Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems

Importance of the field: The advancement in material design and engineering has led to the rapid development of new materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review: The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literature published after the 1990s. The release kinetics of selected drug compounds from various material systems is discussed in case studies. Recent progress in the mathematical models based on different transport mechanisms is highlighted. What the reader will gain: This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message: Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. © 2010 Informa UK Ltd.Link_to_subscribed_fulltex

In situ forming poly(ethylene glycol)-based hydrogels via thiol-maleimide Michael-type addition

The incorporation of cells and sensitive compounds can be better facilitated without the presence of UV or other energy sources that are common in the formation of biomedical hydrogels such as poly(ethylene glycol) hydrogels. The formation of hydrogels by the step-growth polymerization of maleimide- and thiol-terminated poly(ethylene glycol) macromers via Michael-type addition is described. The effects of macromer concentration, pH, temperature, and the presence of biomolecule gelatin on gel formation were investigated. Reaction kinetics between maleimide and thiol functional groups were found to be rapid. Molecular weight increase over time was characterized via gel permeation chromatography during step-growth polymerization. Swelling and degradation results showed incorporating gelatin enhanced swelling and accelerated degradation. Increasing gelatin content resulted in the decreased storage modulus (G′). The in vitro release kinetics of fluorescein isothiocyanate (FITC)-labeled dextran from the resulting matrices demonstrated the potential in the development of novel in situ gel-forming drug delivery systems. Moreover, the resulting networks were minimally adhesive to primary human monocytes, fibroblasts, and keratinocytes thus providing an ideal platform for further biofunctionalizations to direct specific biological response. Copyright © 2011 Wiley Periodicals, Inc.Link_to_subscribed_fulltex

Drug release kinetics and transport mechanisms from semi-interpenetrating networks of gelatin and poly(ethylene glycol) diacrylate

Purpose: To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading density have been investigated. Materials and Methods: sIPNs of following gelatin/PEGdA weight-to-weight ratios were prepared: 10:15, 10:20, 10:30, 15:15, 20:15. Five model solutes of different physicochemical properties were selected, i.e. silver sulfadiazine (AgSD), bupivacaine hydrochloride (Bup), sulfadiazine sodium (NaSD), keratinocyte growth factor (KGF), and bovine serum albumin conjugated with fluorescein isothiocyanate (BSA-FITC). Release studies were performed and the results were analyzed using three hydrogel based common theories (free volume, hydrodynamic and obstruction). Results: The release kinetics of model solutes was influenced by each factor under investigation. Specifically, the initial release rates and intra-gel diffusivity decreased with increasing PEGdA content or increasing solute molecular weight. However, the initial release rate and intra-gel diffusivity increased with increasing gelatin content or increasing solute water solubility, which contradicted with the classical hydrogel based solute transport theories, i.e. increasing polymer volume leads to decreased solute diffusivity within the gel. Conclusion: This analysis provides structure-functional information of the sIPN as a potential therapeutic delivery matrix. © 2009 Springer Science+Business Media, LLC.Link_to_subscribed_fulltex

Detecção in situ de citocinas de perfil TH1 e TH2 por imunoistoquímica e relação com a atividade de macrófagos nas formas polares da doença de Hansen

Leprosy is an infectious disease that has a slow and progressive evolution, with high incidence and prevalence in the states that compose the Legal Amazon. Considering the number of cases, the Pará state plays a prominent role in the national context. In order to evaluate the cytokine profile and the macrophages activity in the polar forms of leprosy and correlate with their histopathological aspects, a transversal study was performed, with a sample of 29 patients who had one of the polar forms of leprosy, namely tuberculoid or virchowian, from who skin biopsies of leprosy lesions were taken. It could be observed, through the analysis of this immunohistochemical material, that the studied groups showed no significant variation in the levels of IL-10, TGF-β, CD68, iNOS and Lysozyme. The levels of IL-4 were not expressive in the analyzed tissues and the levels of IFN-γ were higher in patients in the MHV group. In the virchowian pole, all cytokines tended towards a negative correlation with the macrophages activity. In the tuberculoid pole, the level of IL-10 showed a negative correlation with the levels of iNOS, IFN-γ and lysozyme, indicating a macrophage activity inhibition for this cytokine. It can be concluded that there is no difference in cytokine expression of TH1 and TH2 profile in polar forms of Hansen's disease and cytokines have a tendency to negative correlation with the activity of macrophages in MHV pole and a tendency to positive correlation in the pole MHT. Further research is needed to clarify why some populations have more susceptibility to leprosy than others. A similar study with a larger number of individuals may have a more significant outcome.A hanseníase é uma doença infecto-contagiosa, de evolução lenta e progressiva, com grande incidência e prevalência nos estados que compõem a Amazônia legal onde o Pará ocupa lugar de destaque no número de casos no contexto nacional. A fim de se avaliar o perfil de citocinas e a atividade de macrófagos nas formas polares da hanseníase e correlacionar com os seus aspectos histopatológicos, foi realizado um estudo transversal com uma amostra composta por 29 pacientes portadores de uma das formas polares da hanseníase, tuberculoide ou virchowiana, dos quais foram colhidas biópsias de pele de lesões hansênicas. Pode-se observar, através da análise imonoistoquímica deste material que os grupos estudados não apresentaram diferença significativa quanto aos níveis de IL-10, TGF-β, CD68, iNOS e Lisozima. Os níveis de IL-4 não foram expressivos nos tecidos analisados e os níveis de IFN-γ foram maiores nos pacientes do grupo MHV. No polo virchowiano todas as citocinas tiveram uma tendência a uma correlação negativa com a atividade de macrófagos, no polo tuberculoide a IL-10 apresentou uma tendência à correlação negativa com os níveis de iNOS, IFN-γ e lisozima, evidenciando uma inibição da atividade macrofágica por esta citocina. Pode-se concluir que não há diferença na expressão de citocinas de perfil TH1 e TH2 nas formas polares da doença de Hansen e as citocinas apresentam uma tendência a correlação negativa com a atividade de macrófagos no pólo MHV e uma tendência a correlação positiva no pólo MHT. Novas pesquisas são necessárias para esclarecer como populações apresentam mais susceptibilidade à hanseníase que outras, um estudo semelhante com um maior número de indivíduos poderá ter resultados mais expressivos

Effectiveness Evaluation of Low-dose Spiral Computed Tomography for Lung Cancer Screening in Minhang District of Shanghai

Background and objective Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013. Methods A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases. Results The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases. Conclusion The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations

A simple but actionable metric for assessing inequity in resident greenspace exposure

An increasing number of studies aim to improve and perfect the evaluation system for assessing greenspace exposure, yet it may also become more difficult to apply the evaluation index to landscape planning. Here we propose a simple but actionable index system – Greenspace Exposure Inequity index (GEII), for assessing the inequity of residents' greenspace exposure. GEII includes quantity-based availability, distance-based accessibility, and inequity-based Gini index for assessing the difference in greenspace exposure pattern. Then we selected Shanghai as a case to test the feasibility of GEII, analyzing the spatiotemporal evolution of greenspace exposure patterns, and further demonstrating the operability of the index. (1) Availability inequity for 2012, 2015, 2018, and 2021 was 0.603, 0.512, 0.514, and 0.489. The Gini index was between 0.4 and 0.6, and presented a downward trend. (2) Accessibility inequity for 2012, 2015, 2018, and 2021 was 0.372, 0.368, 0.364, and 0.344. It can be clearly seen that it has changed less over ten years, but overall equality has been rising. (3) Using GEII to calculate the inequity of Shanghai, the Gini index for 2012, 2015, 2018, and 2021 was 0.392, 0.378, 0.373, and 0.357. The inequity of greenspace exposure assessed by GEII is gradually decreasing similarly, which illustrates the positive impact of urban greening policies. The GEII has three highlights: serviceability, human-oriented, and expandability. GEII abandons the complex computational evaluation procedures of numerous indicators and bridges the gap between theoretical research on inequity and practical planning, so GEII is of great value for alleviating the uneven exposure of residents' greenspace and scientifically optimizing landscape planning

3D cell entrapment in crosslinked thiolated gelatin-poly(ethylene glycol) diacrylate hydrogels

The combined use of natural ECM components and synthetic materials offers an attractive alternative to fabricate hydrogel-based tissue engineering scaffolds to study cell-matrix interactions in three-dimensions (3D). A facile method was developed to modify gelatin with cysteine via a bifunctional PEG linker, thus introducing free thiol groups to gelatin chains. A covalently crosslinked gelatin hydrogel was fabricated using thiolated gelatin and poly(ethylene glycol) diacrylate (PEGdA) via thiol-ene reaction. Unmodified gelatin was physically incorporated in a PEGdA-only matrix for comparison. We sought to understand the effect of crosslinking modality on hydrogel physicochemical properties and the impact on 3D cell entrapment. Compared to physically incorporated gelatin hydrogels, covalently crosslinked gelatin hydrogels displayed higher maximum weight swelling ratio (Q max), higher water content, significantly lower cumulative gelatin dissolution up to 7 days, and lower gel stiffness. Furthermore, fibroblasts encapsulated within covalently crosslinked gelatin hydrogels showed extensive cytoplasmic spreading and the formation of cellular networks over 28 days. In contrast, fibroblasts encapsulated in the physically incorporated gelatin hydrogels remained spheroidal. Hence, crosslinking ECM protein with synthetic matrix creates a stable scaffold with tunable mechanical properties and with long-term cell anchorage points, thus supporting cell attachment and growth in the 3D environment. © 2011.Link_to_subscribed_fulltex