scholarly journals Tween® Preserves Enzyme Activity and Stability in PLGA Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2946
Author(s):  
Jason Thomas Duskey ◽  
Ilaria Ottonelli ◽  
Arianna Rinaldi ◽  
Irene Parmeggiani ◽  
Barbara Zambelli ◽  
...  

Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs.

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 990-996 ◽  
Author(s):  
Jan Sjöberg ◽  
Cat Halthur ◽  
Sigurdur Y. Kristinsson ◽  
Ola Landgren ◽  
Ulla Axdorph Nygell ◽  
...  

Abstract In recent decades, attention has focused on reducing long-term, treatment-related morbidity and mortality in Hodgkin lymphoma (HL). In the present study, we looked for trends in relative survival for all patients diagnosed with HL in Sweden from 1973-2009 (N = 6949; 3985 men and 2964 women; median age, 45 years) and followed up for death until the end of 2010. Patients were categorized into 6 age groups and 5 calendar periods (1973-1979, 1980-1986, 1987-1994, 1994-2000, and 2001-2009). Relative survival improved in all age groups, with the greatest improvement in patients 51-65 years of age (P < .0005). A plateau in relative survival was observed in patients below 65 years of age during the last calendar period, suggesting a reduced long-term, treatment-related mortality. The 10-year relative survival for patients diagnosed in 2000-2009 was 0.95, 0.96, 0.93, 0.80, and 0.44 for the age groups 0-18, 19-35, 36-50, 51-65, and 66-80, respectively. Therefore, despite progress, age at diagnosis remains an important prognostic factor (P < .0005). Advances in therapy for patients with limited and advanced-stage HL have contributed to an increasing cure rate. In addition, our findings support that long-term mortality of HL therapy has decreased. Elderly HL patients still do poorly, and targeted treatment options associated with fewer side effects will advance the clinical HL field.


1981 ◽  
Vol 60 (5) ◽  
pp. 491-498 ◽  
Author(s):  
F. Boomsma ◽  
J. H. B. de Bruyn ◽  
F. H. M. Derkx ◽  
M. A. D. H. Schalekamp

1. The relationship between the antihypertensive action of captopril and its inhibitory effect on angiotensin I(ANG I)-converting enzyme has been investigated. Converting enzyme was measured in plasma by its ability to generate hippuric acid from the synthetic substrate hippuryl-l-histidyl-l-leucine. Inhibition by captopril appeared transient on storage of the plasma samples at −20°C, so that measurements in such samples were not a valid index of the effect in vivo. 2. Rapid reversal of captopril's inhibitory effect on ANG I-converting enzyme in plasma was achieved by the addition of N-ethylmaleimide (0.1 mmol/l). In this way an estimate of converting enzyme ‘concentration’ was obtained both in stored and in freshly prepared plasma samples. Measurements of converting enzyme ‘activity’ in freshly prepared samples, in the absence of N-ethylmaleimide, were used as an index of inhibition in vivo. 3. In eight hypertensive subjects ANG I-converting enzyme ‘concentration’ did not change after a single oral 100 mg dose of captopril. Long-term treatment of 10 hypertensive subjects with captopril was associated with a gradual increase in converting enzyme ‘concentration’ from 29 ± 2 to 47 ± 3 m-units/ml (mean ± sem) over a period of several weeks. In contrast, captopril caused a rapid fall of converting enzyme ‘activity’. 4. Abrupt withdrawal of captopril after long-term treatment caused a gradual decrease in ANG I-converting enzyme ‘concentration’ to the control value. In contrast, converting enzyme ‘activity’ rose rapidly and became equal to enzyme ‘concentration’ 2 days after the drug had been stopped. 5. The concentration of enzymatically active renin in plasma rose from 13 ± 3 to 81 ± 34 μ-units/ml during long-term captopril treatment (mean ± sem). Blood pressure fell from 168 ±4/108 ± 3 to 140 ± 3/90 ± 3 mmHg and had not returned to the control value in the first week after the drug had been stopped, despite the fact that circulating active renin and ANG I-converting enzyme ‘activity’ were elevated. 6. It is concluded that long-term inhibition of ANG I-converting enzyme by captopril is associated with an increased plasma concentration of this enzyme. The results also suggest that the level of converting enzyme ‘activity’ in plasma is not the only factor that determines the long-term effect of captopril on blood pressure.


2020 ◽  
Vol 25 (4) ◽  
pp. 60-62
Author(s):  
Corina Adelina Zah ◽  
Andreea Emiliana Toporău ◽  
Paul Grama

Abstract Atopic dermatitis (AD) is a chronic inflammatory disease characterized by skin dryness, pruritus and eczematous lesions with various periods of relapse. Symptomatology can appear in childhood and can persist in adulthood. Chronic treatment is required with corticosteroids being the standard options. The side effects of this type of long-term treatment represent a major concern for the pediatric patients. This review aims to give an update of the options used for treatment, apart from the systemic corticosteroids. Mild-to-moderate AD had a good response to creams containing fig and oatmeal extracts and inhibitors of phosphodiesterase-4 (crisaborole). In cases of severe AD, future treatment options could include monoclonal antibodies such as omalizumab and dupilumab


Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2149
Author(s):  
Juan L. Paris ◽  
Paz de la Torre ◽  
Ana I. Flores

Allergy constitutes a major health issue due to its large prevalence. The established therapeutic approaches (allergen avoidance, antihistamines, and corticosteroids) do not address the underlying causes of the pathology, highlighting the need for other long-term treatment options. Antigen-specific immunotherapy enables the long-term control of allergic diseases by promoting immunological tolerance to the allergen. However, efficacious immunotherapies are not available for all possible allergens, and the risk of undesired reactions during therapy remains a concern, especially in patients with severe allergic reactions. In this context, two types of therapeutic strategies appear especially promising for the future in the context of allergy: cell therapy and bio- or nano-material-based therapy. In this review, the main strategies developed this far in these two types of strategies are discussed, with several examples illustrating the different approaches.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Cheng Ma ◽  
Xin Wu ◽  
Xiaotian Shen ◽  
Yanbo Yang ◽  
Zhouqing Chen ◽  
...  

Abstract Traumatic brain injury (TBI) is exceptionally prevalent in society and often imposes a massive burden on patients’ families and poor prognosis. The evidence reviewed here suggests that gender can influence clinical outcomes of TBI in many aspects, ranges from patients’ mortality and short-term outcome to their long-term outcome, as well as the incidence of cognitive impairment. We mainly focused on the causes and mechanisms underlying the differences between male and female after TBI, from both biological and sociological views. As it turns out that multiple factors contribute to the gender differences after TBI, not merely the perspective of gender and sex hormones. Centered on this, we discussed how female steroid hormones exert neuroprotective effects through the anti-inflammatory and antioxidant mechanism, along with the cognitive impairment and the social integration problems it caused. As to the treatment, both instant and long-term treatment of TBI requires adjustments according to gender. A further study with more focus on this topic is therefore suggested to provide better treatment options for these patients.


2019 ◽  
Vol 8 ◽  
pp. 216495611985803 ◽  
Author(s):  
Deanna R Befus ◽  
Sharon Hull ◽  
Justine Strand de Oliveira ◽  
Gillian Sanders Schmidler ◽  
Morris Weinberger ◽  
...  

Background Migraine is a disabling neurological disorder and the sixth biggest cause of disability worldwide. The World Health Organization has declared migraine a major public health problem due to a paucity of knowledge about cause and effective treatment options. Both in incidence and severity, migraine disproportionately affects people occupying marginalized social locations (SL). Managed pharmacologically, migraine is treated with daily preventive and as-needed abortive medications. Both come with high literal and figurative costs: intolerable side effects, medication interactions, and prohibitive prices. Cost prohibitive, ineffective, and unsustainable pharmacological treatment options have contributed to high levels of interest in complementary approaches by people with migraine, but little is known about their motivations, patterns of use or access, or how these may vary by SL. Method We conducted focus groups with 30 people with migraine to explore their desires and recommendations for migraine clinicians and researchers. We used qualitative content analysis to identify themes. Outcomes: We identified 4 themes: a more holistic, collaborative, long-term treatment approach; medication as a short-term solution; high personal and economic costs of medication; and desire for more information and access to natural approaches. Across SL, participants expressed keen interest in integrative approaches and wanted better access to complementary modalities. Participants in marginalized SL described reliance on traditional/folk remedies, including engagement with family and community healers, who they described as more affordable and culturally accessible. Conclusions Holistic and integrative approaches were preferred over medication as long-term migraine management strategies. However, people in marginalized SL, while disproportionately disabled by migraine, did not feel as comfortable accessing integrative approaches through currently available channels. Engaging with these communities and using a critical lens to explore barriers to access can develop options to make complementary modalities more approachable, while also attending to systemic blind spots that may unintentionally alienate socially marginalized groups.


Author(s):  
Felix Schoenrath ◽  
Jan Klages ◽  
Volkmar Falk

Cardiac surgery in heart failure (HF) patients is gaining more and more importance as HF prevalence is increasing in the general population. Therefore, surgery offers potential benefits at any stage of HF prognosis and for various HF aetiologies. Since both decision making and treatment options are becoming increasingly complex in our aging population, decisions should be made based on a specialized HF team, to achieve optimal and sustained results for the patient. Currently, most intermediate and long-term treatment options for end stage HF patients result in surgical interventions (LVAD therapy, transplantation). However, both pre- and post-operative as well as outpatient care is often managed by the cardiologist. Therefore, gaining expertise in the field through indications and complication management, as well as the know-how surrounding surgical principles is highly valuable for every cardiologist.


2013 ◽  
Vol 33 (03) ◽  
pp. 218-224 ◽  
Author(s):  
M. Brodmann

SummaryThe focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve.The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment.At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor.


Sign in / Sign up

Export Citation Format

Share Document