for most of the ADR reports (392, 74%) and for all ten severe ADRs. After an intensive educational package, both within the community and the Children’s Hospital, the number of reports increased from 124 in 2008 to 161 in 2009 and 372 in 2010. This was equivalent to a reporting rate of 879 and 2,031 reports per million children per year for 2009 and 2010, respectively.
Conclusions:
The incidence of ADRs in children Camagüey Province, Cuba, is greater than previously reported. An educational intervention about pharmacovigilance and drug toxicity in children can improve the reporting of ADRs
In Silico Theoretical Molecular Modeling for Alzheimer’s Disease: The Nicotine-Curcumin Paradigm in Neuroprotection and Neurotherapy
The aggregation of the amyloid-β-peptide (AβP) into well-ordered fibrils has been considered as the key pathological marker of Alzheimer‘s disease. Molecular attributes related to the specific binding interactions, covalently and non-covalently, of a library of compounds targeting of conformational scaffolds were computed employing static lattice atomistic simulations and array constructions. A combinatorial approach using isobolographic analysis was stochastically modeled employing Artificial Neural Networks and a Design of Experiments approach, namely an orthogonal Face-Centered Central Composite Design for small molecules, such as curcumin and glycosylated nornicotine exhibiting concentration-dependent behavior on modulating AβP aggregation and oligomerization. This work provides a mathematical and in silico approach that constitutes a new frontier in providing neuroscientists with a template for in vitro and in vivo experimentation. In future this could potentially allow neuroscientists to adopt this in silico approach for the development of novel therapeutic interventions in the neuroprotection and neurotherapy of Alzheimer‘s disease. In addition, the neuroprotective entities identified in this study may also be valuable in this regard
Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.
The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings
Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery
This paper explores the potential of polyethylene glycol enclatherated pectin-mucin (PEGencl-
PEC:MUC) submicron matrices (SMMs) as an intravaginal drug delivery system
capable of delivering an anti-HIV-1 agent (zidovudine; AZT) over a prolonged duration. A
three factor and three level (33) Box-Behnken statistical design was employed to optimize
the SMMs. Optimized PEG-encl-PEC:MUC SMMs prepared as a stable W/O emulsion
(determined by the degree of reversible colloidal phenomena) were spherical with a mean
particle size of 270.6±5.533nm and mean zeta potential of -34.4±0.539mV. The
microencapsulation of AZT and the hydrogen bonding mediated shielding of AZT by SMMs
was confirmed by Fourier Transform Infrared (FTIR) analysis. The thermochemical
(differential scanning calorimetry and thermogravimetric analysis) data proposed that Ca2+-
based macromolecular ionic crosslinking as well as the intermolecular interactions may be
responsible for the thermal stability of the delivery system. The partially amorphous nature of
drug-loaded SMMs, as confirmed by X-ray diffraction patterns, further strengthened the
matricization of AZT into the pectin-mucin matrix. In vitro drug release studies from the
SMMs showed approximately 91% zidovudine release in simulated vaginal fluid (SVF) and
94% in phosphate buffered saline (PBS) in 24 hours. The mean dissolution time (MDT) of
zidovudine from the SMMs was 5.974 hours. The attainment of required dimensional
structure and drug release profiles from SMMs highlights the potential of their inclusion into a
secondary carrier system for extended and controlled intravaginal stay.National Research Foundation (NRF) of South Africa.http://www.elsevier.com/locate/ijpharm2017-04-30hb2016Chemistr
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