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1.
AAPS PharmSciTech ; 25(6): 144, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918282

RESUMEN

The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.


Asunto(s)
Quitosano , Dexametasona , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Geles , Micelas , Poloxámero , Dexametasona/administración & dosificación , Dexametasona/química , Quitosano/química , Geles/química , Sistemas de Liberación de Medicamentos/métodos , Poloxámero/química , Tensoactivos/química , Química Farmacéutica/métodos , Hidrogeles/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Nanopartículas/química , Portadores de Fármacos/química , Reología/métodos , Úlceras Bucales/tratamiento farmacológico , Administración Oral , Lípidos/química , Ácido Oléico/química
2.
AAPS PharmSciTech ; 25(7): 208, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237678

RESUMEN

Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R2), adjusted R2, the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R2 values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R2 values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors.


Asunto(s)
Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Lípidos , Liposomas , Nanopartículas , Nanopartículas/química , Lípidos/química , Liposomas/química , Sistemas de Liberación de Medicamentos/métodos , Modelos Teóricos , Portadores de Fármacos/química , Emulsiones/química , Química Farmacéutica/métodos
3.
Mol Pharm ; 20(8): 3757-3778, 2023 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-37428824

RESUMEN

Cell-based drug delivery systems are new strategies in targeted delivery in which cells or cell-membrane-derived systems are used as carriers and release their cargo in a controlled manner. Recently, great attention has been directed to cells as carrier systems for treating several diseases. There are various challenges in the development of cell-based drug delivery systems. The prediction of the properties of these platforms is a prerequisite step in their development to reduce undesirable effects. Integrating nanotechnology and artificial intelligence leads to more innovative technologies. Artificial intelligence quickly mines data and makes decisions more quickly and accurately. Machine learning as a subset of the broader artificial intelligence has been used in nanomedicine to design safer nanomaterials. Here, how challenges of developing cell-based drug delivery systems can be solved with potential predictive models of artificial intelligence and machine learning is portrayed. The most famous cell-based drug delivery systems and their challenges are described. Last but not least, artificial intelligence and most of its types used in nanomedicine are highlighted. The present Review has shown the challenges of developing cells or their derivatives as carriers and how they can be used with potential predictive models of artificial intelligence and machine learning.


Asunto(s)
Inteligencia Artificial , Aprendizaje Automático , Nanotecnología , Nanomedicina , Sistemas de Liberación de Medicamentos
4.
Mol Pharm ; 20(3): 1531-1548, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36763486

RESUMEN

The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by "a lipophilic gate" as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug's blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.


Asunto(s)
Péptidos de Penetración Celular , Glioblastoma , Nanopartículas , Humanos , Metotrexato , Dióxido de Silicio/química , Portadores de Fármacos/química , Nanopartículas/química , Encéfalo , Sistemas de Liberación de Medicamentos/métodos , Porosidad
5.
Mol Biol Rep ; 50(5): 4675-4686, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37022526

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that involves young individuals. The drug delivery systems now are available for this disease have chronic and non-targeted effects on the patients. Because of the presence of BBB (blood-brain-barrier), their concentration in the CNS (central nervous system) is low. Because of this flaw, it is critical to use innovative active targeted drug delivery methods. RESULT: Platelets are blood cells that circulate freely and play an important role in blood hemostasis. In this review, we emphasize the various roles of activated platelets in the inflammatory condition to recruit other cells to the injured area and limit inflammation. Besides, the activated platelets in the different stages of the MS disease play a significant role in limiting the progression of inflammation in the peripheral area and CNS. DISCUSSION: This evidence indicates that a platelet-based drug delivery system can be an efficient biomimetic candidate for drug targeting to the CNS and limiting the inflammation in the peripheral and central areas for MS therapy.


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Sistema Nervioso Central , Plaquetas , Barrera Hematoencefálica , Inflamación
6.
Nanomedicine ; 44: 102575, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35714923

RESUMEN

A cell-based drug delivery system based on yeast-cell wall loaded with sitagliptin, a drug with an anti-inflammatory effect, was developed to control neuroinflammation associated with Alzheimer's disease. The optimized nanoparticles had a spherical shape with a negative surface charge, and were shown to be less toxic than the carrier and sitagliptin. Moreover, the nanoparticles caused anti-inflammatory effects against tumor necrosis factor-alpha in mice model of neuroinflammation. The pharmacokinetics study showed the brain concentration of drug in the nanoparticles group was much higher than in the control group. To evaluate the effect of P-glycoprotein on brain entry of sitagliptin, the experiment was repeated with verapamil, as a P-glycoprotein inhibitor. Brain concentration of the nanoparticles group remained approximately unchanged, proving the "Trojan Horse" effect of the developed nanocarriers. The results are promising for using yeast-cell wall as a carrier for targeted delivery to immune cells for the management of inflammation.


Asunto(s)
Enfermedad de Alzheimer , Subfamilia B de Transportador de Casetes de Unión a ATP/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Pared Celular/metabolismo , Ratones , Enfermedades Neuroinflamatorias , Saccharomyces cerevisiae , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/uso terapéutico
7.
Phytother Res ; 36(4): 1785-1796, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35266219

RESUMEN

This study aimed to investigate the health-related effects of microencapsulated fermented garlic extract (FGE) containing dark chocolate in hypertensive adults. For this purpose, 36 hypertensive adults (15 males vs. 21 females) were randomized to receive the FGE (5 g/day) dark chocolate containing 650 mg of FGE powder or the placebo. Intervention periods lasted for 6 weeks and were separated by a 3-week wash-out period. The response variables included blood pressure, anthropometric indices, lipid profile, and inflammatory and oxidative stress indices. Statistical analyses were performed using the Pkcross procedure, and Cohen's d was estimated for all response variables. There was no significant inter-period difference between the mean changes of body weight, waist circumference, and body mass index (BMI). Furthermore, no significant change was confirmed in participants' blood pressure, triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), serum homocysteine, high-sensitive c-reactive protein (hs-CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC). It seems that the dose of FGE used in this study was not sufficient to cause any significant changes in the outcomes. Therefore, further studies with dose-response designs and longer durations are recommended.


Asunto(s)
Chocolate , Ajo , Hipertensión , Adulto , Antioxidantes/farmacología , Método Doble Ciego , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Lipoproteínas LDL , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
8.
J Theor Biol ; 483: 109992, 2019 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-31493485

RESUMEN

Signal integration has a crucial role in the cell fate decision and dysregulation of the cellular signaling pathways is a primary characteristic of cancer. As a signal integrator, mTOR shows a complex dynamical behavior which determines the cell fate at different cellular processes levels, including cell cycle progression, cell survival, cell death, metabolic reprogramming, and aging. The dynamics of the complex responses to rapamycin in cancer cells have been attributed to its differential time-dependent inhibitory effects on mTORC1 and mTORC2, the two main complexes of mTOR. Two explanations were previously provided for this phenomenon: 1-Rapamycin does not inhibit mTORC2 directly, whereas it prevents mTORC2 formation by sequestering free mTOR protein (Le Chatelier's principle). 2-Components like Phosphatidic Acid (PA) further stabilize mTORC2 compared with mTORC1. To understand the mechanism by which rapamycin differentially inhibits the mTOR complexes in the cancer cells, we present a mathematical model of rapamycin mode of action based on the first explanation, i.e., Le Chatelier's principle. Translating the interactions among components of mTORC1 and mTORC2 into a mathematical model revealed the dynamics of rapamycin action in different doses and time-intervals of rapamycin treatment. This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Based on our results, even when mTORC2 is less stable compared with mTORC1, it can be less inhibited by rapamycin.


Asunto(s)
Modelos Biológicos , Neoplasias/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Humanos , Cinética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Sirolimus/farmacología , Factores de Tiempo
9.
Pharm Dev Technol ; 24(7): 812-823, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30889371

RESUMEN

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600 nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60-85% of drug was slowly released from lipid nanoparticles within 72 h. CPA-NLC with average diameter of 600 nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300 nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300 nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300 nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Acetato de Ciproterona/administración & dosificación , Portadores de Fármacos/química , Lípidos/química , Absorción Cutánea , Antagonistas de Andrógenos/farmacocinética , Animales , Cricetinae , Acetato de Ciproterona/farmacocinética , Folículo Piloso/metabolismo , Masculino , Nanopartículas/química , Tamaño de la Partícula
10.
J Pharm Pharm Sci ; 21(1): 305-317, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30053381

RESUMEN

PURPOSE: Although it passes through blood-brain barrier (BBB) very poorly, methotrexate (MTX) is an important therapeutic in the treatment of many central nervous system malignancies. Accordingly, intranasal (IN) administration accompanied with a muco-adhesive chitosan-based nanoformulation is expected to overcome this problem. METHODS: Nanogel containing MTX was prepared through an ionic gelation method and then characterized in terms of particle size, morphology, zeta potential, drug loading and drug release behavior. The drug release results were fitted on eight mathematical models to choose the model best describing the phenomenon. Then the nano-formulation and free drug solution in deionized water as control were administered in the nasal cavity for rats and after 15, 30, 60 and 240 minutes their brain and plasma were analyzed for MTX quantity. RESULTS: The nano-formulation demonstrated an average particle size near 100 nm with a zeta potential of 18.65±1.77 mv. Loading efficiency and loading capacity were calculated to be 65.46±7.66 and 3.02±0.34 respectively. The Weibull model was found to be best describing the release phenomenon as a combination of swelling and Fickian diffusion. Moreover in in vivo studies, drug targeting efficiency and direct transport percentage for nanogel (test) and free drug solution (control) were 424.88% and 76.46% and 34842.15% and 99.71% respectively.  Conclusion: According to in vivo studies, nanogel produced significantly higher concentration of MTX in the brain but not in the plasma when compared to the free drug solution. Besides, in comparison to intravenous administration of the same nanogel it was indicated that intranasal administration significantly increases the brain concentration of MTX.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Hidrogeles/farmacocinética , Linfoma/tratamiento farmacológico , Metotrexato/farmacocinética , Nanopartículas/química , Administración Intranasal , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Encéfalo/metabolismo , Liberación de Fármacos , Hidrogeles/administración & dosificación , Hidrogeles/uso terapéutico , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie , Distribución Tisular
11.
Neurol Sci ; 39(8): 1345-1353, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29808331

RESUMEN

Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48 ± 0.01 µl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p < 0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.


Asunto(s)
Azulenos/administración & dosificación , Manzanilla/química , Migraña sin Aura/tratamiento farmacológico , Administración Tópica , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Flores/química , Humanos , Masculino , Persona de Mediana Edad , Migraña sin Aura/complicaciones , Náusea/tratamiento farmacológico , Náusea/etiología , Compuestos Orgánicos/administración & dosificación , Dimensión del Dolor , Fitoterapia/métodos , Factores de Tiempo , Resultado del Tratamiento , Escala Visual Analógica
12.
Iran J Med Sci ; 41(3 Suppl): S6, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27840472

RESUMEN

BACKGROUND: As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. METHODS: By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. RESULTS: The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC50 >100 µg/ml) was calculated for the methanol extract of tablets. CONCLUSION: Carrying out and validating a GC method for standardization of the formulated tablet, and having the structure for the effectiveness of these medicinal herbs in Alzheimer may be the horizon for a new Alzheimer-targeted medicine.

13.
Phys Rev Lett ; 112(22): 225502, 2014 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-24949777

RESUMEN

We study the structural features and underlying principles of multidislocation ground states of a crystalline spherical cap. In the continuum limit where the ratio of crystal size to lattice spacing W/a diverges, dislocations proliferate and ground states approach a characteristic sequence of structures composed of radial grain boundaries ("neutral scars"), extending radially from the boundary and terminating in the bulk. Employing a combination of numerical simulations and asymptotic analysis of continuum elasticity theory, we prove that an energetic hierarchy gives rise to a structural hierarchy, whereby dislocation number and scar number diverge as a/W→0 while scar length and dislocation number per scar become independent of lattice spacing. We characterize a secondary transition occurring as scar length grows, where the n-fold scar symmetry is broken and ground states are characterized by polydisperse, forked-scar morphologies.

14.
Heliyon ; 10(2): e24217, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38293392

RESUMEN

The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with sodium fluoride (NaF) and nanohydroxyapatite (nHA) to treat demineralization. The chemical structure and morphology of the formulation were characterized using FTIR and FESEM-EDS tests. Hydrogel texture, rheology, and stability were also examined. The hydrogel was in a sol state at room temperature and became gel after being placed at 37 °C with no significance different in gelation time with the formulation without nHA and NaF as observed by t-test. The FTIR spectrum of nHA/NaF/chitosan-based hydrogel indicated the formation of physical crosslinking without any chemical interactions between the hydrogel components. The FESEM-EDS results demonstrated the uniform distribution of each element within the hydrogel matrix, confirming the successful incorporation of nHA and NaF in the prepared gel. The hardness, hydrogel's adhesiveness, and cohesiveness were 0.9 mJ, 1.7 mJ, and 0.37, respectively, indicating gel stability and the acceptable retention time of hydrogels. The formulation exhibited a non-Newtonian shear-thinning pseudoplastic and thixotropic behavior with absolute physical stability. Within the limitation of in vitro studies, nHA/NaF/chitosan-based in situ forming gel demonstrated favorable properties, which could be trasnsorm into a gel state in oral cavity due to poloxamer and chitosan and can prevent dental caries due to nHA and NaF. We propose this formulation as a promising dental material in tooth surface remineralization.

15.
Biomimetics (Basel) ; 9(4)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38667253

RESUMEN

Due to the high pollution of the transportation sector, nowadays the role of electric vehicles has been noticed more and more by governments, organizations, and environmentally friendly people. On the other hand, the problem of electric vehicle routing (EVRP) has been widely studied in recent years. This paper deals with an extended version of EVRP, in which electric vehicles (EVs) deliver goods to customers. The limited battery capacity of EVs causes their operational domains to be less than those of gasoline vehicles. For this purpose, several charging stations are considered in this study for EVs. In addition, depending on the operational domain, a full charge may not be needed, which reduces the operation time. Therefore, partial recharging is also taken into account in the present research. This problem is formulated as a multi-objective integer linear programming model, whose objective functions include economic, environmental, and social aspects. Then, the preemptive fuzzy goal programming method (PFGP) is exploited as an exact method to solve small-sized problems. Also, two hybrid meta-heuristic algorithms inspired by nature, including MOSA, MOGWO, MOPSO, and NSGAII_TLBO, are utilized to solve large-sized problems. The results obtained from solving the numerous test problems demonstrate that the hybrid meta-heuristic algorithm can provide efficient solutions in terms of quality and non-dominated solutions in all test problems. In addition, the performance of the algorithms was compared in terms of four indexes: time, MID, MOCV, and HV. Moreover, statistical analysis is performed to investigate whether there is a significant difference between the performance of the algorithms. The results indicate that the MOSA algorithm performs better in terms of the time index. On the other hand, the NSGA-II-TLBO algorithm outperforms in terms of the MID, MOCV, and HV indexes.

16.
Int J Pharm ; 664: 124590, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39153645

RESUMEN

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.


Asunto(s)
Quemaduras , Quitosano , Geles , Agujas , Cicatrización de Heridas , Quemaduras/tratamiento farmacológico , Quitosano/química , Quitosano/administración & dosificación , Animales , Cicatrización de Heridas/efectos de los fármacos , Humanos , Ratones , Liberación de Fármacos , Hidrocortisona/administración & dosificación , Hidrocortisona/farmacocinética , Hidrocortisona/química , Administración Cutánea , Sistemas de Liberación de Medicamentos , Masculino , Femenino
17.
ACS Biomater Sci Eng ; 10(3): 1207-1234, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38416058

RESUMEN

Biomaterials possess distinctive properties, notably their ability to encapsulate active biological products while providing biocompatible support. The immune system plays a vital role in preventing cancer recurrence, and there is considerable demand for an effective strategy to prevent cancer recurrence, necessitating effective strategies to address this concern. This review elucidates crucial cellular signaling pathways in cancer recurrence. Furthermore, it underscores the potential of biomaterial-based tools in averting or inhibiting cancer recurrence by modulating the immune system. Diverse biomaterials, including hydrogels, particles, films, microneedles, etc., exhibit promising capabilities in mitigating cancer recurrence. These materials are compelling candidates for cancer immunotherapy, offering in situ immunostimulatory activity through transdermal, implantable, and injectable devices. They function by reshaping the tumor microenvironment and impeding tumor growth by reducing immunosuppression. Biomaterials facilitate alterations in biodistribution, release kinetics, and colocalization of immunostimulatory agents, enhancing the safety and efficacy of therapy. Additionally, how the method addresses the limitations of other therapeutic approaches is discussed.


Asunto(s)
Materiales Biocompatibles , Neoplasias , Humanos , Materiales Biocompatibles/uso terapéutico , Distribución Tisular , Sistemas de Liberación de Medicamentos , Inmunoterapia , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
18.
Nutr Diabetes ; 14(1): 66, 2024 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164243

RESUMEN

BACKGROUND: The probiotic potential of Lacticacid bacteria has been studied in various medical complications, from gastrointestinal diseases to antibiotic resistance infections recently. Moreover, diabetic ulcer (DU) is known as one of the most significant global healthcare concerns, which comprehensively impacts the quality of life for these patients. Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial. METHODS: We designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (L. casei), Lactobacillus fermentum (L. fermentum), and Lactobacillus acidophilus (L. acidophilus) individually to investigate their effect on wound healing process as an in vivo study. The wound repair process was closely monitored regarding morphology, biochemical, and histopathological changes over two weeks and compared it with the effects of topical tetracycline as an antibiotic approach. Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens. RESULTS: The findings indicated that all tested lactobacillus groups (excluded L. casei) included in the oleogel-based formulation revealed a high potential for repairing damaged skin due to the considerably more levels of hydroxyproline content of tissue samples along with the higher numerical density of mature fibroblasts cell and volume density of hair follicles, collagen fibrils, and neovascularization in comparison with antibiotic and control groups. L. acidophilus and L. rhamnosus showed the best potential of wound healing among all lactobacillus species, groups treated by tetracycline and control groups. Besides, L. rhamnosus showed a significant biofilm inhibition activity against tested pathogens. CONCLUSIONS: This experiment demonstrated that the designed formulations containing probiotics, particularly L. acidophilus and L. rhamnosus, play a central role in manipulating diabetic wound healing. It could be suggested as an encouraging nominee for diabetic wound-healing alternative approaches, though further studies in detailed clinical trials are needed.


Asunto(s)
Lacticaseibacillus rhamnosus , Lactobacillus acidophilus , Probióticos , Cicatrización de Heridas , Probióticos/administración & dosificación , Probióticos/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Masculino , Lacticaseibacillus casei , Biopelículas/efectos de los fármacos , Lactobacillus , Administración Tópica , Tetraciclina/administración & dosificación , Limosilactobacillus fermentum , Pie Diabético/terapia , Hidroxiprolina/metabolismo , Ratas , Compuestos Orgánicos
19.
Int J Biol Macromol ; 278(Pt 4): 134781, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151860

RESUMEN

Local administration of drugs at tumor sites over an extended period of time shows potential as a promising approach for cancer treatment. In the present study, the temperature-induced phase transition of chitosan and poloxamer 407 is used to construct an injectable hydrogel encapsulating 5-FU-loaded nanoerythrosome (5-FU-NER-gel). The 5-FU-NERs were found to be spherical, measuring approximately 115 ± 20 nm in diameter and having a surface potential of -7.06 ± 0.4. The drug loading efficiency was approximately 40 %. In situ gel formation took place within 15 s when the gel was exposed to body temperature or subcutaneous injection. A sustained release profile was observed at pH 7.4 and 6.8, with a total 5-FU release of 76.57 ± 4.4 and 98.07 ± 6.31 in 24 h, respectively. MTT, Live/dead, and migration assays confirmed the cytocompatibility of the drug carrier and its effectiveness as a chemotherapeutic formulation. After in vivo antitumor assessment in a subcutaneous autograft model, it was demonstrated that tumor growth inhibition in 14 days was 90 %. Therefore, the obtained injectable chitosan-based hydrogel containing 5-FU-loaded nanoerythrosomes illustrated promising potential as a candidate for local and enhanced delivery of chemotherapeutics at the tumor site.


Asunto(s)
Quitosano , Portadores de Fármacos , Fibrosarcoma , Fluorouracilo , Quitosano/química , Fluorouracilo/química , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacología , Animales , Portadores de Fármacos/química , Ratones , Línea Celular Tumoral , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/patología , Hidrogeles/química , Temperatura , Liberación de Fármacos , Nanopartículas/química , Humanos , Poloxámero/química
20.
Sci Rep ; 14(1): 21100, 2024 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256460

RESUMEN

This study aimed to evaluate chitosan (CS)-based formulations loaded with 5% sodium fluoride (NaF) and/or 10% nanohydroxyapatite (nHA) to remineralize the demineralized primary tooth enamel surface. Ninety enamel blocks were demineralized and were divided into six groups (n = 15): (1) CS-based hydrogel, (2) CS-based hydrogel loaded with NaF, (3) CS-based hydrogel loaded with nHA, (4) CS-based hydrogel loaded with NaF and nHA, (5) 5% NaF varnish, and (6) negative control with no intervention. After intervention, the specimens were pH cycled by 2 h immersion in demineralizing solution and 22 h immersion in remineralizing solution for 8 days. The remineralization effects were evaluated by Vickers microhardness measurements and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (FESEM-EDS). The best mean ± SD percentage microhardness recovery in remineralized enamel (%REMH) was found in group 4 (56.90 ± 5.49). The %REMH of groups 2 (30.74 ± 3.51) and 5 (29.23 ± 5.65) were statistically the same (p = 0.943). FESEM images confirmed partial coverage of the porous demineralized enamel with a newly formed mineralized layer. Based on EDS findings, the Ca/P ratio values of the treated enamel surfaces with CS-based hydrogels ranged between 1.71 and 1.87, and the highest F content was noticed in group 2 (1.02 ± 0.03). Although, all tested CS-based hydrogels demonstrated the potential to repair demineralized enamel, nHA- and NaF-containing CS-based hydrogel showed the highest remineralization effect. We infer that this new hybrid hydrogel is a potentially useful dental material for tooth biomineralization.


Asunto(s)
Quitosano , Esmalte Dental , Fluoruro de Sodio , Quitosano/química , Quitosano/farmacología , Fluoruro de Sodio/farmacología , Esmalte Dental/efectos de los fármacos , Esmalte Dental/química , Concentración de Iones de Hidrógeno , Humanos , Remineralización Dental/métodos , Fluoruros Tópicos/farmacología , Fluoruros Tópicos/administración & dosificación , Durapatita/química , Durapatita/farmacología , Hidrogeles/química , Biomineralización/efectos de los fármacos , Desmineralización Dental/prevención & control , Microscopía Electrónica de Rastreo , Geles/química
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