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1.
Int J Pharm ; 641: 123058, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37207858

RESUMO

3D Printing is an innovative technology within the pharma and food industries that allows the design and manufacturing of novel delivery systems. Orally safe delivery of probiotics to the gastrointestinal tract faces several challenges regarding bacterial viability, in addition to comply with commercial and regulatory standpoints. Lactobacillus rhamnosus CNCM I-4036 (Lr) was microencapsulated in generally recognised as safe (GRAS) proteins, and then assessed for robocasting 3D printing. Microparticles (MP-Lr) were developed and characterised, prior to being 3D printed with pharmaceutical excipients. MP-Lr showed a size of 12.3 ± 4.1 µm and a non-uniform wrinkled surface determined by Scanning Electron Microscopy (SEM). Bacterial quantification by plate counting accounted for 8.68 ± 0.6 CFU/g of live bacteria encapsulated within. Formulations were able to keep the bacterial dose constant upon contact with gastric and intestinal pH. Printlets consisted in oval-shape formulations (15 mm × 8 mm × 3.2 mm) of ca. 370 mg of total weight, with a uniform surface. After the 3D printing process, bacterial viability remained even as MP-Lr protected bacteria alongside the process (log reduction of 0.52, p > 0.05) in comparison with non-encapsulated probiotic (log reduction of 3.05). Moreover, microparticle size was not altered during the 3D printing process. We confirmed the success of this technology for developing an orally safe formulation, GRAS category, of microencapsulated Lr for gastrointestinal vehiculation.


Assuntos
Lacticaseibacillus rhamnosus , Probióticos , Trato Gastrointestinal , Intestinos/microbiologia , Viabilidade Microbiana , Impressão Tridimensional
2.
Pharmaceutics ; 15(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37111524

RESUMO

P2Et is the standardized extract of Caesalpinia spinosa (C. spinosa), which has shown the ability to reduce primary tumors and metastasis in animal models of cancer, by mechanisms involving the increase in intracellular Ca++, reticulum stress, induction of autophagy, and subsequent activation of the immune system. Although P2Et has been shown to be safe in healthy individuals, the biological activity and bioavailability can be increased by improving the dosage form. This study investigates the potential of a casein nanoparticle for oral administration of P2Et and its impact on treatment efficacy in a mouse model of breast cancer with orthotopically transplanted 4T1 cells. Animals were treated with either free or encapsulated oral P2Et orally or i.p. Tumor growth and macrometastases were evaluated. All P2Et treatments significantly delayed tumor growth. The frequency of macrometastasis was reduced by 1.1 times with P2Et i.p., while oral P2Et reduced it by 3.2 times and nanoencapsulation reduced it by 3.57 times. This suggests that nanoencapsulation led to higher doses of effective P2Et being delivered, slightly improving bioavailability and biological activity. Therefore, the results of this study provide evidence to consider P2Et as a potential adjuvant in the treatment of cancer, while the nanoencapsulation of P2Et provides a novel perspective on the delivery of these functional ingredients.

3.
Pharmaceutics ; 13(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803271

RESUMO

Curcumin is a natural compound obtained from turmeric root with high antioxidant and anti-inflammatory activities. However, clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation. This study was conducted to evaluate the effect of curcumin incorporation in zein nanoparticles on the pharmacokinetic parameters of systemic curcumin in plasma. Wistar rats were administered a single oral dose of 250 mg/kg of standard curcumin (control) or nanocurcumin (zein-based nanoparticles, Nucaps). The proposed new formulation was also compared with two commercially available curcumin complexes. Blood samples were collected at different times, and plasma levels were determined using HPLC-MS/MS. Overall, nanocurcumin (Nucaps) formulation was well tolerated and showed a 9-fold increase in oral bioavailability when compared to the standard curcumin natural extract. In addition, the nanoparticles prepared in this study demonstrated a bioavailability profile superior to that of other bioavailability-enhanced curcumin complexes currently available in the marketplace. Thus, our nanoparticle-based formulation has shown great potential as a nutraceutical for the oral administration of curcumin.

4.
J Pharm Sci ; 108(7): 2421-2429, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30849462

RESUMO

Peanut allergy is one of the most prevalent and severe of food allergies with no available cure. The aim of this work was to evaluate the potential of an oral immunotherapy based on the use of a roasted peanut extract encapsulated in nanoparticles with immunoadjuvant properties. For this, a polymer conjugate formed by the covalent binding of mannosamine to the copolymer of methyl vinyl ether and maleic anhydride was first synthetized and characterized. Then, the conjugate was used to prepare nanoparticles with an important capability to diffuse through the mucus layer and reach, in a large extent, the intestinal epithelium, including Peyer's patches. Their immunotherapeutic potential was evaluated in a model of presensitized CD1 mice to peanut. After completing therapy, mice underwent an intraperitoneal challenge with peanut extract. Nanoparticle-treatment was associated with both less serious anaphylaxis symptoms and higher survival rates than control, confirming the protective effect of this formulation against the challenge.


Assuntos
Arachis/imunologia , Nanopartículas/química , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/terapia , Adjuvantes Imunológicos/farmacologia , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Fatores Imunológicos/imunologia , Imunoterapia/métodos , Masculino , Camundongos , Polímeros/química , Ratos , Ratos Wistar
5.
Expert Opin Drug Deliv ; 15(7): 675-686, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-27732129

RESUMO

INTRODUCTION: Allergic diseases constitute one of the most common causes of chronic illness in developed countries. The main mechanism determining allergy is an imbalance between Th1 and Th2 response towards Th2. AREAS COVERED: This review describes the mechanisms underlying the natural tolerance to food components and the development of an allergic response in sensitized individuals. Furthermore, therapeutic approaches proposed to manage these abnormal immunologic responses food are also presented and discussed. EXPERT OPINION: In the past, management of food allergies has consisted of the education of patients to avoid the ingestion of the culprit food and to initiate the therapy (e.g. self-injectable epinephrine) in case of accidental ingestion. In recent years, sublingual/oral immunotherapies based on the continuous administration of small amounts of the allergen have been developed. However, the long periods of time needed to obtain significant desensitization and the generation of adverse effects, limit their use. In order to solve these drawbacks, strategies to induce tolerance are being studied, such as the use of either adjuvant immunotherapy in order to facilitate the reversion of the Th2 response towards Th1 or the use of monoclonal antibodies to block the main immunogenic elements.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/tratamento farmacológico , Tolerância Imunológica/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Dessensibilização Imunológica/métodos , Epinefrina/administração & dosagem , Humanos
6.
Int J Biol Macromol ; 110: 328-335, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28965967

RESUMO

The aim of this work was to evaluate the potential application of an original oral immunotherapy, based on the use of nanoparticles, against an experimentally induced peanut allergy. In this context, a roasted peanut extract, containing the main allergenic proteins, were encapsulated into poly(anhydride) nanoparticles. The resulting peanut-loaded nanoparticles (PE-NP) displayed a mean size of about 150nm and a significantly lower surface hydrophobicity than empty nanoparticles (NP). This low hydrophobicity correlated well with a higher in vitro diffusion in pig intestinal mucus than NP and an important in vivo capability to reach the intestinal epithelium and Peyer's patches. The immunotherapeutic capability of PE-NP was evaluated in a model of pre-sensitized CDI mice to peanut. After completing therapy of three doses of peanut extract, either free or encapsulated into nanoparticles, mice underwent an intraperitoneal challenge. Anaphylaxis was evaluated by means of assessment of symptom scores and mouse mast cell protease-1 levels (mMCPT-1). PE-NP treatment was associated with significant lower levels of mMCPT-1, and a significant survival rate after challenge, confirming the protective effect of this formulation against the challenge. In summary, this nanoparticle-based formulation might be a valuable strategy for peanut-specific immunotherapy.


Assuntos
Alérgenos , Arachis/química , Dessensibilização Imunológica/métodos , Nanopartículas , Hipersensibilidade a Amendoim/tratamento farmacológico , Proteínas de Plantas , Administração Oral , Alérgenos/química , Alérgenos/farmacocinética , Alérgenos/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/patologia , Proteínas de Plantas/química , Proteínas de Plantas/farmacocinética , Proteínas de Plantas/farmacologia
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