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1.
Int J Nanomedicine ; 19: 5139-5156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859954

RESUMO

Introduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs. Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated. Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice. Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.


Assuntos
Derivados de Hidroxietil Amido , Hiperuricemia , Luteolina , Nanopartículas , Animais , Nanopartículas/química , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacocinética , Derivados de Hidroxietil Amido/administração & dosagem , Derivados de Hidroxietil Amido/farmacologia , Luteolina/farmacocinética , Luteolina/farmacologia , Luteolina/química , Luteolina/administração & dosagem , Camundongos , Células CACO-2 , Hiperuricemia/tratamento farmacológico , Hiperuricemia/sangue , Humanos , Masculino , Tamanho da Partícula , Modelos Animais de Doenças , Solubilidade , Ácido Úrico/sangue , Ácido Úrico/química , Disponibilidade Biológica , Administração Oral , Estabilidade de Medicamentos
2.
AAPS PharmSciTech ; 25(5): 135, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862657

RESUMO

Lutein (Lut) is a recognized nutritional supplement known for its antioxidative and anti-inflammatory properties, crucial in mitigating ocular disease. However, enhancements to Lut stability and solubility remain challenges to be addressed in the healthcare industry. Herein, we fabricated and evaluated a food-grade highly porous ß-cyclodextrin metal-organic framework (ß-CD-MOF) for its ability to encapsulate Lut. Lut stability considerably improved when loaded into ß-CD-MOF to form a Lut@ß-CD-MOF complex, which exhibited better stability than Lut loaded into the γ-cyclodextrin metal-organic framework (Lut@γ-CD-MOF), Lut@ß-CD, and commercial product (Blackmores™) at 40°C, 60°C, and 70°C, respectively. The solubility of Lut@ß-CD-MOF in water increased by 26.8-fold compared to raw Lut at 37°C. Lut@ß-CD-MOF exhibited greater hydrophilicity, as determined by measuring the water contact angle. Molecular docking and other characterizations of Fourier transform infrared spectroscopy and powder X-ray diffraction confirmed that Lut was successfully encapsulated in the chamber formed by the three cyclodextrins in ß-CD-MOF. Thermogravimetric analysis and Raman spectroscopy demonstrated that Lut distributed in the ß-CD-MOF cavity deeply improved Lut stability and solubility. In conclusion, our findings underscored the function of ß-CD-MOF in enhancing Lut stability and solubility for formulation applications.


Assuntos
Luteína , Estruturas Metalorgânicas , Solubilidade , beta-Ciclodextrinas , Estruturas Metalorgânicas/química , beta-Ciclodextrinas/química , Luteína/química , Estabilidade de Medicamentos , Difração de Raios X/métodos , Simulação de Acoplamento Molecular/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Interações Hidrofóbicas e Hidrofílicas , Porosidade
3.
AAPS PharmSciTech ; 25(5): 136, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862810

RESUMO

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.


Assuntos
Canabidiol , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Emulsões , Solubilidade , Canabidiol/química , Canabidiol/administração & dosagem , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Administração Oral , Química Farmacêutica/métodos , Tecnologia de Extrusão por Fusão a Quente/métodos , Liberação Controlada de Fármacos , Tamanho da Partícula , Disponibilidade Biológica , Composição de Medicamentos/métodos , Polietilenoglicóis/química , Estabilidade de Medicamentos , Óleo de Gergelim/química , Polivinil
4.
AAPS PharmSciTech ; 25(5): 128, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844721

RESUMO

In this paper, we report two Accelerated Stability Assessment Program (ASAP) studies for a pediatric drug product. Whereas the first study using a generic design failed to establish a predictive model, the second one was successful after troubleshooting the first study and customizing the study conditions. This work highlighted important lessons learned from designing an ASAP study for formulations containing excipients that could undergo phase change at high humidity levels. The stability predictions by the second ASAP model were consistent with available long-term stability data of the drug product under various storage conditions in two different packaging configurations. The ASAP model was part of the justifications accepted by the health authority to submit a stability package with reduced long-term stability data from the primary stability batches for a Supplemental New Drug Application (sNDA).


Assuntos
Química Farmacêutica , Estabilidade de Medicamentos , Excipientes , Excipientes/química , Química Farmacêutica/métodos , Umidade , Armazenamento de Medicamentos , Embalagem de Medicamentos/métodos , Embalagem de Medicamentos/normas , Composição de Medicamentos/métodos , Humanos , Criança , Preparações Farmacêuticas/química , Pediatria/métodos
5.
Int J Biol Macromol ; 272(Pt 2): 132903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848840

RESUMO

Fenofibrate (FNF) is used to treat hyperlipidemia. However, FNF is a poorly water-soluble drug, and the dosage of commercial products is relatively high at 160 mg in a Lipidil® tablet. Therefore, this study aimed to develop an FNF-solid dispersion (SD) that solubilizes and stabilizes FNF. The melting method that uses the low melting point of FNF was employed. The dissolution percentage of FNF in the optimal formulation (SD2) increased by 1.2-, 1.3-, and 1.3-fold at 5 min compared to that of Lipidil® and increased by 2.0-, 2.1-, and 2.0-fold compared to the pure FNF in pH 1.2 media, distilled water, and pH 6.8 buffer, which included 0.025 M sodium lauryl sulfate, respectively. The SD2 formulation showed a dissolution percentage of nearly 100 % in all dissolution media after 60 min. The physicochemical properties of the SD2 formulation exhibited slight changes in the melting point and crystallinity of FNF. Moreover, the stability of the SD2 formulation was maintained for six months. In particular, it was challenging to secure stability when starch#1500 was excluded from the SD2 formulation. In conclusion, the dissolution percentage of FNF in the SD2 formulation was improved owing to the weak binding force between FNF and the excipients, stability was secured, and favorable results are expected in future animal experiments.


Assuntos
Fenofibrato , Solubilidade , Amido , Fenofibrato/química , Amido/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Temperatura de Transição , Química Farmacêutica/métodos , Concentração de Íons de Hidrogênio , Hipolipemiantes/química
7.
J Pharm Biomed Anal ; 247: 116256, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38850847

RESUMO

A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe3+ in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug-excipient interaction between bromhexine and tartaric acid with Fe3+. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.


Assuntos
Bromoexina , Contaminação de Medicamentos , Excipientes , Bromoexina/química , Bromoexina/análise , Cromatografia Líquida de Alta Pressão/métodos , Excipientes/química , Excipientes/análise , Tartaratos/química , Tartaratos/análise , Espectrometria de Massas/métodos , Estabilidade de Medicamentos , Controle de Qualidade
8.
Appl Microbiol Biotechnol ; 108(1): 359, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836885

RESUMO

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.


Assuntos
Doença de Newcastle , Vírus da Doença de Newcastle , Temperatura , Vacinas Virais , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/química , Projetos Piloto , Doença de Newcastle/prevenção & controle , Doença de Newcastle/virologia , Vacinas Virais/química , Vacinas Virais/imunologia , Vácuo , Animais , Galinhas , Dessecação , China , Estabilidade de Medicamentos , Carga Viral
9.
PLoS One ; 19(6): e0303900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843120

RESUMO

BACKGROUND: Candesartan cilexetil (CC) is a selective angiotensin II receptor antagonist widely used to treat hypertension. CC is a substrate of P-glycoprotein (P-gp), causing its efflux to the intestinal lumen. It is also practically insoluble in water and has low oral bioavailability (14%). Thus, the current study aims to improve the in vitro dissolution of CC by developing solid dispersion systems (SDSs) and corroborating the in vitro results using a simulated pharmacokinetics study. METHODS: The SDSs were prepared using polyvinyl pyrrolidone (PVP) as a water-soluble polymer, Eudragit E100 (EE100) as a pH-dependent soluble carrier, and a combination of these two polymers. The saturation solubility and the dissolution rate studies of the prepared systems in three dissolution media were performed. The optimized system SE-EE5 was selected for further investigations, including DSC, XRD, FTIR, FESEM, DLS, TSEM, IVIVC convolution study, and stability studies. RESULTS: The solubility of CC significantly increased by a factor of 27,037.344 when formulated as a solid dispersion matrix using EE100 at a ratio of 1:5 (w/w) drug to polymer (SE-EE5 SD), compared to the solubility of the pure drug. The mechanism of solubility and dissolution rate enhancement of CC by the optimized SDS was found to be via the conversion of the crystalline CC into the amorphous form as well as nanoparticles formation upon dissolution at a pH below 5. The instrumental analysis tests showed good compatibility between CC and EE100 and there was no chemical interaction between the drug and the polymer. Moreover, the stability tests confirmed that the optimized system was stable after three months of storage at 25°C. CONCLUSION: The utilization of the solid dispersion technique employing EE 100 polymer as a matrix demonstrates significant success in enhancing the solubility, dissolution, and subsequently, the bioavailability of water-insoluble drugs like CC.


Assuntos
Benzimidazóis , Compostos de Bifenilo , Polímeros , Solubilidade , Tetrazóis , Benzimidazóis/química , Benzimidazóis/farmacocinética , Tetrazóis/química , Tetrazóis/farmacocinética , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacocinética , Polímeros/química , Polímeros/farmacocinética , Povidona/química , Água/química , Concentração de Íons de Hidrogênio , Disponibilidade Biológica , Estabilidade de Medicamentos , Liberação Controlada de Fármacos , Acrilatos
10.
Int J Nanomedicine ; 19: 5071-5094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846644

RESUMO

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.


Assuntos
Disponibilidade Biológica , Docetaxel , Estabilidade de Medicamentos , Nanopartículas , Tamanho da Partícula , Soroalbumina Bovina , Docetaxel/farmacocinética , Docetaxel/química , Docetaxel/administração & dosagem , Animais , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/administração & dosagem , Nanopartículas/química , Taxoides/farmacocinética , Taxoides/química , Taxoides/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratos Sprague-Dawley , Masculino , Composição de Medicamentos/métodos , Ratos
11.
Anal Chem ; 96(24): 9935-9943, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38847283

RESUMO

Biopharmaceuticals, such as monoclonal antibodies (mAbs), need to maintain their chemical and physical stability in formulations throughout their lifecycle. It is known that exposure of mAbs to light, particularly UV, triggers chemical and physical degradation, which can be exacerbated by trace amounts of photosensitizers in the formulation. Although routine assessments of degradation following defined UV dosages are performed, there is a fundamental lack of understanding regarding the intermediates, transient reactive species, and radicals formed during illumination, as well as their lifetimes and immediate impact post-illumination. In this study, we used light-coupled NMR spectroscopy to monitor in situ live spectral changes in sealed samples during and after UV-A illumination of different formulations of four mAbs without added photosensitizers. We observed a complex evolution of spectra, reflecting the appearance within minutes of transient radicals during illumination and persisting for minutes to tens of minutes after the light was switched off. Both mAb and excipient signals were strongly affected by illumination, with some exhibiting fast irreversible photodegradation and others exhibiting partial recovery in the dark. These effects varied depending on the mAb and the presence of excipients, such as polysorbate 80 (PS80) and methionine. Complementary ex situ high-performance size-exclusion chromatography analysis of the same formulations post-UV exposure in the chamber revealed significant loss of purity, confirming formulation-dependent degradation. Both approaches suggested the presence of degradation processes initiated by light but continuing in the dark. Further studies on photoreaction intermediates and transient reactive species may help mitigate the impact of light on biopharmaceutical degradation.


Assuntos
Anticorpos Monoclonais , Raios Ultravioleta , Anticorpos Monoclonais/química , Espectroscopia de Ressonância Magnética , Fotólise , Composição de Medicamentos , Estabilidade de Medicamentos , Luz
12.
Molecules ; 29(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38893485

RESUMO

The following review focuses on the manufacturing and parameterizing of ocular drug delivery systems (DDS) using polymeric materials to create soft contact lenses. It discusses the types of drugs embedded into contact lenses, the various polymeric materials used in their production, methods for assessing the mechanical properties of polymers, and techniques for studying drug release kinetics. The article also explores strategies for investigating the stability of active substances released from contact lenses. It specifically emphasizes the production of soft contact lenses modified with Cyclosporine A (CyA) for the topical treatment of specific ocular conditions. The review pays attention to methods for monitoring the stability of Cyclosporine A within the discussed DDS, as well as investigating the influence of polymer matrix type on the stability and release of CyA.


Assuntos
Ciclosporina , Liberação Controlada de Fármacos , Ciclosporina/química , Humanos , Cinética , Sistemas de Liberação de Medicamentos , Lentes de Contato Hidrofílicas , Estabilidade de Medicamentos , Polímeros/química
13.
Int J Nanomedicine ; 19: 5721-5737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895153

RESUMO

Purpose: Curcumin nanocrystals (Cur-NCs) were prepared by hot melt extrusion (HME) technology to improve the dissolution and bioavailability of curcumin (Cur). Methods: Cur-NCs with different drug-carrier ratios were prepared by one-step extrusion process with Eudragit® EPO (EEP) as the carrier. The dispersed size and solid state of Cur in extruded samples were characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The thermal stability of Cur was analyzed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC). Dissolution and pharmacokinetics were studied to evaluate the improvement of dissolution and absorption of Cur by nano-preparation. Results: Cur-NCs with particle sizes in the range of 50~150 nm were successfully prepared by using drug-carrier ratios of 1:1, 2:1 and 4:1, and the crystal form of Cur was Form 1 both before and after HME. The extrudate powders showed very efficient dissolution with the cumulative dissolution percentage of 80% in less than 2 min, and the intrinsic dissolution rates of them were 13.68 ± 1.20 mg/min/cm2, 11.78 ± 0.57 mg/min/cm2 and 4.35 ± 0.20 mg/min/cm2, respectively, whereas that of pure Cur was only 0.04 ± 0.00 mg/min/cm2. The TGA data demonstrated that the degradation temperature of Cur was about 250 °C, while the HPLC results showed Cur was degraded when extruded at the temperature over 150 °C. Pharmacokinetic experiment showed a significant improvement in the absorption of Cur. The Cmax of Cur in the Cur-NC group was 1.68 times that of pure Cur group, and the Cmax and area under the curve (AUC0-∞) of metabolites were 2.79 and 4.07 times compared with pure Cur group. Conclusion: Cur-NCs can be prepared by HME technology in one step, which significantly improves the dissolution and bioavailability of Cur. Such a novel method for preparing insoluble drug nanocrystals has broad application prospects.


Assuntos
Disponibilidade Biológica , Curcumina , Tecnologia de Extrusão por Fusão a Quente , Nanopartículas , Tamanho da Partícula , Solubilidade , Curcumina/farmacocinética , Curcumina/química , Curcumina/administração & dosagem , Nanopartículas/química , Animais , Tecnologia de Extrusão por Fusão a Quente/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Masculino , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Liberação Controlada de Fármacos , Difração de Raios X , Ácidos Polimetacrílicos
14.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892468

RESUMO

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin's biological activities is limited in most aqueous experimental systems. In the present study, the effects of polyvinyl alcohol (PVA), a dietary-compatible vehicle, on the solubility, stability, cellular uptake, and bioactivities of curcumin were investigated. Curcumin solubility was improved significantly by PVA; the color intensity of curcumin aqueous solution in the presence of PVA increased concentration-dependently with its peak shift to a shorter wavelength. Improved suspension stability and photostability of curcumin in an aqueous solution were also observed in the presence of PVA, even at 62.5 µg/mL. The scavenging activities of curcumin against DPPH, ABTS, AAPH radicals, and nitric oxide were enhanced significantly in the presence of PVA. PVA at 250 µg/mL also significantly enhanced the cytotoxic activity of curcumin against both HCT 116 colon cancer and INT 407 (HeLa-derived) embryonic intestinal cells by reducing the IC50 from 16 to 11 µM and 25 to 15 µM, respectively. PVA improved the cellular uptake of curcumin in a concentration-dependent manner in INT 407 cells; it increased the cellular levels more effectively at lower curcumin treatment concentrations. The present results indicate that PVA improves the solubility and stability of curcumin, and changes in these chemical behaviors of curcumin in aqueous systems by PVA could enhance the bioavailability and pharmacological efficacy of curcumin.


Assuntos
Curcumina , Álcool de Polivinil , Solubilidade , Curcumina/farmacologia , Curcumina/química , Álcool de Polivinil/química , Humanos , Estabilidade de Medicamentos , Células HCT116 , Células HeLa , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sobrevivência Celular/efeitos dos fármacos
15.
Food Res Int ; 189: 114536, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876589

RESUMO

Walnut isolate protein (WPI)-epigallocatechin gallate (EGCG) conjugates can be employed to creat food-grade delivery systems for preserving bioactive compounds. In this study, WPI-EGCG nanoparticles (WENPs) were developed for encapsulating lycopene (LYC) using the ultrasound-assisted method. The results indicated successful loading of LYC into these WENPs, forming the WENPs/LYC (cylinder with 200-300 nm in length and 14.81-30.05 nm in diameter). Encapsulating LYC in WENPs led to a notable decrease in release rate and improved stability in terms of thermal, ultraviolet (UV), and storage conditions compared to free LYC. Simultaneously, WENPs/LYC exhibited a synergistic and significantly higher antioxidant activity with an EC50 value of 23.98 µg/mL in HepG2 cells compared to free LYC's 31.54 µg/mL. Treatment with WENPs/LYC led to a dose-dependent restoration of intracellular antioxidant enzyme activities (SOD, CAT, and GSH-Px) and inhibition of intracellular malondialdehyde (MDA) formation. Furthermore, transcriptome analysis indicated that enrichment in glutathione metabolism and peroxisome processes following WENPs/LYC addition. Quantitative real-time reverse transcription PCR (qRT-PCR) verified the expression levels of related genes involved in the antioxidant resistance pathway of WENPs/LYC on AAPH-induced oxidative stress. This study offers novel perspectives into the antioxidant resistance pathway of WENPs/LYC, holding significant potential in food industry.


Assuntos
Antioxidantes , Catequina , Juglans , Licopeno , Nanopartículas , Licopeno/farmacologia , Licopeno/química , Antioxidantes/farmacologia , Antioxidantes/química , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/química , Juglans/química , Humanos , Nanopartículas/química , Células Hep G2 , Proteínas de Plantas , Malondialdeído/metabolismo , Estabilidade de Medicamentos , Superóxido Dismutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos
16.
J Pharm Biomed Anal ; 246: 116214, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38781727

RESUMO

Clorsulon is an effective anthelmintic drug substance extensively used in the treatment of parasitic infestations in both cattle and sheep. An in-depth investigation of Clorsulon's degradation products (DPs) was carried out through forced degradation study to comprehend its degradation path. A total of eight degradation products were separated under various stress degradation conditions. Structural elucidation of these DPs was conducted using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), and their fragmentation patterns were compared to that of the parent compound. Adequate amount of DP-4 was isolated and purified by semi-preparative high-performance liquid chromatography (HPLC) methods. Subsequently, it was examined in detail using both 1D and 2D NMR (nuclear magnetic resonance spectroscopy). Most probable mechanistic pathways for the formation of degradation products under various stress degradation conditions were proposed to better understand the degradation profile. Based on the results of the stress study, Clorsulon drug substance was found to be unstable under photolytic and oxidative conditions. Understanding Clorsulon's degradation pathway is essential for determining shelf-life prediction of the finished product, safety and efficacy assurance, and guiding the development of stable, high-quality formulations.


Assuntos
Anti-Helmínticos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Anti-Helmínticos/análise , Anti-Helmínticos/química , Espectrometria de Massas/métodos , Oxirredução , Fotólise
17.
J Pharm Biomed Anal ; 246: 116201, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788621

RESUMO

Patient can be exposed to the photodegradation products of a drug after skin application of topical formulations. NSAIDs, with analgesic and anti-inflammatory properties, are known for the potential photoinstability, and are applied often in the form of creams, gels or liquids, commonly used among athletes, elderly people, geriatric patients and patients treated with multidrug therapies. Susceptibility to photodegradation hazard of those group arises the need for development of a new approach, with the ability to evaluate the patient safety. We planned to use a rapid assessment procedure (RAP) of safety by testing the photostability of popular skin medicinal products. This method, proposed many years ago by WHO, is now reintroduced to analytical applications in industry, when emergency drugs (e.g. for Covid) are implemented to the market in accelerated procedures. In the health care system, qualitative evaluation of drugs is extremely valuable, therefore we have planned to identify photodegradation using the FTIR method - infrared spectroscopy and DSC - differential scanning calorimetry, whilst the risk of formation of genotoxic products using the Ames test. We have successfully demonstrated that changes in the chemical structure and physical form of both pure APIs and drug products containing the API be assessed in a short time. Another advantage of our work is the combination of the developed results from FTIR/NIR spectra with statistical analysis. As a result, full and quick qualitative assessment of the effects of photoexposure of selected NSAIDs is performed, fortunately showing no mutagenicity. Due to the popularity of NSAIDs applied to the skin, a gel containing naproxen and spray with indomethacin were selected for testing. The analysis carried out for various formulations of both preparations allows us to demonstrate the universality of the applied RAP methods in assessing the risk of hazard to the patient, thus we present research results that expand or widen the knowledge and assessment of risks related to the use of drugs on the skin.


Assuntos
Anti-Inflamatórios não Esteroides , Indometacina , Naproxeno , Fotólise , Pele , Anti-Inflamatórios não Esteroides/química , Naproxeno/química , Naproxeno/análise , Indometacina/química , Humanos , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Varredura Diferencial de Calorimetria/métodos , Administração Cutânea , Estabilidade de Medicamentos
18.
Int J Biol Macromol ; 271(Pt 2): 132336, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744371

RESUMO

The current study entails the encapsulation validity to enclose naturally occurring food preservatives, such as cinnamon essential oil (CM), within various wall materials. This approach has demonstrated enhanced encapsulated compounds' stability, efficiency, and bioactivity. The base carrier system consisted of a solid lipid (Berry wax, RW) individually blended with whey protein (WYN), maltodextrin (MDN), and gum Arabic (GMC) as wall materials. The resulting formulations were freeze-dried: WYN/RW/CM, MDN/RW/CM, and GMC/RW/CM. The study comprehensively analyzed encapsulation efficiency, morphology, crystallinity, thermal, and physiochemical properties. When RW was combined with WYN, MDN, and GMC, the microcapsule WYN/RW/CM showed the highest efficiency at 93.4 %, while the GMC/RW/CM exhibited the highest relative crystallinity at 46.54 %. Furthermore, the investigation assessed storage stability, release of bioactive compounds, and oxidative stability during storage at 4 °C/ 25 % RH ± 5 % and 25 °C/40 % RH ± 5 % for 55 days, revealing optimal stability in the WYN/RW/CM microcapsule. Additionally, the antimicrobial activity was assessed at various concentrations of microcapsules, revealing their inhibitory effect against Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) bacteria. The WYN/RW/CM microcapsule exhibited the highest inhibition activity in both strains, reaching 40 mm. This study demonstrates that combining WYN with RW as a wall material has greater efficiency in encapsulation and potential uses in various industrial sectors.


Assuntos
Antioxidantes , Cápsulas , Cinnamomum zeylanicum , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Cinnamomum zeylanicum/química , Biopolímeros/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Goma Arábica/química , Estabilidade de Medicamentos , Polissacarídeos/química , Polissacarídeos/farmacologia , Proteínas do Soro do Leite/química , Fenômenos Químicos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana
19.
Ultrason Sonochem ; 107: 106892, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761772

RESUMO

Litsea cubeba essential oil (LCEO) has garnered widespread attention due to its robust biological activity. However, challenges such as high volatility, limited water solubility, and low bioavailability impede its application. Nano-emulsion encapsulation technology offers an effective solution to these issues. In this study, we prepared litsea cubeba essential oil nano-emulsion (LCEO-NE) for the first time using whey protein (WP) as the emulsifier through an ultrasonic-assisted method, achieving high efficiency with minimal energy consumption. Transmission electron microscopy and dynamic light scattering analyses revealed that the nanoparticles were uniformly spherical, with a particle size of 183.5 ± 1.19 nm and a zeta potential of -35.5 ± 0.95 mV. Stability studies revealed that LCEO-NE exhibited excellent thermal and salt stability, maintaining its integrity for up to four weeks when stored at 4 °C and 25 °C. In vitro digestion assays confirmed the digestibility of LCEO-NE. Furthermore, evaluation of the DPPH, ABTS, and antimicrobial activities revealed that LCEO-NE displayed superior bacteriostatic and antioxidant properties compared to LCEO. Scanning electron microscopy elucidated that its bacteriostatic effect involved the disruption of bacterial microstructure. Hemocompatibility and cytotoxicity assays demonstrated the safety of LCEO-NE within the effective concentration range. This research supports the utilization of nanoparticles for encapsulating LCEO, thereby enhancing its stability and bioactivity, and consequently expanding its applications in the food and pharmaceutical industries.


Assuntos
Emulsões , Litsea , Óleos Voláteis , Proteínas do Soro do Leite , Litsea/química , Proteínas do Soro do Leite/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/toxicidade , Antioxidantes/farmacologia , Antioxidantes/química , Sonicação , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/toxicidade , Tamanho da Partícula , Estabilidade de Medicamentos , Humanos
20.
Biomed Chromatogr ; 38(7): e5892, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38769722

RESUMO

A simple and sensitive LC-tandem mass spectrometry method was established and validated for the determination of schaftoside in rat plasma. After prepared by protein precipitation with acetonitrile, schaftoside and internal standard were separated on a Waters HSS T3 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as the mobile phase by gradient elution. The method showed excellent linearity over the range of 0.5-500 ng/mL with acceptable intra- and inter-day precision, accuracy, matrix effect, and recovery. The stability assay indicated that schaftoside was stable during the sample acquisition, preparation, and storage. The method was applied to a pharmacokinetic study of schaftoside in rats. The result suggested that after intravenous administration at a dose of 1 mg/kg, schaftoside was quickly eliminated from the plasma with an elimination half-life of 0.58 h. After oral administration at doses of 5, 10, and 20 mg/kg, schaftoside was quickly absorbed into the plasma and reached the peak concentration (Cmax) of 45.1-104.99 ng/mL at 0.67-1.17 h. The increase of exposure (area under the curve) was linear with the increase of dose. The oral bioavailability was 0.42%-0.71% in the range of 5-20 mg/kg.


Assuntos
Disponibilidade Biológica , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Ratos , Masculino , Administração Oral , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Modelos Lineares , Cromatografia Líquida/métodos , Limite de Detecção , Sensibilidade e Especificidade , Glicosídeos/farmacocinética , Glicosídeos/sangue , Glicosídeos/química , Estabilidade de Medicamentos
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