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1.
Public Health Pract (Oxf) ; 7: 100468, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38328527

ABSTRACT

Background: Prior to the COVID-19 pandemic, local health departments (LHDs) faced several challenges including underfunding and understaffing. COVID-19 exacerbated these challenges and introduced new ones, including harassment of the agency, staff, and leadership. The objective of this study was to qualitatively understand the experiences and impact of harassment faced by LHDs during the pandemic and provide recommendations to prevent future harassment. Study design: A qualitative study was conducted utilizing focus groups for data collection. Methods: LHDs were sampled from the 2022 National Profile of Local Health Departments (Profile) study to ensure diversity in LHD size. Four virtual focus groups were conducted in Fall 2022 with a total of 16 LHD leaders surveyed in Profile, who were still in their positions. Focus group transcripts were then coded by two independent coders and analyzed using thematic analysis. Findings: Four common domains arose from the data: aggravating factors of harassment, content and formats of harassment, protective factors, and effects on individuals and on the workforce. Conclusion: Findings suggest that harassment was pervasive with many forms and impacts on the LHD leaders and workforce overall. Recommendations are proposed for the local as well as federal partners because the public health system is threatened without immediate, substantial, and coordinated solutions to address harassment and offer protection.

2.
J Esthet Restor Dent ; 36(1): 220-230, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38008797

ABSTRACT

OBJECTIVES: To compare the filler weight percentage (wt%), filler and resin composition, flexural strength, modulus, and hardness of several 3D-printed resins to direct and indirect restorative materials. MATERIALS AND METHODS: Four 3D-printed resins (C&B MFH, Ceramic Crown, OnX, and OnX Tough), one milled resin composite (Lava Ultimate), one conventional composite (Filtek Supreme), and one ceramic (IPS e.max CAD) were evaluated. Filler wt% was determined by the burned ash technique, and filler particle morphology and composition were analyzed by scanning electron microscopy and energy-dispersive spectroscopy, respectively. Organic resin composition was analyzed by Fourier transform infrared spectroscopy. Three-point bend flexural strength and modulus of the materials were determined by ISO 4049 or ISO 6872. Vickers microhardness was measured. Data were compared with a one-way analysis of variance (ANOVA) and Tukey post hoc analysis. Linear regression analysis was performed for filler wt% versus flexural strength, modulus, and hardness. RESULTS: 3D-printed resins were composed of various sized and shaped silica fillers and various types of methacrylate resins. Significant differences were found among filler wt% with some materials around 3% (C&B MFH), others between 33% and 38% (OnX Tough and OnX), others around 50% (Ceramic Crown), and some around 72% (Filtek Supreme and Lava Ultimate). All 3D-printed resins had significantly lower flexural strength, modulus, and hardness than the conventional and milled resin composites and ceramic material (p < 0.001). Filler wt% demonstrated a linear relationship with modulus (p = 0.013, R2 = 0.821) and hardness (p = 0.018, R2 = 0.787) but not flexural strength (p = 0.056, R2 = 0.551). CONCLUSIONS: 3D-printed resins contain from 3% to 50% filler content. Filler wt% alone does not affect flexural strength, but strength may be affected by resin composition as well. Although the 3D-printed resins had lower flexural strength, modulus, and hardness than milled and conventional composite and ceramic, they demonstrated nonbrittle plastic behavior. CLINICAL SIGNIFICANCE: The properties of 3D-printed resins vary based on their composition, which affects their clinical applications.


Subject(s)
Dental Implants , Materials Testing , Surface Properties , Stress, Mechanical , Dental Materials/chemistry , Composite Resins/chemistry , Dental Porcelain/chemistry , Printing, Three-Dimensional , Crowns
3.
Annu Rev Public Health ; 45(1): 359-374, 2024 May.
Article in English | MEDLINE | ID: mdl-38109518

ABSTRACT

The financing of public health systems and services relies on a complex and fragmented web of partners and funding priorities. Both underfunding and "dys-funding" contribute to preventable mortality, increases in disease frequency and severity, and hindered social and economic growth. These issues were both illuminated and magnified by the COVID-19 pandemic and associated responses. Further complicating issues is the difficulty in constructing adequate estimates of current public health resources and necessary resources. Each of these challenges inhibits the delivery of necessary services, leads to inequitable access and resourcing, contributes to resource volatility, and presents other deleterious outcomes. However, actions may be taken to defragment complex funding paradigms toward more flexible spending, to modernize and standardize data systems, and to assure equitable and sustainable public health investments.


Subject(s)
COVID-19 , Public Health , Humans , COVID-19/epidemiology , COVID-19/economics , Financing, Government , Healthcare Financing , Pandemics/economics , Public Health/economics , SARS-CoV-2 , United States
4.
Front Public Health ; 11: 1175661, 2023.
Article in English | MEDLINE | ID: mdl-37771831

ABSTRACT

Objectives: The aim of this study was to collect qualitative data regarding the violence faced by public health officials during the COVID-19 pandemic and create a guideline of recommendations to protect this population moving forward. Methods: Two focus groups were conducted virtually from April 2022 to May 2022. All nine participants were public health officials from across California. A grounded theory approach was used to analyze the data from these focus groups. Results: The main recurrent experiences among public health officials were harassment, psychological impact, systemic backlash, and burnout. Several recommendations for supporting public health officials were highlighted, including security and protection, mental health support, public awareness, and political/institutional support. Conclusion: Our study captures the violent experiences that health officials have faced during the COVID-19 pandemic. To maintain the integrity of the public health system, timely changes must be made to support and protect health officials. Our guideline of recommendations provides a multi-faceted approach to the urgent threats that officials continue to face. By implementing these solutions, we can strengthen our public health system and improve our response to future national emergencies.

5.
J Public Health Manag Pract ; 29(Suppl 1): S45-S47, 2023.
Article in English | MEDLINE | ID: mdl-36223508

ABSTRACT

Since the onset of the COVID-19 pandemic, news and nationwide survey efforts have reported harassment and bullying among local health officials, departments, and personnel, concurrent to a shortage of public health staff in the United States. We examined a nationally representative sample of local public health professionals (LPHPs) from the 2021 Public Health Workforce Interests and Needs Survey (PH WINS) data set to explore reported experiences with harassment, threats, and bullying; self-rated mental and emotional well-being; and intent to leave an organization. Results indicated that experience of harassment was negatively associated with ratings of mental and emotional health and positively associated with an intent to leave an organization. We discuss implications and recommendations to mitigate these risks for the nation's local public health workforce.


Subject(s)
COVID-19 , Public Health , Humans , United States/epidemiology , Public Health/methods , Job Satisfaction , COVID-19/epidemiology , Pandemics , Health Workforce , Surveys and Questionnaires
7.
Appl Radiat Isot ; 174: 109741, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33933840

ABSTRACT

This work focused on the production and purification of the positron emitter 52Mn (t1/2 = 5.6 d) via the natCr(p,n)52Mn reaction, using a TR24 cyclotron and a semi-automated system for the purification of 52Mn. Based on two-column and three-column systems, the recovery of 52Mn was 79.7 ± 6.2% (n = 3) and 70.8 ± 3.3% (n = 3), with processing times of 6.9 ± 0.5 h and 8.2 ± 0.6 h, respectively.

9.
Am J Public Health ; 111(2): 301-308, 2021 02.
Article in English | MEDLINE | ID: mdl-33351657

ABSTRACT

Objectives. To examine correlates of applying for accreditation among small local health departments (LHDs) in the United States through 2019.Methods. We used administrative data from the Public Health Accreditation Board (PHAB) and 2013, 2016, and 2019 Profile data from the National Association of County and City Health Officials to examine correlates of applying for PHAB accreditation. We fit a latent class analysis (LCA) to characterize LHDs by service mix and size. We made bivariate comparisons using the t test and Pearson χ2.Results. By the end of 2019, 126 small LHDs had applied for accreditation (8%). When we compared reasons for not pursuing accreditation, we observed a difference by size for perceptions that standards exceeded LHD capacity (47% for small vs 22% for midsized [P < .001] and 0% for large [P < .001]).Conclusions. Greater funding support, considering differing standards by LHD size, and recognition that service mix might affect practicality of accreditation are all relevant considerations in attempting to increase uptake of accreditation for small LHDs.Public Health Implications. Overall, small LHDs represented about 60% of all LHDs that had not yet applied to PHAB.


Subject(s)
Accreditation/statistics & numerical data , Community Health Centers/statistics & numerical data , Local Government , Public Health Administration/statistics & numerical data , Community Health Centers/standards , Humans , United States
10.
ACS Appl Mater Interfaces ; 12(51): 56792-56804, 2020 Dec 23.
Article in English | MEDLINE | ID: mdl-33306342

ABSTRACT

Radionuclide-functionalized drug delivery vehicles capable of being imaged via positron emission tomography (PET) are of increasing interest in the biomedical field as they can reveal the in vivo behavior of encapsulated therapeutics with high sensitivity. However, the majority of current PET-guided theranostic agents suffer from poor retention of radiometal over time, low drug loading capacities, and time-limited PET imaging capability. To overcome these challenges, we have developed hollow microcapsules with a thin (<100 nm) multilayer shell as advanced theranostic delivery systems for multiday PET tracking in vivo. The 3 µm capsules were fabricated via the aqueous multilayer assembly of a natural antioxidant, tannic acid (TA), and a poly(N-vinylpyrrolidone) (PVPON) copolymer containing monomer units functionalized with deferoxamine (DFO) to chelate the 89Zr radionuclide, which has a half-life of 3.3 days. We have found using radiochromatography that (TA/PVPON-DFO)6 capsules retained on average 17% more 89Zr than their (TA/PVPON)6 counterparts, which suggests that the covalent attachment of the DFO to PVPON provides stable 89Zr chelation. In vivo PET imaging studies performed in mice demonstrated that excellent stability and imaging contrast were still present 7 days postinjection. Animal biodistribution analyses showed that capsules primarily accumulated in the spleen, liver, and lungs with negligible accumulation in the femur, with the latter confirming the stable binding of the radiotracer to the capsule walls. The application of therapeutic ultrasound (US) (60 s of 20 kHz US at 120 W cm-2) to Zr-functionalized capsules could release the hydrophilic anticancer drug doxorubicin from the capsules in the therapeutic amounts. Polymeric capsules with the capability of extended in vivo PET-based tracking and US-induced drug release provide an advanced platform for development of precision-targeted therapeutic carriers and could aid in the development of more effective drug delivery systems.


Subject(s)
Antineoplastic Agents/therapeutic use , Chelating Agents/chemistry , Contrast Media/chemistry , Doxorubicin/therapeutic use , Drug Carriers/chemistry , Neoplasms/drug therapy , Acrylic Resins/chemistry , Acrylic Resins/pharmacokinetics , Animals , Capsules , Chelating Agents/pharmacokinetics , Contrast Media/pharmacokinetics , Deferoxamine/chemistry , Deferoxamine/pharmacokinetics , Drug Carriers/pharmacokinetics , Female , Mice, Inbred BALB C , Positron-Emission Tomography/methods , Povidone/chemistry , Povidone/pharmacokinetics , Precision Medicine/methods , Radioisotopes/chemistry , Tannins/chemistry , Tannins/pharmacokinetics , Ultrasonic Waves , Zirconium/chemistry
11.
Immunohorizons ; 4(9): 530-545, 2020 09 11.
Article in English | MEDLINE | ID: mdl-32917736

ABSTRACT

Efficient T cell activation and effector responses require an antigenic peptide presented on the MHC complex to the TCR (signal 1), costimulatory molecule interactions between T cells and APCs (signal 2), and the synthesis of innate immune-derived proinflammatory cytokines and reactive oxygen species (signal 3). We previously demonstrated that the third signal dissipation impairs autoreactive T cell activation. In this study, we tested the hypothesis that encapsulation of Ag with an antioxidant-containing biomaterial would induce Ag-specific hyporesponsiveness. We cocultured bone marrow-derived dendritic cells with microcapsules composed of multilayer-assembled poly(N-vinylpyrrolidone) (PVPON) and the antioxidant tannic acid (TA). LPS-activated dendritic cells cocultured with (PVPON/TA) microcapsules displayed a decrease in TNF-α, IL-12p70, and CXCL10 synthesis. To study Ag-specific T cell responses, we incorporated chicken OVA into the (PVPON/TA) multilayers and stimulated OT-II splenocytes in a primary recall assay. Flow cytometric analysis demonstrated a significant inhibition of CD4 T cell activation markers, upregulation of CTLA-4 and PD-1, and blunted secretion of IL-2, IFN-γ, TNF-α, and CXCL10 by ELISA. To test microcapsule efficacy in vivo, we immunized OT-II mice with (PVPON/TA)-OVA microcapsules and performed an OVA recall assay. Immunization of OT-II mice with (PVPON/TA)-OVA microcapsules elicited a decrease in CD4 T cell differentiation and effector responses including IFN-γ, TNF-α, CCL3, and CCL5 by ELISA compared with OVA immunization alone. These data show that microcapsules composed of antioxidant and encapsulated Ags can effectively blunt innate immune-derived proinflammatory third signal synthesis necessary for Ag-specific effector T cell responses and present a prospective strategy for T cell-mediated autoimmunity.


Subject(s)
Capsules/pharmacology , Polyphenols/pharmacology , Reactive Oxygen Species/metabolism , T-Lymphocytes/immunology , Animals , Cell Differentiation/immunology , Cytokines/drug effects , Cytokines/immunology , Dendritic Cells/immunology , Flow Cytometry , Lymphocyte Activation , Male , Mice , Mice, Inbred NOD
12.
ACS Appl Polym Mater ; 1(4): 722-736, 2019 Apr 12.
Article in English | MEDLINE | ID: mdl-31828238

ABSTRACT

Nanosized polymeric vesicles (polymersomes) assembled from ABA triblock copolymers of poly(N-vinylcaprolactam)-poly(dimethylsiloxane)-poly(N-vinylcaprolactam) (PVCL-PDMS-PVCL) are a promising platform for biomedical applications, as the temperature-responsiveness of the PVCL blocks enables reversible vesicle shrinkage and permeability of the polymersome shell at elevated temperatures. Herein, we explore the effects of molecular weight, polymer block weight ratios, and temperature on the structure of these polymersomes via electron microscopy, dynamic light scattering, small angle neutron scattering (SANS), and all-atom molecular dynamic methods. We show that the shell structure and overall size of the polymersome can be tuned by varying the hydrophilic (PVCL) weight fraction of the polymer: at room temperature, polymers of smaller hydrophilic ratios form larger vesicles that have thinner shells, whereas polymers with higher PVCL content exhibit interchain aggregation of PVCL blocks within the polymersome shell above 50 °C. Model fitting and model-free analysis of the SANS data reveals that increasing the mass ratio of PVCL to the total copolymer weight from 0.3 to 0.56 reduces the temperature-induced change in vesicle diameter by a factor of 3 while simultaneously increasing the change in shell thickness by a factor of 1.5. Finally, by analysis of the shell structures and overall size of polymersomes with various PVCL weight ratios and those without temperature-dependent polymer components, we bring into focus the mechanism of temperature-triggered drug release reported in a previous study. This work provides new fundamental perspectives on temperature-responsive polymersomes and elucidates important structure-property relationships of their constituent polymers.

13.
Clin Biochem ; 71: 1-13, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31278895

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of antifibrinolytics tranexamic acid (TA), ε-aminocaproic acid (EACA), and aprotinin to decrease overuse of red blood cell transfusions in adult surgical and non-surgical patients. METHODS: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practice (LMBP™) Systematic Review (A-6) method. Eligible studies were assessed for evidence of effectiveness of TA or EACA in reducing the number of patients transfused or the number of whole blood transfusions. RESULTS: Seventy-two articles met LMBP™ inclusion criteria. Fifty-six studies assessed Topical, Intra-articular Injection, or Intravenous TA, 4 studied EACA, and 12 studied the effectiveness of aprotinin. The overall strength of the body of evidence of effectiveness for each of these practices was rated as high. CONCLUSION: LMBP™ recommends the use of topical, intra-articular injection, or intravenous tranexamic acid and the use of ε-aminocaproic acid for reducing overuse of red blood cell transfusion.


Subject(s)
Antifibrinolytic Agents/therapeutic use , Cardiac Surgical Procedures , Erythrocyte Transfusion , Laboratories , Orthopedic Procedures , Practice Guidelines as Topic , Humans
14.
Am J Clin Pathol ; 152(5): 544-557, 2019 10 07.
Article in English | MEDLINE | ID: mdl-31305890

ABSTRACT

OBJECTIVES: Assess support for the effectiveness of two separate practices, restrictive transfusion strategy and computerized physician order entry/clinical decision support (CPOE/CDS) tools, in decreasing RBC transfusions in adult surgical and nonsurgical patients. METHODS: Following the Centers for Disease Control and Prevention Laboratory Medicine Best Practice (LMBP) Systematic Review (A-6) method, studies were assessed for quality and evidence of effectiveness in reducing the percentage of patients transfused and/or units of blood transfused. RESULTS: Twenty-five studies on restrictive transfusion practice and seven studies on CPOE/CDS practice met LMBP inclusion criteria. The overall strength of the body of evidence of effectiveness for restrictive transfusion strategy and CPOE/CDS was rated as high. CONCLUSIONS: Based on these procedures, adherence to an institutional restrictive transfusion strategy and use of CPOE/CDS tools for hemoglobin alerts or reminders of the institution's restrictive transfusion policies are effective in reducing RBC transfusion overuse.


Subject(s)
Decision Support Systems, Clinical , Erythrocyte Transfusion/statistics & numerical data , Medical Order Entry Systems , Medical Overuse/prevention & control , Practice Guidelines as Topic , Humans , Quality Assurance, Health Care
15.
J Public Health Manag Pract ; 25 Suppl 2, Public Health Workforce Interests and Needs Survey 2017: S166-S176, 2019.
Article in English | MEDLINE | ID: mdl-30720629

ABSTRACT

CONTEXT: Although core scientific skills remain a priority to public health, preventing and responding to today's leading causes of death require the workforce to build additional strategic skills to impact the social, community-based, and economic determinants of health. The 2017 Public Health Workforce Interests and Needs Survey allows novel regional analysis of training needs, both individually and across 8 strategic skill domains. OBJECTIVE: The purpose of this article is to describe the training needs of public health staff nationally, across the 10 Department of Health and Human Services Regions. DESIGN: The Public Health Workforce Interests and Needs Survey was a Web-based survey fielded to 100 000 staff nationwide across 2 major frames: state health agency-central office and local health department. State-based respondents were fielded on a census approach, with locals participating in a more complex sampling design. Balanced repeated replication weights were used to address nonresponse and sampling. SETTING: State and local health departments. PARTICIPANTS: Respondents from state and local health departments. MAIN OUTCOME MEASURES: This article draws from the training needs portion of Public Health Workforce Interests and Needs Survey. Descriptive statistics are generated, showing training needs gaps. Inferential analyses pertain to gaps across Region and supervisory status, using Pearson χ test and Rao-Scott design-adjusted χ test. RESULTS: Training needs varied across regions and work setting. Certain strategic skills tended to see larger, consistent gaps regardless of Region or setting, including Budgeting & Finance, Change Management, Systems Thinking, and Developing a Vision for a Healthy Community. CONCLUSIONS: Overall, the data suggest substantial interregional variation in training needs. Until now, this picture has been incomplete; disparate assessments across health departments, Regions, and disciplines could not be combined into a national picture. Regionally focused training centers are well situated to address Region-specific needs while supporting the broader building of capacity in strategic skills nationwide.


Subject(s)
Geographic Mapping , Needs Assessment/classification , Public Health/education , Humans , Needs Assessment/statistics & numerical data , Personnel Staffing and Scheduling/trends , Public Health/statistics & numerical data , Public Health Administration/standards , Public Health Administration/statistics & numerical data , Staff Development/standards , Staff Development/statistics & numerical data , Surveys and Questionnaires , United States
16.
Am J Clin Pathol ; 151(1): 18-28, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30357323

ABSTRACT

Objectives: To evaluate the effectiveness of anemia management and audit with feedback practices in reducing overuse of RBC transfusion. Methods: This review follows the Centers for Disease Control and Prevention's Laboratory Medicine Best Practice Systematic Review (A-6) method. We searched the literature and solicited unpublished studies on practices to reduce overuse of RBC transfusions as measured by reductions in units transfused and proportion of patients transfused. Results: Thirteen studies on preoperative anemia management and three studies on audit feedback practices met inclusion criteria. Strength of evidence was high to moderate for reducing the number of units and proportion of patients transfused. Conclusions: Preoperative anemia management reduces the proportion of patients transfused and units of RBCs transfused. Audit with feedback across cases, physicians, and/or service areas, as part of a continuous quality improvement practice, reduces the proportion of patients and units of RBCs transfused.


Subject(s)
Anemia/therapy , Erythrocyte Transfusion/statistics & numerical data , Practice Guidelines as Topic , Practice Patterns, Physicians' , Feedback , Humans , Medical Audit , Medical Overuse , Physicians , Preoperative Care , Transfusion Medicine
17.
J Public Health Manag Pract ; 24(6): 571-577, 2018.
Article in English | MEDLINE | ID: mdl-29521851

ABSTRACT

CONTEXT: Assessing training needs of the public health workforce is crucial for creating professional development opportunities to improve knowledge, competence, and effectiveness of this workforce. DISSEMINATION: Regional Public Health Training Centers (RPHTCs) assess workforce training needs and deliver training based on identified needs. To determine training priorities, several needs assessment surveys have been administered by RPHTCs and national public health member organizations. EVALUATION: This study identified the types of training questions being asked to public health practitioners in the various assessment surveys implemented by RPHTCs and national membership organizations. Although the surveys measured similar overarching constructs, multiple approaches with limited consistency were used to measure training needs. DISCUSSION: Although successful in responding to the needs of their targeted constituents, the limited consistency among survey types makes generalization of findings difficult. Disseminating common metrics and aggregate survey findings would increase efficiency in determining workforce training needs and developing targeted training.


Subject(s)
Needs Assessment/statistics & numerical data , Public Health/education , Humans , Public Health/statistics & numerical data , Staff Development/methods , Staff Development/standards , Staff Development/statistics & numerical data , Surveys and Questionnaires
18.
Polymers (Basel) ; 10(12)2018 Dec 05.
Article in English | MEDLINE | ID: mdl-30961267

ABSTRACT

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.

19.
Adv Exp Med Biol ; 1009: 239-262, 2017.
Article in English | MEDLINE | ID: mdl-29218564

ABSTRACT

The sub-nanometer scale provided by small angle neutron and X-ray scattering is of special importance to pharmaceutical and biomedical investigators. As drug delivery devices become more functionalized and continue decreasing in size, the ability to elucidate details on size scales smaller than those available from optical techniques becomes extremely pertinent. Information gathered from small angle scattering therefore aids the endeavor of optimizing pharmaceutical efficacy at its most fundamental level. This chapter will provide some relevant examples of drug carrier technology and how small angle scattering (SAS) can be used to solve their mysteries. An emphasis on common first-step data treatments is provided which should help clarify the contents of scattering data to new researchers. Specific examples of pharmaceutically relevant research on novel systems and the role SAS plays in these studies will be discussed. This chapter provides an overview of the current applications of SAS in drug research and some practical considerations for selecting scattering techniques.


Subject(s)
Capsules/chemistry , Drug Delivery Systems/methods , Drugs, Investigational/chemistry , Nanoparticles/chemistry , Scattering, Small Angle , Animals , Data Collection/statistics & numerical data , Data Interpretation, Statistical , Humans , Micelles , Molecular Conformation , Nanoparticles/ultrastructure , Neutron Diffraction/instrumentation , Neutron Diffraction/methods , X-Ray Diffraction/instrumentation , X-Ray Diffraction/methods
20.
Biomacromolecules ; 18(8): 2552-2563, 2017 Aug 14.
Article in English | MEDLINE | ID: mdl-28700211

ABSTRACT

We report a versatile synthesis for polyphenolic polymersomes of controlled submicron (<500 nm) size for intracellular delivery of high and low molecular weight compounds. The nanoparticles are synthesized by stabilizing the vesicular morphology of thermally responsive poly(N-vinylcaprolactam)n-b-poly(N-vinylpyrrolidone)m (PVCLn-PVPONm) diblock copolymers with tannic acid (TA), a hydrolyzable polyphenol, via hydrogen bonding at a temperature above the copolymer's lower critical solution temperature (LCST). The PVCL179-PVPONm diblock copolymers are produced by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization of PVPON using PVCL as a macro-chain transfer agent. The size of the TA-locked (PVCL179-PVPONm) polymersomes at room temperature and upon temperature variations are controlled by the PVPON chain length and TA:PVPON molar unit ratio. The particle diameter decreases from 1000 to 950, 770, and 250 nm with increasing PVPON chain length (m = 107, 166, 205, 234), and it further decreases to 710, 460, 290, and 190 nm, respectively, upon hydrogen bonding with TA at 50 °C. Lowering the solution temperature to 25 °C results in a slight size increase for vesicles with longer PVPON. We also show that TA-locked polymersomes can encapsulate and store the anticancer drug doxorubicin (DOX) and higher molecular weight fluorescein isothiocyanate (FITC)-dextran in a physiologically relevant pH and temperature range. Encapsulated DOX is released in the nuclei of human alveolar adenocarcinoma tumor cells after 6 h incubation via biodegradation of the TA shell with the cytotoxicity of DOX-loaded polymersomes being concentration-dependent. Our approach offers biocompatible and intracellular degradable nanovesicles of controllable size for delivery of a variety of encapsulated materials. Considering the particle monodispersity, high loading capacity, and a facile two-step aqueous assembly based on the reversible temperature-responsiveness of PVCL, these polymeric vesicles have significant potential as novel drug nanocarriers and provide a new perspective for fundamental studies on thermo-triggered polymer assemblies in solutions.


Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/drug therapy , Antineoplastic Agents , Caprolactam/analogs & derivatives , Doxorubicin , Drug Carriers , Lung Neoplasms/drug therapy , Polymers , Polyphenols , Povidone , A549 Cells , Adenocarcinoma, Bronchiolo-Alveolar/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Caprolactam/chemistry , Caprolactam/pharmacokinetics , Caprolactam/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Hot Temperature , Humans , Lung Neoplasms/metabolism , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Polyphenols/chemistry , Polyphenols/pharmacokinetics , Polyphenols/pharmacology , Povidone/chemistry , Povidone/pharmacokinetics , Povidone/pharmacology
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