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OBJECTIVE: In the current research, 6-gingerol (GA)-loaded nanofiber drug delivery system were developed, and their potential usage in wound healing was evaluated. SIGNIFICANCE: This study investigates the effectiveness of nanofibrous membranes composed of sodium alginate (SA), poly(vinyl alcohol) (PVA), and 6-gingerol (GA) as delivery systems for anti-inflammatory agents in the context of wound dressings. METHODS: GA-loaded SA/PVA nanofiber was prepared using electrospinning. In vitro characterization of this nanofiber included the examination of comprehensive in vitro characterization, anti-inflammatory and antioxidant activities, cytotoxicity, a scratch tes and in vivo skin test. RESULTS: GA was extracted from Zingiber officinale, and its successful isolation was confirmed through analyses such as H-NMR, C-NMR. Then GA was electrospuned into the SA/PVA nanofibers, and scanning electron microscopy (SEM) imaging revealed that the fiber diameters of the formulations ranged between 148 nm and 176 nm. Anti-inflammatory and antioxidant studies demonstrated that the effectiveness of GA increased with higher doses; however, this increase was accompanied by decreased cell viability. In vitro release studies revealed that GA exhibited a burst release within the first 8 h, followed by a controlled release, reaching completion within 24 h. Within the scope of in vitro release kinetics, release data are mathematically compatible with the Weibull model with high correlation. The scratch test results indicated that TB2 (%1 GA) promoted epithelialization. Furthermore, it was determined that TB2 (%1 GA) did not cause any irritation. CONCLUSIONS: As a result, TB2 shows promise as a formulation for wound dressings, offering potential benefits in the field of wound care.
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Alginatos , Antioxidantes , Catecoles , Alcoholes Grasos , Nanofibras , Alcohol Polivinílico , Cicatrización de Heridas , Alcoholes Grasos/química , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Catecoles/química , Catecoles/farmacología , Catecoles/administración & dosificación , Alginatos/química , Animales , Alcohol Polivinílico/química , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos , Zingiber officinale/química , Sistemas de Liberación de Medicamentos/métodos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Vendajes , Ratas , Polímeros/química , Masculino , RatonesRESUMEN
Inhaled colistin is used to treat pneumonia and respiratory infections through nebulization or dry powder inhalers. Nevertheless, the development of a metered-dose inhaler (MDI) for colistin, which could enhance patient convenience and treatment efficacy, has not yet been developed. Colistin is known for its ability to induce cellular toxicity. Gold nanoparticles (AuNPs) can potentially mitigate colistin toxicity. Therefore, this study aimed to evaluate the antimicrobial effectiveness of colistin conjugated with chitosan-capped gold nanoparticles (Col-CS-AuNPs) and their potential formulation for use with MDIs to deliver the aerosol directly to the deep lung. Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and elemental analysis were used to characterize the synthesized Col-CS-AuNPs. Drug release profiles fitted with the most suitable release kinetic model were evaluated. An MDI formulation containing 100 µg of colistin per puff was prepared. The aerosol properties used to determine the MDI performance included the fine particle fraction, mass median aerodynamic diameter, and geometric standard deviation, which were evaluated using the Andersen Cascade Impactor. The delivered dose uniformity was also determined. The antimicrobial efficacy of the Col-CS-AuNP formulation in the MDI was assessed. The chitosan-capped gold nanoparticles (CS-AuNPs) and Col-CS-AuNPs had particle sizes of 44.34 ± 1.02 and 174.50 ± 4.46 nm, respectively. CS-AuNPs effectively entrapped 76.4% of colistin. Col-CS-AuNPs exhibited an initial burst release of up to 60% colistin within the first 6 h. The release mechanism was accurately described by the Korsmeyer-Peppas model, with an R2 > 0.95. The aerosol properties of the Col-CS-AuNP formulation in the MDI revealed a high fine particle fraction of 61.08%, mass median aerodynamic diameter of 2.34 µm, and geometric standard deviation of 0.21, with a delivered dose uniformity within 75-125% of the labeled claim. The Col-CS-AuNP MDI formulation completely killed Escherichia coli at 5× and 10× minimum inhibitory concentrations after 6 and 12 h of incubation, respectively. The toxicity of CS-AuNP and Col-CS-AuNP MDI formulations in upper and lower respiratory tract cell lines was lower than that of free colistin. The stability of the Col-CS-AuNP MDI formulation was maintained for at least 3 months. The Col-CS-AuNP MDI formulation effectively eradicated bacteria over a 12-h period, showing promise for advancing lung infection treatments.
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Researchers continuously focused on the fabrication of innovative drug delivery systems to prevent microbial infections while minimizing systemic side effects. Among these, pH-sensitive antibiotic release systems based on bio-based materials have gained great attention due to their ability to precisely modulate drug kinetics and enhance therapeutic efficacy. Herein, pH-sensitive alginate/hyaluronic acid/gelatin ternary blended films were fabricated for the controlled release of ampicillin. Swelling capacity, hydrolytic degradation profile, pH reversibility and in vitro ampicillin release behavior of produced films were investigated in both simulated gastric (pH 1.2) and intestinal (pH 7.4) environments. The cumulative release amount of ampicillin at pH 1.2 (61.0 ± 1.07 mg drug/g polymer) was greater than that of at pH 7.4 (43.0 ± 1.05 mg drug/g polymer) proved that release behavior of ampicillin for produced films is pH-dependent. Based on the fitted release data, best fit was found as the first-order kinetic model with the highest R2 values of 0.966 and 0.962 for both pH conditions. According to Korsmeyer-Peppas model, drug release mechanism is also controlled by case II-transport. Furthermore, produced films demonstrated excellent cytocompatibility. All results revealed that obtained films could be a promising drug carrier to traditional targeting systems for site-specific, pH-sensitive ampicillin delivery in both gastric and intestine.
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Alginatos , Ampicilina , Portadores de Fármacos , Liberación de Fármacos , Gelatina , Ácido Hialurónico , Ampicilina/química , Ampicilina/farmacología , Ácido Hialurónico/química , Concentración de Iones de Hidrógeno , Gelatina/química , Portadores de Fármacos/química , Cinética , Alginatos/química , Antibacterianos/química , Antibacterianos/farmacología , AnimalesRESUMEN
During the COVID-19 pandemic, a substantial quantity of disposable face masks was discarded, consisting of three layers of nonwoven fabric. However, their improper disposal led to the release of microplastics (MPs) and nanoplastics (NPs) when they ended up in aquatic environments. To analyze the release kinetics and size characteristics of these masks, release experiments were performed on commercially available disposable masks over a period of 7 days and micro- and nanoplastic releases were detected using fiber counting and nanoparticle tracking analysis. The study's findings revealed that there was no significant difference (p > 0.05) in the quantity of MPs released among the layers of the masks. However, the quantity of NPs released from the middle layer of the mask was 25.9 ± 1.3 × 108 to 81.3 ± 5.3 × 108 particles/piece, significantly higher than the inner and outer layers (p < 0.05). The release process of micro/nanoplastics (M/NPs) from each layer of the mask followed the Elovich equation and the power function equation, indicating that the release was divided into two stages. MPs in the range of 1-500 µm and NPs in the range of 100-300 nm dominated the release from each layer of the mask, accounting for an average of 93.81% and 67.52%, respectively. Based on these findings, recommendations are proposed to reduce the release of M/NPs from masks during subsequent use.
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COVID-19 , Máscaras , Microplásticos , Plásticos , Microplásticos/análisis , COVID-19/prevención & control , Humanos , Contaminantes Químicos del Agua/análisis , SARS-CoV-2 , Nanopartículas/químicaRESUMEN
This study aimed to develop new generation cakes that were fortified with calcined ZnO nanoparticles (CZnO), uncalcined ZnO nanoparticles (UCZnO), beads (B(CZnO)) synthesized by encapsulating the CZnO with sodium alginate (SA), and the beads (B(UCZnO)) synthesized by encapsulating the UCZnO with sodium alginate (SA) and investigated the zinc (Zn) release in fortified cakes in simulated body fluids (SBF). The present study represents a novel method for increasing intestinal absorption and bioavailability of dietary zinc with zinc nanoparticles for use in the preparation of Zn fortified cakes as a dietary supplement to compensate for zinc deficiency in humans. The results revealed that a rapid increase in the release time and rate in the SGF solution was noted in the UCZnO added cakes. It was attributed to increased intestinal absorption and bioavailability as a result of the ultra-small size of ZnO. Also, ZnO release kinetics in SBF was also studied and data were adjusted into different kinetic models involving zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. The present investigation recommends adding UCZnO to the cakes to control and increase the release from the cakes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05840-x.
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Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91-4.92%) on days 2-3. On days 5-7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.
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The kinetic release of phenolic compounds from biodegradable films with Clitoria ternatea flower extract (ECT) in different food-simulant fluids and compostability were evaluated for the first time. This work aimed to incorporate ECT in starch-PVA-based film formulations, and the antioxidant capacity, total phenolic compounds, opacity, color, mechanical properties, compostability, and polyphenol release in different fluid simulants were determined. The results obtained showed that antioxidant activity and the total phenolic compounds were ECT dose dependent. Due to its antioxidant properties, ECT interfered with the film's composting process, reaching an average weight loss of 70 %. Additionally, the addition of ECT interfered with the mechanical properties, reducing the tensile strength, probably due to the plasticizer effect. The type of simulating fluid influenced the release of polyphenols from the films, and the presence of water favored the release because it hydrated and swelled the starch-PVA matrix, facilitating diffusion. The classic zero- and first-order models were the most effective in describing the release kinetics of polyphenols from the films. The results of this study demonstrate that the antioxidant potential and the release of polyphenols from starch-PVA-based films in different simulated fluids allow their application in active packaging, making them a sustainable alternative for food preservation.
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Antioxidantes , Clitoria , Antioxidantes/farmacología , Almidón , Fenoles , Polifenoles , Flores , Embalaje de AlimentosRESUMEN
Psoriasis is a chronic disorder that causes a rash with itchy, scaly patches. It affects nearly 2-5% of the worldwide population and has a negative effect on patient quality of life. A variety of therapeutic approaches, e.g., glucocorticoid topical therapy, have shown limited efficacy with systemic adverse reactions. Therefore, novel therapeutic agents and physicochemical formulations are in constant need and should be obtained and tested in terms of effectiveness and minimization of side effects. For that reason, the aim of our study was to design and obtain various hybrid systems, nanoemulgel-macroemulsion and nanoemulgel-oleogel (bigel), as vehicles for ursolic acid (UA) and to verify their potential as topical formulations used in psoriasis treatment. Obtained topical formulations were characterized by conducting morphological, rheological, texture, and stability analysis. To determine the safety and effectiveness of the prepared ursolic acid carriers, in vitro studies on human keratinocyte cell-like HaCaT cells were performed with cytotoxicity analysis for individual components and each formulation. Moreover, a kinetic study of ursolic acid release from the obtained systems was conducted. All of the studied UA-loaded systems were well tolerated by keratinocyte cells and had suitable pH values and stability over time. The obtained formulations exhibit an apparent viscosity, ensuring the appropriate time of contact with the skin, ease of spreading, soft consistency, and adherence to the skin, which was confirmed by texture tests. The release of ursolic acid from each of the formulations is followed by a slow, controlled release according to the Korsmeyer-Peppas and Higuchi models. The elaborated systems could be considered suitable vehicles to deliver triterpene to psoriatic skin.
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OBJECTIVE: In the current research, lornoxicam-loaded in situ gels were developed, and their potential usage in ocular inflammation was evaluated. SIGNIFICANCE: Lornoxicam cyclodextrin complex prepared with hydroxypropyl methylcellulose and poloxamer P407 because of the low viscosity of in situ gels to provide easy application. However, washing and removing it from the ocular surface becomes difficult due to the gelation formation with heat. METHODS: A three-level factorial experimental design was used to evaluate the effects of poloxamer 407 concentration, polymer type, and polymer concentration on viscosity, pH, gelation capacity, gelation time, and gelation temperature, which were considered the optimal indicators of lornoxicam-containing formulations. RESULTS: As a result of the three-level factorial experimental design, the optimized formulation contained 15 (%w/v) poloxamer 407 and 1 (%w/v) hydroxypropyl methylcellulose. The optimize formulation viscosity 25 °C = 504 ± 49cP, viscosity 35 °C = 11247 ± 214cP, pH = 6.80 ± 0.01, gelation temprature = 35 ± 0.2 °C, and gelation time= 34 ± 0.2 s was obtained. In the in vitro release studies, 68% of lornoxicam was released with a burst effect in the first three hours; then, the release continued for eight hours with controlled release. Release kinetics of the formulations were modeled mathematically, and it was found to be compatible with the Korsemeyer-Peppas and Weibull models. In cell culture studies, cell viability at 100 µg/mL was 83% and 96% for NL6 and NL6-CD, respectively. In Draize's in vivo test, no negative conditions occurred in rats. CONCLUSIONS: Therefore, the NL6-CD formulation has the potential to be a favorable option for treating ocular inflammation.
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Calor , Poloxámero , Ratas , Animales , Derivados de la Hipromelosa , Proyectos de Investigación , Geles , Temperatura , Inflamación , ViscosidadRESUMEN
Vascular graft infections are a severe complication in vascular surgery, with a high morbidity and mortality. Prevention and treatment involve the use of antibiotic- or antiseptic-impregnated artificial vascular grafts, but currently, there are no commercially available infection-proof small-diameter vascular grafts (SDVGs). In this work we investigated the antimicrobic activity of two SDVGs prototypes loaded with tobramycin and produced via the electrospinning of drug-doped PLGA (polylactide-co-glycolide) solutions. Differences in rheological and conductivity properties of the polymer solutions resulted in non-identical fibre morphology that deeply influenced the hydration profile and consequently the in vitro cumulative drug release, which was investigated by using a spectrofluorimetric technique. Using DDSolver Excel add-in, modelling of the drug release kinetic was performed to evaluate the release mechanism involved: Prototype 1 showed a sustained and diffusive driven drug release, which allowed for the complete elution of tobramycin within 2 weeks, whereas Prototype 2 resulted in a more extended drug release controlled by both diffusion and matrix relaxation. Time-kill assays performed on S. aureus and E. coli highlighted the influence of burst drug release on the decay rate of bacterial populations, with Prototype 1 being more efficient on both microorganisms. Nevertheless, both prototypes showed good antimicrobic activity over the 5 days of in vitro testing.
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Globally, more than 6 million metric tons of agricultural plastic films are used to increase crop yields and reduce the use of water and herbicides, resulting in the contamination of soil and water by plastic debris and additives. However, knowledge of the occurrence and release of additives from agricultural films is limited. In this study, suspect screening with high-resolution mass spectrometry, one-dimensional Fickian diffusion models, and linear free energy relationships (LFERs) were used to determine the occurrence and mass transfer of various additives from agricultural plastic films. A total of 89 additives were tentatively identified in 40 films, and 62 of them were further validated and quantified. The aqueous concentrations of 26 released additives reached mg L-1 after a 28 day incubation at 25 °C. Diffusion models and LFERs demonstrated that the film-water partition coefficient and the diffusivity in the polymer, the two critical parameters controlling the mass transfer, could be predicted using Abraham descriptors. The findings of this study highlighted the need for future research on the environmental fate and risk assessment of previously neglected additives in agricultural plastic films and other similar products.
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Plásticos , Agua , Plásticos/análisis , Agricultura , Polímeros , SueloRESUMEN
Masks-related microplastic pollution poses a new threat to the environment and human health that has gained increasing concern. However, the long-term release kinetics of microplastic from masks in aquatic environments have yet to studied, which hampers its risk assessment. Four types of masks, namely cotton mask, fashion mask, N95 mask, and disposable surgical mask were exposed to systematically simulated natural water environments to determine the time-dependent microplastic release characteristics at 3, 6, 9, and 12 months, respectively. In addition, the structure changes of employed masks were examined by scanning electron microscopy. Moreover, Fourier transform infrared spectroscopy was applied to analyze the chemical composition and groups of released microplastic fibers. Our results showed that the simulated natural water environment could degrade four types of masks and continuously produce microplastic fibers/fragments in a time-dependent manner. The dominant size of released particles/fibers was below 20 µm across four types of face masks. The physical structure of all four masks was damaged to varying degrees concomitant with photo-oxidation reaction. Collectively, we characterized the long-term release kinetics of microplastic from four types of commonly used masks under a well-mimic real word water environment. Our findings suggest that urgent action must be taken to properly manage disposable masks and ultimately limit the health threats associated with discarded masks.
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Microplásticos , Contaminantes Químicos del Agua , Humanos , Plásticos , Agua , Cinética , Ambiente , Contaminantes Químicos del Agua/análisisRESUMEN
This work aims to develop an injectable and antibacterial composite cement for bone substitution and prevention/treatment of bone infections. This cement is composed of calcium phosphate, calcium carbonate, bioactive glass, sodium alginate, and ciprofloxacin. The effect of ciprofloxacin on the microstructure, chemical composition, setting properties, cohesion, injectability, and compressive strength was investigated. The in vitro drug release kinetics and the antibacterial activity of ciprofloxacin-loaded composites against staphylococcus aureus and Escherichia coli pathogens were investigated. XRD and FTIR analysis demonstrated that the formulated cements are composed of a nanocrystalline carbonated apatite analogous to the mineral part of the bone. The evaluation of the composite cement's properties revealed that the incorporation of 3 and 9 wt% of ciprofloxacin affects the microstructural and physicochemical properties of the cement, resulting in a prolonged setting time, and a slight decrease in injectability and compressive strength. The in vitro drug release study revealed sustained release profiles over 18 days. The amounts of ciprofloxacin released per day (0.2 -15.2 mg/L) depend on the cement composition and the amount of ciprofloxacin incorporated. The antibacterial activity of ciprofloxacin-loaded cement composites attested to their effectiveness to inhibit the growth of Staphylococcus aureus and Escherichia coli.
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Ciprofloxacina , Infecciones Estafilocócicas , Humanos , Ciprofloxacina/farmacología , Cinética , Antibacterianos/farmacología , Antibacterianos/química , Apatitas/química , Apatitas/farmacología , Fosfatos de Calcio/farmacología , Staphylococcus aureus , Escherichia coli , Cementos para Huesos/farmacología , Cementos para Huesos/químicaRESUMEN
PURPOSE: Development of multifunctional advanced stent implants (metal/polymer composite)-drug-eluting stents with superior material and optical properties is still a challenge. In this research work, multifunctional metal-polymer composite drug-eluting substrates (DES) for stent application were developed by using commercially pure titanium (cpTi) and polyethylene glycol (PEG). METHODS: Surface modifications on titanium substrates were carried out by sodium hydroxide under various concentrations; 5M (6 and 24 h) and 10M (6 and 24 h). It induces a nanoporous structure which facilitates the larger area for encapsulation of the drug, Aspirin (ASA) via intermolecular forces followed by polymer coating of PEG (MW-20,000) by physical adsorption process, which is structured as layer-by-layer gathering. RESULTS: The developed cpTi-PEG DES were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), optical energy bandgap, static contact angle measurement, antithrombotic and drug release studies. The development of sodium titanate oxide prompted surface nano-features revealed by SEM and XRD. Moreover, FTIR confirms the presence of ASA and PEG functional groups over the cpTi surface. Drug release studies fitted with Ritger-Peppas kinetic model (≤ 60%), which indicates the super case II transport mechanisms (n > 1). Further UV-visible absorbance spectrum was quantified by the Tauc plot, which shows the broadening of the energy bandgap (Eg). In addition, the shrink in blood clots was more around the Tib2/ASA/PEG.Please confirm the inserted city name in affiliations [1,2] are correct and amend if necessary.Yes, city name "Rourkela" is correct. CONCLUSION: Developed cpTi-PEG DES has improved optical properties and prevent thrombus formation which suggesting it a potential substrate to overcome prime clinical challenges.
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Polietilenglicoles , Titanio , Titanio/química , Fibrinolíticos , Polímeros , Stents , Metales , AspirinaRESUMEN
Emulsion is a colloidal dispersion for delivering natural antimicrobial, antioxidant, and bioactive compounds to improve the product's quality. The present study aimed to develop the active emulsion film based on whey protein isolate (WPI) by adding oleic acid (OA) (0, 10, and 20% w/w) and green tea extract (GTE) (0 and 0.5% w/v) for cheese packaging. Results showed that the opacity, flexibility, and water barrier properties of WPI hydrogel-based film were significantly increased by adding 10% OA. Active release from emulsion-based films was governed by pH and the nature of food model systems. The minimum release occurred in the acidic food model system. After 5â h exposure in the acid food model system, the obtained release from the active film containing OA 0, 10, and 20% was 52.39, 48.97, and 57.24% of incorporated GTE, respectively. The log reduction value (LRV) of active emulsion film against bacteria was significantly affected by the food model system. Moreover, packed lactic coagulated cheese delivered more phenolic compound of GTE than processed spread cheese. Korsmeyer-Peppas model and Weibull with lag were suggested as appropriate models to forecast the release kinetic of GTE.
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Queso , Ácido Oléico , Proteína de Suero de Leche/química , Embalaje de Alimentos/métodos , Emulsiones , Antioxidantes/químicaRESUMEN
"Boba balls" or pearls have recently gained popularity for beverages or food toppings. "Boba balls" could be developed into functional foods by the encapsulation of bioactive compounds. In this study, gelatin/sodium alginate composite "Boba balls" enriched with pomegranate peel extract (PPE) at different concentrations (0, 1, 2, and 3%) were prepared. They were characterized in terms of physical, rheological, textural, morphological, and sensory properties, as well as in vitro digestion, bio-accessibility, and release kinetic of PPE. Adding PPE improved the "Boba" mix's viscoelasticity and decreased the "Boba balls"' hardness. The increasing PPE ratio significantly (p < 0.05) increased the antioxidant capacity and total phenolic content. The addition of PPE preserved the spherical shape of the "Boba balls", and as the PPE ratio increased, new junction zones were observed in SEM images. The in vitro digestibility of PPE was significantly (p < 0.05) improved by preserving PPE from the mouth and gastric medium, and "Boba balls" showed the highest release and bio-accessibility in the intestinal medium. Consequently, PPE as a by-product could be successfully used at 2% concentration for enhancing the functionality and bio-accessibility of "Boba balls" without affecting sensory properties.
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Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood-brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.
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On demand production of totally customizable combinative preparations is a central goal of a patient-centric pharmaceutical supply chain. Additive manufacturing techniques like fused deposition modeling (FDM) could be key technologies towards such individualized dosage forms. As so far only a limited number of studies on 3D printed combinative preparations applying FDM have been reported, a core-shell dosage form was the focus of the present study. Dosage forms with an initial and a sustained release part with theophylline as model API were successfully produced applying a dual nozzle FDM 3D printer. Investigations identified microstructural defects at the interface between the two formulations by means of µCT analysis. Dissolution testing proved the achievement of the intended release profile. In combination with additionally characterized release profile of single material prints of different shapes, the combinative release profiles could be predicted by developing model equations and taking into account the geometric composition. As these model approaches can accordingly facilitate the prediction of API release from 3D printed combinative preparations with only data from single material release. This is a first step towards a truly individualized and reliable patient-centric pharmaceutical supply via 3D printing.
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Impresión Tridimensional , Tecnología Farmacéutica , Formas de Dosificación , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Cinética , Preparaciones Farmacéuticas , Comprimidos/química , Tecnología Farmacéutica/métodosRESUMEN
In this work, films containing AgNPs were obtained by different green synthesis techniques (AgNP in situ and AgNP L). The inclusion of nanoparticles in the starch matrix improved both mechanical and barrier properties. The migration of AgNPs from the nanocomposite material to three food simulants (water, 3% v/v acetic acid and 15% v/v ethanol) was studied. The experimental data were fitted by using different widely accepted mathematical models (Fickian, Ritger and Peppas, and Weibull), indicating that the AgNP migration followed a complex mechanism. The silver concentration (mg Ag per kg of simulant) that was released from the nanocomposite films was higher for the samples with AgNPs in situ than for those containing AgNP L. Likewise, the maximum release value (0.141 mg/dm2 for AgNPs in situ in acetic acid simulant) was lower than the limits proposed by the legislation (European Commission and MERCOSUR; 10 and 8 mg/dm2, respectively). The replacement of conventional plastic materials by biodegradable ones requires the evaluation of bio-disintegration tests in soil. In this sense, a period of 90 days was necessary to obtain ≥50% weight loss in both nanocomposite films. Additionally, the bio-disintegration of the samples did not contribute with phytotoxic compounds to the soil, allowing the germination of fast-growing seeds.
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Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.