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1.
Physiother Res Int ; 29(3): e2109, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961771

ABSTRACT

INTRODUCTION: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High-definition transcranial direct current stimulation (HD-tDCS) has been tested in patients with COVID-19; however, previous studies did not investigate the HD-tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID. CASE PRESENTATION: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD-tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention. IMPLICATIONS ON PHYSIOTHERAPY PRACTICE: HD-tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID.


Subject(s)
Breathing Exercises , COVID-19 , Post-Acute COVID-19 Syndrome , Respiratory Muscles , Transcranial Direct Current Stimulation , Humans , Female , Male , Middle Aged , Aged , Adult , Respiratory Muscles/physiopathology , SARS-CoV-2 , Treatment Outcome , Muscle Strength/physiology , Respiratory Function Tests
2.
Int J Biol Macromol ; 270(Pt 1): 132062, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705340

ABSTRACT

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model. The swelling ratio of the beads indicated pH-responsiveness, with maximum water absorption at pH 6.8, and strong mucoadhesion, increasing primarily with higher polymer concentrations. The beads exhibited thermal stability and no chemical interaction with IND, showing improved mechanical properties. Furthermore, the beads remained stable during accelerated and long-term storage studies. The beads were found to be biocompatible, and IND encapsulation improved cell viability (>70 % in both models, 79 % in VN) and modified IND permeation through the models (6.3 % for F5 formulation (κ-Car 0.90 % w/v | Ser 1.2 % w/v| IND 3.0 g); 10.9 % for free IND, p < 0.05). Accordingly, κ-Car/Ser/IND beads were demonstrated to be a promising IND drug carrier to improve oral administration while mitigating the side effects of non-steroidal anti-inflammatories.


Subject(s)
Carrageenan , Delayed-Action Preparations , Indomethacin , Sericins , Indomethacin/chemistry , Indomethacin/administration & dosage , Indomethacin/pharmacokinetics , Carrageenan/chemistry , Administration, Oral , Humans , Sericins/chemistry , Delayed-Action Preparations/chemistry , Drug Carriers/chemistry , Drug Liberation , Cell Survival/drug effects , Microspheres , Animals , Caco-2 Cells , Hydrogen-Ion Concentration
3.
Article in English | MEDLINE | ID: mdl-38691149

ABSTRACT

RATIONALE: Therapeutic approaches to mitigating traumatic memories have often faced resistance. Exploring safe reconsolidation blockers, drugs capable of reducing the emotional valence of the memory upon brief retrieval and reactivation, emerges as a promising pharmacological strategy. Towards this objective, preclinical investigations should focus on aversive memories resulting in maladaptive outcomes and consider sex-related differences to enhance their translatability. OBJECTIVES: After selecting a relatively high training magnitude leading to the formation of a more intense and generalized fear memory in adult female and male rats, we investigated whether two clinically approved drugs disrupting its reconsolidation remain effective. RESULTS: We found resistant reconsolidation impairment by the α2-adrenergic receptor agonist clonidine or cannabidiol, a major non-psychotomimetic Cannabis sativa component. However, pre-retrieval administration of D-cycloserine, a partial agonist at the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor complex, facilitated their impairing effects on reconsolidation. A similar reconsolidation blockade by clonidine or cannabidiol was achieved following exposure to a non-conditioned but generalized context after D-cycloserine administration. This suggests that sufficient memory destabilization can accompany generalized fear expression. Combining clonidine with cannabidiol without potentiating memory destabilization by D-cycloserine was ineffective. CONCLUSIONS: These findings highlight the importance of NMDA receptor signaling in memory destabilization and underscore the efficacy of a dual-step pharmacological intervention in attenuating traumatic-like memories, even in a context different from the original learning environment.

4.
Br J Pharmacol ; 181(11): 1671-1689, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38320596

ABSTRACT

BACKGROUND AND PURPOSE: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats. EXPERIMENTAL APPROACH: We focused on the 5-HT1A and 5-HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. KEY RESULTS: A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. CONCLUSION AND IMPLICATIONS: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.


Subject(s)
Banisteriopsis , Extinction, Psychological , Fear , Receptor, Serotonin, 5-HT1A , Receptor, Serotonin, 5-HT2A , Animals , Fear/drug effects , Fear/physiology , Male , Receptor, Serotonin, 5-HT1A/metabolism , Receptor, Serotonin, 5-HT1A/drug effects , Receptor, Serotonin, 5-HT2A/metabolism , Receptor, Serotonin, 5-HT2A/drug effects , Extinction, Psychological/drug effects , Rats , Banisteriopsis/chemistry , Hallucinogens/pharmacology , Hallucinogens/administration & dosage , Rats, Sprague-Dawley , Behavior, Animal/drug effects , Pyridines/pharmacology
5.
Int J Biol Macromol ; 262(Pt 1): 129823, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38296146

ABSTRACT

The crosslinking of the polymer matrix with compatible macromolecules results in a three-dimensional network structure that offers an enhancement in the controlled release properties of the material. In this sense, this work aimed to improve the release profile of mefenamic acid (MAC) through crosslinking strategies. κ-Carrageenan/sericin crosslinked blend was obtained by covalent and thermal crosslinking and the different formulations were characterized. The gastroresistant potential and release profile were evaluated in the dissolution assay. The effect and characterization of the particles were investigated. Multiple units presented high entrapment efficiency (94.11-104.25), high drug loading (36.50-47.50 %) and adequate particle size (1.34-1.57 mm) with rough surface and visually spherical shape. The Weibull model showed that drug release occurred by relaxation, erosion and Fickian diffusion. Material stability and absence of MAC -polymer interactions were demonstrated by FTIR and thermogravimetric analysis. DSC showed a stable character of MAC in the drug-loaded beads. Moreover, the application studies of κ-Car/Ser/carboxymethylcellulose in the in vitro intestine mode showed that the crosslinked blend increased cell viability (>85 %), while free MAC exhibited a cytotoxic effect. Finally, the crosslinked k-Car/Ser blend MAC -loaded showed promising properties of a sustained release form of anti-inflammatory drug.


Subject(s)
Sericins , Sericins/chemistry , Mefenamic Acid/pharmacology , Polymers , Carrageenan/chemistry , Drug Liberation , Delayed-Action Preparations/chemistry
6.
Int J Biol Macromol ; 246: 125558, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37392907

ABSTRACT

Modified release of multiparticulate pharmaceutical forms is a key therapeutic strategy to reduce side effects and toxicity caused by high and repeated doses of immediate-release oral drugs. This research focused on the encapsulation of indomethacin (IND) in the crosslinked k-Car/Ser polymeric matrix by covalent and thermal methods to evaluate drug delivery modulation and properties of the crosslinked blend. Therefore, the entrapment efficiency (EE %), drug loading (DL %) and physicochemical properties of the particles were investigated. The particles presented a spherical shape and a rough surface with a mean diameter of 1.38-2.15 mm (CCA) and 1.56-1.86 mm (thermal crosslink). FTIR investigation indicated the presence of IDM in the particles and X-ray pattern showed the maintenance of crystallinity of IDM. The in vitro release in acidic medium (pH 1.2) and phosphate buffer saline solution (pH 6.8) was 1.23-6.81 % and 81-100 %, respectively. Considering the results, the formulations remained stable after 6 months. The Weibull equation was adequately fitted for all formulations and a diffusion mechanism, swelling and relaxation of chain were observed. IDM-loaded k-carrageenan/sericin/CMC increases cell viability (> 75 % for neutral red and > 81 % for MTT). Finally, all formulations present gastro-resistance, pH response and altered release and have the potential to be used as drug delivery careers.


Subject(s)
Indomethacin , Sericins , Indomethacin/chemistry , Carrageenan , Pharmaceutical Preparations , Drug Delivery Systems
7.
Pharmaceutics ; 15(4)2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37111770

ABSTRACT

Doxycycline (DX) is a well-established and broad-spectrum antimicrobial drug. However, DX has drawbacks, such as physicochemical instability in aqueous media and bacterial resistance. The inclusion of drugs in cyclodextrin complexes and their loading into nanocarriers can overcome these limitations. Thus, we studied the DX/sulfobutylether-ß-CD (SBE-ß-CD) inclusion complex for the first time and used it to reticulate chitosan. The resulting particles were evaluated by their physicochemical characteristics and antibacterial activity. DX/SBE-ß-CD complexes were characterized by nuclear magnetic resonance, infrared spectroscopy, thermal analysis, X-ray diffraction, and scanning electron microscopy (SEM), whereas DX-loaded nanoparticles were characterized by dynamic light scattering, SEM, and drug content. The partial inclusion of the DX molecule in CD happened in a 1:1 proportion and brought increased stability to solid DX upon thermal degradation. Chitosan-complex nanoparticles measured approximately 200 nm, with a narrow polydispersity and particles with sufficient drug encapsulation for microbiological studies. Both formulations preserved the antimicrobial activity of DX against Staphylococcus aureus, whereas DX/SBE-ß-CD inclusion complexes were also active against Klebsiella pneumoniae, indicating the potential use of these formulations as drug delivery systems to treat local infections.

8.
Int J Biol Macromol ; 232: 123381, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36731703

ABSTRACT

This study aimed to develop a natural and multiparticulate carrier of k-carrageenan (k-Car) and sericin (Ser) for encapsulation of indomethacin (IND) in order to minimize gastrointestinal effects caused by immediate-release. Increasing the amount of IND in the formulations subtly reduced the entrapment efficiency (EE) and drug loading (DL) due to matrix saturation. Sericin was essential to improve EE and DL when compared to pure k-Car (EE > 90 % and DL > 47 %) with suitable particle sizes (1.3461 ± 0.1891-1.7213 ± 0.1586 mm). The incorporation and integrity of IND in the particles were confirmed by analytical techniques of HPLC, XRD, FTIR, and SEM. Additionally, the k-Car/Ser matrix was pH-responsive with low IND release at pH 1.2 and extended-release at pH 6.8. The Weibull model had an adequate fit to the experimental data with R2aju 0.950.99 and AIC 82.4-24.9, with curves in parabolic profile (b < 1) and indicative of a controlled drug-release mechanism by diffusion. Besides, k-Car/Ser/IND and placebo were not cytotoxic (cell viability > 85 % at 150-600 µM) for the Caco-2 cell line. Therefore, the polymeric matrix is gastro-resistant, stable, and biocompatible to carry indomethacin and deliver it to the intestinal environment.


Subject(s)
Indomethacin , Sericins , Humans , Indomethacin/pharmacology , Carrageenan , Polymers , Caco-2 Cells , Drug Delivery Systems
9.
Nutr Rev ; 81(10): 1310-1320, 2023 09 11.
Article in English | MEDLINE | ID: mdl-36779324

ABSTRACT

CONTEXT: A recent US national survey of the health status of the male transgender population has raised awareness about the little-studied relationship between testosterone hormone therapy in transgender men and cardiovascular outcomes. OBJECTIVE: The aim of this systematic review was to assess the relationship between cross-sex hormone therapy in transgender men and lipid profiles and cardiovascular risk. DATA SOURCES: The PubMed, SciELO, SpringerLink, and EBSCOhost databases were searched up to March 2021 for studies assessing the association between cross-sex hormone therapy and the incidence of outcomes related to cardiovascular disease in transgender men over 18 years of age . DATA EXTRACTION: Data extracted were sorted into clinical data (systolic, diastolic, and mean blood pressure), anthropometric data (body mass index, weight, waist circumference, fat mass, and lean mass), and biochemical data (triglycerides, total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], very low-density lipoprotein cholesterol [VLDL-C], and the HDL-C to LDL-C ratio). DATA ANALYSIS: Study quality was appraised independently by two reviewers using the Cochrane tools for assessment of methodological quality or risk of bias in nonrandomized studies, and the Newcastle-Ottawa Scale was applied. Of 735 studies identified, 11 were included in the review. Most studies reported no change in cholesterol or triglyceride levels after hormone treatment. A reduction in HDL-C levels was observed in 7 of 11 studies, although this alone cannot be considered a cardiovascular risk factor. Likewise, clinical and anthropometric findings showed no changes predictive of cardiovascular risk. CONCLUSIONS: Although these findings suggest that hormone therapy may lead to a decrease in HDL-C levels and an increase in LDL-C levels, they are insufficient to establish a relationship with cardiovascular disease. Furthermore, no significant effects on metabolic and anthropometric values were found. Further studies with higher quality and longer follow-up periods are needed to establish cardiovascular risk. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD 42020212560.


Subject(s)
Cardiovascular Diseases , Transgender Persons , Humans , Male , Adult , Adolescent , Cholesterol, LDL , Cardiovascular Diseases/epidemiology , Cholesterol , Triglycerides , Cholesterol, HDL , Gonadal Steroid Hormones , Risk Factors
10.
Colloids Surf B Biointerfaces ; 222: 113043, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36455361

ABSTRACT

Nanocarriers can deliver drugs to specific organs or cells, potentially bridging the gap between a drug's function and its interaction with biological systems such as human physiology. The untapped potential of nanotechnology stems from its ability to manipulate materials, allowing control over physical and chemical properties and overcoming drug-related problems, e.g., poor solubility or poor bioavailability. For example, most protein drugs are administered parenterally, each with challenges and peculiarities. Some problems faced by bioengineered macromolecule drugs leading to poor bioavailability are short biological half-life, large size and high molecular weight, low permeability through biological membranes, and structural instability. Nanotechnology emerges as a promising strategy to overcome these problems. Nevertheless, the delivery system should be carefully chosen considering loading efficiency, physicochemical properties, production conditions, toxicity, and regulations. Moving from the bench to the bedside is still one of the major bottlenecks in nanomedicine, and toxicological issues are the greatest challenges to overcome. This review provides an overview of biotech drug delivery approaches, associated nanotechnology novelty, toxicological issues, and regulations.


Subject(s)
Nanoparticles , Nanotechnology , Humans , Drug Delivery Systems , Nanomedicine , Pharmaceutical Preparations/chemistry , Proteins , Macromolecular Substances , Nanoparticles/chemistry
11.
Neuropharmacology ; 223: 109316, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36334768

ABSTRACT

Growing evidence from male rodent and human studies suggests that cannabidiol (CBD) modulates the expression of aversive memories and anxiety-related responses. The limited data on whether and how CBD influences these aspects in females could have therapeutic implications given the increased susceptibility of women to anxiety- and stress-related disorders relative to men. Female studies are also essential to examine inherent aspects that potentially contribute to differences in responsiveness to CBD. Here we addressed these questions in adult female rats. Contextually fear-conditioned animals acutely treated with CBD (1.0-10 mg/kg) were tested 45 min later. In subsequent experiments, we investigated the estrous cycle effects and the contribution of dorsal hippocampus (DH) serotonin 1A (5-HT1A) and cannabinoid types 1 (CB1) and 2 (CB2) receptors to CBD-induced effects on memory retrieval/expression. The effects of pre-retrieval systemic or intra-DH CBD administration on subsequent fear extinction were also assessed. Lastly, we evaluated the open arms avoidance and stretched-attend postures in females exposed to the elevated plus-maze after systemic CBD treatment. CBD 3.0 and 10 mg/kg administered before conditioned context exposure reduced females' freezing. This action remained unchanged across the estrous cycle and involved DH 5-HT1A receptors activation. Pre-retrieval CBD impaired memory reconsolidation and lowered fear during early extinction. CBD applied directly to the DH was sufficient to reproduce the effects of systemic CBD treatment. CBD 3.0 and 10 mg/kg reduced anxiety-related responses scored in the elevated plus-maze. Our findings demonstrate that CBD attenuates the behavioral manifestation of learned fear and anxiety in female rats.


Subject(s)
Cannabidiol , Cannabinoids , Humans , Rats , Animals , Female , Male , Cannabidiol/pharmacology , Fear/physiology , Extinction, Psychological , Serotonin/metabolism , Cannabinoids/pharmacology , Receptor, Cannabinoid, CB2 , Receptor, Cannabinoid, CB1
12.
Pharmaceuticals (Basel) ; 15(10)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36297398

ABSTRACT

Wound healing is known to be a complicated and intricate process and commonly classified as chronic or acute. Patients with chronic wounds are of public health concern, and require more attention onto skin lesions, including atopic dermatitis. Despite being a natural process, healing can be impaired by existing chronic de diseases such as diabetes, for example. Recently, wound dressings based in nanotechnology systems have emerged as a viable option to improve the healing process. Current advances in nanotechnology-based systems to release growth factors and bioactive agents represent a great opportunity to develop new therapies for wound treatments. It is essential that healthcare professionals understand the key processes involved in the healing cascade, to maximize care with these patients and minimize the undesirable outcomes of non-healing wounds. Therefore, this review aims to summarize the healing process phases and provide a general overview of dressings based in nanotechnology using biomaterials for the release of active agents in wound site.

13.
Int J Pharm ; 626: 122193, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-36108993

ABSTRACT

The first step of a successful nanoformulation development is preformulation studies, in which the best excipients, drug-excipient compatibility and interactions can be identified. During the formulation, the critical process parameters and their impact must be studied to establish the stable system with a high drug entrapment efficiency (EE). This work followed these steps to develop nanostructured lipid carriers (NLCs) to deliver the antibiotic levofloxacin (LV). The preformulation studies covered drug solubility in excipients and thorough characterization using thermal analysis, X-ray diffraction and spectroscopy. A design of experiment based on the process parameters identified nanoparticles with < 200 nm in size, polydispersity <= 0.3, zeta potential -21 to -24 mV, high EE formulations (>71 %) and an acceptable level of LV degradation products (0.37-1.13 %). To the best of our knowledge, this is the first time that a drug degradation is reported and studied in work on nanostructured lipids. LV impurities following the NLC production were detected, mainly levofloxacin N-oxide, a degradation product that has no antimicrobial activity and could interfere with LV quantification in spectrophotometric experiments. Also, the achievement of the highest EE in lipid nanoparticles than those described in the literature to date and the apparent protective action of NLC of entrapped-LV against degradation are important findings.


Subject(s)
Nanoparticles , Nanostructures , Anti-Bacterial Agents , Drug Carriers/chemistry , Excipients/chemistry , Levofloxacin , Lipids/chemistry , Liposomes , Nanoparticles/chemistry , Nanostructures/chemistry , Oxides , Particle Size
14.
Lancet Reg Health Am ; 13: 100319, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35874497

ABSTRACT

Background: Chronic social and health inequities faced by indigenous peoples in Brazil foretell the detrimental impact of COVID-19. Methods: We use de-identified, publicly available data from the Ministry of Health from March/2020 - December/2021 to describe vaccination coverage, cumulative incidence, and cumulative mortality rates due to COVID-19 among indigenous peoples. We also compare vaccination coverage among indigenous peoples with that reported for older adults, who were simultaneously included as a priority group in the vaccination strategy. Finally, we compared COVID-19 incidence and mortality rates in the indigenous population with that reported for the general Brazilian population. Findings: We found important heterogeneities in vaccination coverage across the 34 indigenous districts, and a lower overall coverage among indigenous peoples compared to older adults. We observed higher COVID-19 cumulative incidence rates among indigenous populations compared to the general Brazilian population. Although mortality rates were seemingly lower, data should be interpreted with caution due to a younger age structure and more frequent underreporting of cases and deaths among indigenous populations. After the beginning of COVID-19 vaccination program, we observed a decrease in both incidence and mortality rates among indigenous peoples in all Brazilian regions. Interpretation: The COVID-19 pandemic has had a heavy toll on vulnerable populations. Although social and geographic isolation challenges the implementation of any vaccination program for indigenous populations, prior experience suggests that the COVID-19 vaccination strategy lacked effectiveness. The absence of a coordinated strategy to reinforce the importance of the vaccine and other prevention methods, to guarantee the access to trustworthy information, and to respond with the necessary resources in extreme situations, resulted in lower COVID-19 vaccination coverage, higher incidence rates, and preventable deaths due to COVID-19 among indigenous peoples in Brazil. Funding: This work was not supported by specific funding.

15.
Int J Pharm ; 618: 121655, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35283220

ABSTRACT

Doxycycline (DX) is a well-established antimicrobial drug that has been used since 1967 to treat several diseases. This drug has a wide therapeutic range, acting as antibacterial, antiviral, antiparasitic, and anticancer agent, including its neuroprotective, anti-inflammatory, and wound healing effects. However, DX is unstable in the physiological environment, presenting poor cellular penetration and adverse effects related to gastrointestinal irritation. As for practically all antibiotics, bacteria can develop resistance to this drug. Pharmaceutical nanotechnology proved to be a promising strategy to overcome these drawbacks. Thus, this review addresses scientific studies regarding formulations of DX-loaded nanoparticles (DX-NPs) for therapy use. Formulations with different materials, manufacturing methods, and biomedical applications are described and discussed to understand NPs contribution for in vitro and in vivo DX performance.


Subject(s)
Anti-Infective Agents , Nanoparticles , Anti-Bacterial Agents , Doxycycline , Drug Delivery Systems/methods , Nanotechnology
16.
Pharmaceutics ; 15(1)2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36678715

ABSTRACT

Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of dispersions often result in a reduced lifespan, which limits their availability on the market. Solid formulations obtained by freeze-drying can immobilize vesicles and provide extended shelf life. For both processes, the choice of excipients and process parameters are crucial to protect the carrier layers against tension caused by freezing and/or dehydration. The aim of this work is to evaluate the influence of freezing and drying parameters, besides excipient choice, to obtain solid long-circulating and fusogenic liposomes (LCFL-PTX/DXR) co-encapsulating paclitaxel (PTX) and doxorubicin (DXR) at a synergistic ratio (1:10). METHODS: LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg'), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy. RESULTS: Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5-7% of moisture content (200-240 nm); 44-60% of PTX retention, and 25-35% of DXR retention, with the variations caused by cryoprotector concentration and process changes. CONCLUSIONS: Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.

17.
Braz. J. Pharm. Sci. (Online) ; 58: e191042, 2022. tab, graf
Article in English | LILACS | ID: biblio-1394057

ABSTRACT

Abstract L-Asparaginase (L-ASNase) is a biopharmaceutical used for acute lymphoblastic leukaemia (ALL) treatment, dramatically increasing the patients' chance of cure. However, its production and distribution in developing countries were disrupted because of its low profitability, which caused great concern among patients. This study evaluates the feasibility of combining fractional precipitation and aqueous two-phase systems (ATPS) to purify L-ASNase from a low-grade product, commercially known as Acrylaway® L. The ATPS purification results were not particularly expressive compared to the two-step purification process composed of ethanol precipitation and gel filtration, which was able to recover the target molecule with a purification factor over 5 fold. Thus, we studied a purification process capable of manufacturing pharmaceutical grade L-ASNase from a commercially available low-grade raw material; however, improvements regarding its throughput must be achieved, and high purity is the first step to apply it as a new biopharmaceutical product. The proposed process could pose as a short-time solution to mitigate its shortage while a cost-effective production plant is being developed.


Subject(s)
Asparaginase/isolation & purification , Fractional Precipitation/methods , Antineoplastic Agents/isolation & purification , Feasibility Studies , Chromatography, Gel , Cost-Benefit Analysis
18.
Sci Rep ; 11(1): 10195, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33986357

ABSTRACT

For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.


Subject(s)
Bromelains/chemistry , Bromelains/metabolism , Bromelains/pharmacology , Antioxidants , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Chitosan/chemistry , Chitosan/pharmacology , Drug Delivery Systems , Humans , Nanoparticles/chemistry , Wound Healing/drug effects
19.
Int J Pharm ; 604: 120534, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33781887

ABSTRACT

Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.


Subject(s)
Curcumin , Nanostructures , Neoplasms , Biological Availability , Humans , Micelles , Neoplasms/drug therapy
20.
Demetra (Rio J.) ; 16(1): e57854, 2021.
Article in English, Portuguese | LILACS | ID: biblio-1428147

ABSTRACT

Objetivo:O objetivo deste estudo foi avaliar o uso de um tempero à base de ervas em preparações proteicas como estratégia para a redução da ingestão de sódio por comensais atendidos em uma Unidade de Alimentação e Nutrição (UAN). Material e Métodos:Trata-se de um estudo transversal realizado em uma UAN de uma fábrica. O tempero à base de ervas foi desenvolvido com o auxílio das cozinheiras da unidade. A composição nutricional das preparações proteicas foi determinada com o auxílio de tabelas de composição de alimentos. Para avaliar a aceitação das preparações, foram realizadas análises sensoriais de duas preparações culinárias: peito de frango e acém bovino adicionados do tempero à base de ervas. Foram considerados os seguintes atributos: cor, textura, aroma, aparência e avaliação global, em uma escala hedônica de 9 pontos que varia de "desgostei muitíssimo" a "gostei muitíssimo". O índice de aceitabilidade também foi calculado para todos os atributos. Resultados: Quarenta e um juízes consumidores foram recrutados para realizar a análise sensorial. Houve uma redução importante nos níveis de sódio de 60,2% (de 939,2 mg para 375,3 mg) e 23,3% (de 709,7 mg para 544,0 mg) por 100g de peito de frango e acém bovino, respectivamente, e um aumento no teor de fibra das preparações que receberam o tempero à base de ervas. O índice de aceitação global de peito de frango temperado e filé de carne bovina foi de 87,8% e 83,8%, respectivamente. Conclusão: A substituição de temperos ultraprocessados por temperos à base de ervas em preparações de proteínas foi bem aceita entre comensais da UAN.


Objective:This study aimed to evaluate the use of a herbs-based seasoning in protein preparations as a strategy for reducing sodium intake by diners served at a Food and Nutrition Unit (FNU). Material and Methods: This was a cross-sectional study carried out in a FNU factory. The herbs-based seasoning was developed with the help of the unit's cooks. The proximate composition of protein preparations was determined with the aid of food composition tables. To assess the acceptance of the preparations, a sensory analysis was performed for two culinary preparations: chicken breast and beef chuck steak added with the herbs-based seasoning. The following attributes were considered for evaluating colour, texture, aroma, appearance and overall evaluation, on a 9-point hedonic scale ranging from "I disliked a lot" to "I liked a lot". The acceptability index was also calculated for all attributes. Results: Forty-one consumer judges were recruited to perform the sensory analysis. There was an important reduction in sodium levels of 60.2% (from 939.2 mg to 375.3 mg) and 23.3% (from 709.7 mg to 544.0 mg) per 100g of chicken breast and beef chuck steak, respectively, and an increase in the fiber content of the preparations that received the herbs-based seasoning. The global acceptance index of seasoned chicken breast and beef chuck steak was 87.8% and 83.8%, respectively. Conclusion: The substitution of ultra-processed seasoning for herbs-based seasoning in protein preparations was well accepted among FNU diners.


Subject(s)
Humans , Sodium Chloride, Dietary , Collective Feeding , Food Composition , Prepared Foods , Diet, Healthy , Brazil
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