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1.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256015

RESUMO

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.


Assuntos
Cimenos , Óleos Voláteis , Origanum , Animais , Ratos , Óleos Voláteis/farmacologia , Timol/farmacologia , Rim , Inflamação/tratamento farmacológico , Arginina/farmacologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38079620

RESUMO

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

3.
Mar Pollut Bull ; 197: 115708, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951123

RESUMO

Seagrass ecosystems are important organic carbon (Corg) sinks with great potential to contribute to climate change mitigation strategies. However, the high spatial and temporal variability is a barrier to the accurate assessment of national Corg stocks. This study provides a national assessment of Corg within seagrass meadows, including spatial and temporal variations. The highest Corg stocks were within mangrove-associated (44.3 ± 8.27 Mg ha-1), while near-surface sediments were highest in reef-associated meadows (10.20 ± 3.69 Mg ha-1). Regionally, the highest stocks were in the Upper Andaman coast in monospecific meadows (51.7 ± 7.14 Mg ha-1). Corg stocks in near-surface sediments were significantly different across historical trends (p < 0.001), with the highest stocks in stable meadows (9.28 ± 3.39 Mg ha-1). The national Corg stock within seagrass meadows sediment was 40.45 ± 11.59 Mg C ha-1. The results of this study highlighted the complexity of blue carbon in seagrass meadows and the associated impacts on national Corg assessments, carbon accounting, and conservation strategies.


Assuntos
Carbono , Ecossistema , Carbono/análise , Tailândia , Sedimentos Geológicos , Sequestro de Carbono
4.
Sci Total Environ ; 904: 166618, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37643707

RESUMO

Coastal blue carbon ecosystems can be an important nature-based solution for mitigating climate change, when emphasis is given to their protection, management, and restoration. Globally, there has been a rapid increase in blue carbon research in the last few decades, with substantial investments on national scales by the European Union, the USA, Australia, Seychelles, and Belize. Blue carbon ecosystems in South and Southeast Asia are globally diverse, highly productive and could represent a global hotspot for carbon sequestration and storage. To guide future efforts, we conducted a systematic review of the available literature on two primary blue carbon ecosystems-seagrasses and mangroves-across 13 countries in South and Southeast Asia to assess existing national inventories, review current research trends and methodologies, and identify existing knowledge gaps. Information related to various aspects of seagrass and mangrove ecosystems was extracted from 432 research articles from 1967 to 2022. We find that: (1) blue carbon estimates in several countries have limited data, especially for seagrass meadows compared to mangrove ecosystems, although the highest reported carbon stocks were in Indonesia and the Philippines with 4,515 and 707 Tg within mangrove forest and 60.9 and 63.3 Tg within seagrass meadows, respectively; (2) there is a high difference in the quantity and quality of data between mangrove and seagrass ecosystems, and the methodologies used for blue carbon estimates are highly variable across countries; and (3) most studies on blue carbon stocks are spatially biased towards more familiar study areas of individual countries, than several lesser-known suspected blue carbon hotspots. In sum, our review demonstrates the paucity and variability in current research in the region, and highlights research frontiers that should be addressed by future research before the robust implementation of these ecosystems into national climate strategies.


Assuntos
Carbono , Ecossistema , Sudeste Asiático , Áreas Alagadas , Indonésia , Sequestro de Carbono
5.
Hydrobiologia ; : 1-15, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37363743

RESUMO

We investigated the influences of oceanographic variables on recruitment patterns of the acorn barnacle Chthamalus malayensis and the rock oyster Saccostrea cuccullata, key space occupiers on tropical intertidal rocky shores. Recruitment data and nearshore environmental variables were obtained at spatial (regional and local) and temporal (monthly) scales on the west coast of Thailand. The relationship between the recruitment of each species and combinations of environmental variables was modeled. The climate of the study sites is influenced by the southwest and northeast monsoons of the Indochinese monsoon system. Observations showed that recruitment of both species and oceanographic variables exhibited differences at either local scale or monthly scale or both. Recruitment of both species was positively related to temperature, while barnacle recruitment was negatively related to salinity, but oyster recruitment was positively related to salinity. Barnacles showed a greater rate of recruitment when south-westerly onshore winds predominated during the southwest monsoon season, while the influence of wind patterns on rock oyster recruitment was not clear. Differential larval delivery regulated by monsoon-driven currents is, therefore, a potential determinant of barnacle recruitment. Our study highlights the roles of monsoon-influenced oceanographic processes as predictors of recruitment patterns of intertidal species in a tropical system. Supplementary Information: The online version contains supplementary material available at 10.1007/s10750-023-05256-w.

6.
Medicina (Kaunas) ; 59(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36837419

RESUMO

Background and Objectives: The saphenous vein is one of the most common used grafts (SVG) for surgical revascularization. The mechanism of the SVGs occlusion is still unknown. Surgical preparation techniques have an important role in the early and late graft occlusion. Our study analyzed the influence of the three different surgical techniques on the histological and immunohistochemical characteristics of the vein grafts. Methods: Between June 2019 and December 2020, 83 patients who underwent surgical revascularization were prospectively randomly assigned to one of the three groups, according to saphenous vein graft harvesting (conventional (CVH), no-touch (NT) and endoscopic (EVH)) technique. The vein graft samples were sent on the histological (hematoxylin-eosin staining) and immunohistochemical (CD31, Factor VIII, Caveolin and eNOS) examinations. Results: The CVH, NT, and EVH groups included 27 patients (mean age 67.66 ± 5.6), 31 patients (mean age 66.5 ± 7.4) and 25 patients (mean age 66 ± 5.5), respectively. Hematoxylin-eosin staining revealed a lower grade of microstructural vein damage in the NT group (2, IQR 1-2) in comparison with CVH and EVH (3, IQR 2-4), (4, IQR 2-4) respectively (p < 0.001). Immunohistochemical examination revealed a high grade of staining in the NT group compared to the CVH and EVH group (CD 31 antibody p = 0.02, FVIII, p < 0.001, Caveolin, p = 0.001, and eNOS, p = 0.003). Conclusion: The best preservation of the structural vein integrity was in the NT group, while the lowest rate of leg wound complication was in the EVH group. These facts increase the interest in developing and implementing the endoscopic no-touch technique.


Assuntos
Ponte de Artéria Coronária , Veia Safena , Idoso , Humanos , Pessoa de Meia-Idade , Caveolinas/análise , Ponte de Artéria Coronária/métodos , Endoscopia , Veia Safena/química , Veia Safena/patologia , Veia Safena/transplante , Grau de Desobstrução Vascular
7.
J Ethnopharmacol ; 301: 115779, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36202166

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Helichrysum italicum has been widely used in traditional medicine to treat allergies, colds, cough, skin, liver and gallbladder disorders, inflammation, infections, and sleeplessness. Furthermore, it possesses considerable wound healing and skin protective properties, documented by several in vivo studies performed on animals. However, there is a lack of experimental evidence supporting its potential as a topical agent tested by human clinical trials. AIM OF THE STUDY: The study aimed to investigate the skin protective activity of cotton gauze and polypropylene non-woven fabric, impregnated with H. italicum extract by the integrated supercritical CO2 extraction-supercritical solvent impregnation process. MATERIALS AND METHODS: The integrated process of supercritical CO2 extraction of H. italicum and the impregnation of cotton gauze and polypropylene non-woven fabric was performed under 350 bar and 40 °C with and without the addition of ethanol as a cosolvent. Impregnated textile materials were tested in vivo for their bioactivity on irritated human skin. Randomized in vivo studies performed involved assays of both safety and efficacy of the impregnated textiles. The effects were evaluated using the in vivo non-invasive biophysical measurements of the following skin parameters: electrical capacitance, transepidermal water loss, melanin index, erythema index, and skin pH. RESULTS: Both cotton gauze and polypropylene non-woven fabric were impregnated with H. italicum extracts under supercritical conditions with considerable values of the impregnation yield (1.97%-4.25%). The addition of ethanol as a cosolvent during the process caused significant changes in the incorporated extracts' impregnation yield and chemical profile. Both impregnated textile materials were safe, evaluated by their testing on the human skin with no cause of any irritation and redness. However, efficacy studies revealed that polypropylene non-woven fabric impregnated with H. italicum extract with ethanol as a cosolvent, possessed significantly greater potential for skin protection than the other investigated samples. CONCLUSIONS: The present study demonstrated the feasibility of the combined supercritical extraction and impregnation process in developing materials for topical application based on H. italicum extract. The results of in vivo studies performed on human volunteers confirmed the suitability of H. italicum active components to be a part of human skin protective preparations because of their ability to maintain the skin unimpaired. Traditionally claimed applications as a medicinal plant capable of regenerating skin have been scientifically proven, in addition to employing green technology in obtaining the impregnated materials with a broad spectrum of utilization.


Assuntos
Helichrysum , Animais , Humanos , Helichrysum/química , Dióxido de Carbono , Polipropilenos , Extratos Vegetais/uso terapêutico , Etanol
8.
Pharmaceutics ; 13(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34834334

RESUMO

Immortelle, as rich source of chlorogenic acid and the phloroglucinol alpha-pyrone compound arzanol, possesses anti-inflammatory and antioxidant properties, affects cell regeneration, and has positive effect on many skin conditions. Hemp oil, characterized by a favorable omega-6 to omega-3 ratio, as well as an abundance of essential fatty acids and vitamin E, participates in immunoregulation and also act as an anti-inflammatory. In the present study, we examined the effect on the skin of creams and emulgels with immortelle extract and hemp oil, by comparing them to placebo samples and a non-treated control. A long-term in vivo study of biophysical skin characteristics, which lasted for 30 days, was conducted on 25 healthy human volunteers. Measured parameters were electrical capacitance of the stratum corneum, trans-epidermal water loss (TEWL), and skin pH and erythema index. Further, a sensory study was carried out in which the panelists had to choose descriptive terms for sensory attributes in questionnaire. The results showed that application of all preparations led to increase of skin hydration and TEWL reduction, while the skin was not irritated, and its normal pH was not disrupted. This study also showed importance of the carrier. Not only were emulgels described by panelists as preparations with better sensory properties, there was a significant difference between the skin hydration effect of emulgel with immortelle extract and hemp oil compared to the placebo emulgel, which was not the case with creams. Such findings indicated enhanced delivery of herbal active substances from emulgel compared to the cream.

9.
Sci Total Environ ; 783: 146858, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34088119

RESUMO

Seagrasses have the ability to contribute towards climate change mitigation, through large organic carbon (Corg) sinks within their ecosystems. Although the importance of blue carbon within these ecosystems has been addressed in some countries of Southeast Asia, the regional and national inventories with the application of nature-based solutions are lacking. In this study, we aim to estimate national coastal blue carbon stocks in the seagrass ecosystems in the countries of Southeast Asia including the Andaman and Nicobar Islands of India. This study further assesses the potential of conservation and restoration practices and highlights the seagrass meadows as nature-based solution for climate change mitigation. The average value of the total carbon storage within seagrass meadows of this region is 121.95 ± 76.11 Mg ha-1 (average ± SD) and the total Corg stock of the seagrass meadows of this region was 429.11 ± 111.88 Tg, with the highest Corg stock in the Philippines (78%). The seagrass meadows of this region have the capacity to accumulate 5.85-6.80 Tg C year-1, which accounts for $214.6-249.4 million USD. Under the current rate of decline of 2.82%, the seagrass meadows are emitting 1.65-2.08 Tg of CO2 year-1 and the economic value of these losses accounts for $21.42-24.96 million USD. The potential of the seagrass meadows to the offset current CO2 emissions varies across the region, with the highest contribution to offset is in the seagrass meadows of the Philippines (11.71%). Current national policies and commitments of nationally determined contributions do not include blue carbon ecosystems as climate mitigation measures, even though these ecosystems can contribute up to 7.03% of the countries' reduction goal of CO2 emissions by 2030. The results of this study highlight and promote the potential of the southeast Asian seagrass meadows to national and international agencies as a practical scheme for nature-based solutions for climate change mitigation.


Assuntos
Mudança Climática , Ecossistema , Sudeste Asiático , Carbono/análise , Sequestro de Carbono , Sedimentos Geológicos , Índia , Filipinas
10.
Mar Pollut Bull ; 163: 111913, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33373889

RESUMO

Although seagrass ecosystems provide various ecosystem services, the implications in correspondence with temporal changes of the meadows is lacking. In this study, we analyzed two-decade changes of the seagrass area with the organic carbon storage and the sources at Libong island in Thailand. The seagrass area covered 841 ha in 2019, after two decades of decline (3.2 and 0.6% yr-1 between 2004 and 2009 and 2009-2019, respectively). Although δ13C was not significant between depth layers (p > 0.05), the general trend suggested that the terrestrial source of carbon is dominating bottom depth layer (31.7-37.2%), mixture of terrestrial (19.7-30.3%), seagrass (22.9-29.6%), mangrove (16.8-43.0%) and CPOM (11.2-25.4%) in the middle, and mangroves and seagrasses are dominating surface layer (28.3-66.2 and 29.3-36.5%, respectively). These trends approximately correspond to the areal changes of the meadows, as well as changes of urban area and water quality, providing detailed information on the meadow changes and possible causes.


Assuntos
Carbono , Ecossistema , Carbono/análise , Sequestro de Carbono , Sedimentos Geológicos , Tailândia
11.
Mol Syndromol ; 11(2): 104-109, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32655342

RESUMO

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been linked to malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. RYR1 is an intracellular calcium release channel and plays a crucial role in the sarcoplasmic reticulum and transverse tubule connection. Here, we report 2 fetuses from the same parents with compound heterozygous mutations in the RYR1 gene (c.10347+1G>A and c.10456-2Α>G) who presented with fetal akinesia and polyhydramnios at 27 and 19 weeks of gestation with intrauterine growth restriction in the third pregnancy. The prospective parents of the fetuses were heterozygous carriers for c.10456-2Α>G (mother) and c.10347+1G>A (father). Both mutations affect splice sites resulting in dysfunctional protein forms probably missing crucial domains of the C-terminus. Our findings reveal a new RYR1 splice site mutation (c.10456-2Α>G) that may be associated with the clinical features of myopathies, expanding the RYR1 spectrum related to these pathologies.

12.
Dermatol Ther ; 33(4): e13511, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32372458

RESUMO

The use of donkey milk has a long history in external dermal application for cosmetic and medical purposes. The encapsulation of different drugs into nanoliposomes and nutrients may have many benefits for the delivery of the targeted substance. The aim of the present study is to test creams with nanoliposomes encapsulated with skimmed donkey milk, reported in our registered patent, compared with effect of the placebo cream and the untreated skin. To investigate the effect of formulated cream, we have measured the electrical capacitance, transepidermal water loss and the skin pH value. The study included 15 healthy volunteers (11 women and 4 men). The patented creams exhibited satisfactory moisturizing properties very soon after application, while hydration was reached earlier in the spots treated with night cream. Transepidermal water loss slightly decreased only after 4 weeks of treatment in each of the spots assessed. The pH value was similar after each of the treatments. Tested creams may enhance the moisture of skin very soon after application, in this way potentially enable deeper permeation of phospholipids and essential proteins, without changing the pH. It may also contribute to additional anti-aging effects.


Assuntos
Cosméticos , Equidae , Animais , Feminino , Humanos , Masculino , Leite , Pele , Creme para a Pele , Fenômenos Fisiológicos da Pele
13.
Int J Cosmet Sci ; 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29723433

RESUMO

OBJECTIVE: The aim of this study was in vitro and in vivo characterization of cosmetic cream with 6% of wild apple fruit water extract, containing 3.5% of alpha-hydroxyacids-AHAs and polyphenolic compounds, stabilized by biodegradable alkyl-polyglucoside emulsifiers. METHODS: In vitro characterization of cream included organoleptic and physico-chemical (pH values and electrical conductivity) analysis, antioxidant activity-AA estimation (using DPPH test) during 180 days of storage at 22±2°C and determination of cosmetic active substances content-AHAs (using HPLC analysis). In vivo estimation of skin irritation potential after creams application under occlusion during 24h was investigated employing the biophysical methods on 12 healthy volunteers; hydration efficiency, transepidermal water loss-TEWL, skin pH, erythema-EI and melanin index-MI on 10 healthy volunteers after 28 days of cream application and bleaching efficiency on 10 healthy volunteers after 7 days of cream application after artificially induced skin hyperpigmentation. RESULTS: Investigated cosmetic cream was pale beige color, odorless, semi-solid consistency and homogeneous, with pH values of 6.53±0.14, electrical conductivity above 50 µS/cm and AA of 24.96%RSC after preparation and these characteristics were stable during investigated period. In vivo measurements revealed absence of skin irritation after cream application under occlusion, which was part of it's safety profile. Increase of skin hydration after 14 days of cream application was 17.28±12.23 and after 28 days 21.19±7.59. In addition, in performed experiment TEWL and skin pH values during cream application remained unchanged. Cream application after artificial hyperpigmentation induced decrease of MI (∆MI after 7 days was -45.30±18.55) CONCLUSION: Formulated cosmetic cream with 6% of standardized wild apple fruit water extract and stabilized by biodegradable alkyl-polyglucoside emulsifiers demonstrated good stability, acceptable level of in vitro antioxidant activity, absence of skin irritation after cream application under occlusion and positive effects of cream on human skin after application (hydrating and bleaching effects). All mentioned properties make the cream suitable for possible usage as cosmetic product for preventing the skin damages caused by oxidative stress, for moisturizing the dry skin and bleaching of skin hyperpigmentation. This article is protected by copyright. All rights reserved.

14.
Acta Neurol Belg ; 118(3): 423-427, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29594965

RESUMO

It is believed that myasthenia gravis (MG) with antibodies to muscle-specific tyrosine kinase (MuSK) is the most severe form of the disease, especially in the first years of the disease. The aim of our study was to investigate quality of life (QoL) in a population of patients with MuSK MG compared to those with MG who have antibodies to acetylcholine receptor (AChR) in their sera. The study group consisted of 35 MuSK MG patients (28 females and 7 males), while the control group included 38 AChR MG patients matched for gender, age, and duration of the disease. SF-36 questionnaire was used to evaluate the health-related QoL. Following scales were also used: Hamilton's scales for depression and anxiety, the Multidimensional Scale of Perceived Social Support, and the Acceptance of Illness Scale. Physical domain scores of QoL were similarly affected in both MuSK and AChR groups, while mental domain and total SF-36 scores were even better in MuSK MG patients. Social support was better in the MuSK group (77.3 ± 9.3 vs. 70.6 ± 14.1, p < 0.05). SF-36 total score correlated with depression (rho = 0.54, p < 0.01), anxiety (rho = 0.49, p < 0.01), and MSPSS (rho = - 0.35, p < 0.05), and depression was an independent predictor of worse QoL. Besides therapy of weakness, psychiatric treatment and different forms of psychosocial condition should be part of regular therapeutic protocols for MG. Adequate team work of health professionals and family can provide a healthy mental environment in which a MuSK MG patient would feel more comfortable in spite of the disease.


Assuntos
Autoanticorpos/imunologia , Miastenia Gravis/terapia , Qualidade de Vida , Receptores Proteína Tirosina Quinases/metabolismo , Meio Ambiente , Feminino , Humanos , Masculino , Miastenia Gravis/psicologia , Resultado do Tratamento , Tirosina/metabolismo
15.
Drug Discov Today ; 20(7): 812-23, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25660507

RESUMO

Over the past few decades hot melt extrusion (HME) has emerged as a powerful processing technology for the production of pharmaceutical solid dosage forms in which an active pharmaceutical ingredient (API) is dispersed into polymer matrices. It has been shown that formulations using HME can provide time-controlled, sustained and targeted drug delivery, and improved bioavailability of poorly soluble drugs. In this review, the basic principles of the HME process are described together with an overview of some of the most common biodegradable and nonbiodegradable polymers used for the preparation of different formulations using this method. Further, the applications of HME in drug delivery and analytical techniques employed to characterize HME products are addressed.


Assuntos
Portadores de Fármacos , Temperatura Alta , Preparações Farmacêuticas/química , Polímeros/química , Tecnologia Farmacêutica/métodos , Animais , Disponibilidade Biológica , Química Farmacêutica , Preparações de Ação Retardada , Vias de Administração de Medicamentos , Humanos , Preparações Farmacêuticas/administração & dosagem , Solubilidade
16.
Int J Pharm ; 480(1-2): 73-83, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25575472

RESUMO

In this study, water-swellable multiblock copolymers composed of semi-crystalline poly(ϵ-caprolactone) [PCL] blocks and amorphous blocks consisting of poly(D,L-lactide) (PDLLA) and poly(ethylene glycol) (PEG) [PDLLA-PEG] were synthesized. The block ratio of these [PDLLA-PEG]-b-[PCL] multiblock copolymers was varied and the degradation of implants prepared of these polymers by hot melt extrusion (HME) was compared with implants prepared of [PCL-PEG]-b-[PCL], a copolymer which has been described previously (Stankovic et al., 2014). It was shown that the initial degradation rate of the [PDLLA-PEG]-b-[PCL] multiblock copolymers increased with increasing the content of amorphous [PDLLA-PEG] block and that the degradation rate of these multiblock copolymers was faster than that of the [PCL-PEG]-b-[PCL] multiblock copolymers due to rapid degradation of the [PDLLA-PEG] block. Furthermore, the release of the model proteins lysozyme and bovine serum albumin from polymer implants prepared by HME was studied. It was found that the protein release from [PDLLA-PEG]-b-[PCL] copolymers was incomplete, which is not acceptable for any application of these polymers. Besides, [PCL-PEG]-b-[PCL] copolymers showed slow and continuous release. We hypothesize that the incomplete release is explained by an irreversible interaction between the proteins and polymer degradation products or by entrapment of the protein in the hydrophobic and non-swellable polymer matrix that was left after degradation and loss of the hydrophilic [PDLLA-PEG] blocks from the degrading polymer.


Assuntos
Poliésteres/química , Polietilenoglicóis/química , Proteínas/administração & dosagem , Química Farmacêutica/métodos , Cristalização , Preparações de Ação Retardada , Implantes de Medicamento , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Muramidase/administração & dosagem , Muramidase/química , Proteínas/química , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/química , Água/química
17.
Eur J Pharm Biopharm ; 87(2): 329-37, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24602675

RESUMO

In this study, the in vitro release of proteins from novel, biodegradable phase-separated poly(ε-caprolactone-PEG)-block-poly(ε-caprolactone), [PCL-PEG]-b-[PCL]) multiblock copolymers with different block ratios and with a low melting temperature (49-55°C) was studied. The effect of block ratio and PEG content of the polymers (i.e. 22.5, 37.5 and 52.5 wt%) as well as the effect of protein molecular weight (1.2, 5.8, 14, 29 and 66 kDa being goserelin, insulin, lysozyme, carbonic anhydrase and albumin, respectively) on protein release was investigated. Proteins were spray-dried with inulin as stabilizer to obtain a powder of uniform particle size. Spray-dried inulin-stabilized proteins were incorporated into polymeric implants by hot melt extrusion. All incorporated proteins fully preserved their structural integrity as determined after extraction of these proteins from the polymeric implants. In general, it was found that the release rate of the protein increased with decreasing molecular weight of the protein and with increasing the PEG content of the polymer. Swelling and degradation rate of the copolymer increased with increasing PEG content. Hence, release of proteins of various molecular weights from [PCL-PEG]-b-[PCL] multi-block copolymers can be tailored by varying the PEG content of the polymer.


Assuntos
Implantes Absorvíveis , Portadores de Fármacos , Poliésteres/química , Polietilenoglicóis/química , Proteínas/química , Química Farmacêutica , Implantes de Medicamento , Cinética , Peso Molecular , Estabilidade Proteica , Solubilidade , Tecnologia Farmacêutica/métodos , Temperatura de Transição
18.
Eur J Pharm Sci ; 49(4): 578-87, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23707467

RESUMO

Parenteral protein delivery requires preservation of the integrity of proteins and control over the release kinetics. In order to preserve the integrity, parenteral protein delivery formulations typically need to be processed at low temperatures. Therefore, we synthesized a novel low melting biodegradable hydrophilic multiblock copolymer composed of poly (ethylene glycol) and poly (ε-caprolactone) to allow extrusion at relatively low temperatures. We investigated the extrusion characteristics of this polymer and explored a strategy how to control the release of the model protein lysozyme from small diameter extruded implants. It was found that the polymer could be well extruded at temperatures as low as 55 °C. Moreover, lysozyme remained active both during extrusion as well as during release. Lysozyme release kinetics could be tailored by the co-incorporation of an oligosaccharide, inulin, which functions as a pore-forming excipient. It was concluded that this hydrophilic multiblock copolymer has promising characteristics for the preparation by melt extrusion of protein delivery implants with a release profile that is sustained over a period of more than 7 months.


Assuntos
Sistemas de Liberação de Medicamentos , Implantes de Medicamento , Muramidase/química , Poliésteres/química , Polietilenoglicóis/química , Interações Hidrofóbicas e Hidrofílicas , Inulina/química , Micrococcus/efeitos dos fármacos , Muramidase/administração & dosagem , Proteínas , Temperatura
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