RESUMEN
UV radiation causes long- and short-term skin damage, such as erythema and skin cancer. Therefore, the use of sunscreens is extremely important. However, concerns about UV filter safety have prompted exploration into alternative solutions, with nanotechnology emerging as a promising avenue. This systematic review identified 23 experimental studies utilizing nanocarriers to encapsulate sunscreens with the aim of enhancing their efficacy and safety. Polymeric and lipid nanoparticles are frequently employed to encapsulate both organic and inorganic UV filters along with natural antioxidants. Nanocarriers have demonstrated benefits including reduced active ingredient usage, increased sun protection factor, and mitigated photoinstability. Notably, they also decreased the skin absorption of UV filters. In summary, nanocarriers represent a viable strategy for improving sunscreen formulations, offering enhanced physicochemical properties and bolstered photoprotective effects, thereby addressing concerns regarding UV filter safety and efficacy in cosmetic applications.
Asunto(s)
Nanopartículas , Nanotecnología , Protectores Solares , Rayos Ultravioleta , Protectores Solares/química , Protectores Solares/administración & dosificación , Humanos , Nanopartículas/química , Rayos Ultravioleta/efectos adversos , Nanotecnología/métodos , Portadores de Fármacos/química , Animales , Absorción Cutánea/efectos de los fármacos , Polímeros/química , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Piel/metabolismo , Piel/efectos de los fármacos , Factor de Protección Solar/métodos , Lípidos/químicaRESUMEN
Percutaneous delivery is explored as alternative pathway for addressing the drawbacks associated with the oral administration of otherwise efficacious drugs. Short of breaching the skin by physical means, the preference goes to formulation strategies that augment passive diffusion across the skin. One such strategy lies in the use of skin penetration and permeation enhancers notably of hydroxylated solvents like propylene glycol (PG), ethanol (EtOH), and diethylene glycol monoethyl ether (Transcutol®, TRC). In a previous publication, we focused on the role of Transcutol® as enhancer in neat or diluted systems. Herein, we explore its' role in complex formulation systems, including patches, emulsions, vesicles, solid lipid nanoparticles, and micro or nanoemulsions. This review discusses enhancement mechanisms associated with hydroalcoholic solvents in general and TRC in particular, as manifested in multi-component formulation settings alongside other solvents and enhancers. The principles that govern skin penetration and permeation, notably the importance of drug diffusion due to solubilization and thermodynamic activity in the vehicle (formulation), drug solubilization and partitioning in the stratum corneum (SC), and/or solvent drag across the skin into deeper tissue for systemic absorption are discussed. Emphasized also are the interplay between the drug properties, the skin barrier function and the formulation parameters that are key to successful (trans)dermal delivery.
Asunto(s)
Administración Cutánea , Glicoles de Etileno , Permeabilidad , Absorción Cutánea , Piel , Solventes , Absorción Cutánea/fisiología , Absorción Cutánea/efectos de los fármacos , Glicoles de Etileno/química , Humanos , Piel/metabolismo , Animales , Solventes/química , Química Farmacéutica/métodos , Solubilidad , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Nanopartículas/química , Etanol/química , Etanol/administración & dosificaciónRESUMEN
Recent research has emphasized the development of efficient drug delivery systems to facilitate the delivery of biological compounds such as polyphenols via skin absorption. Phytozomes have been employed as carriers of plant compounds in this context Hydrogen bonding between plant polyphenols and the phospholipid phosphate group enables efficient encapsulation of potent compounds for enhanced drug delivery systems. Additionally, the strong affinity of phytosomes for the skin's phospholipids enhances skin absorption. In this study, phytosomes were initially formulated using the thin-layer hydration method After optimizing the synthetic parameters, phytosomes were loaded with Resveratrol and Quercetin for enhanced delivery and skin absorption potential to assess the characteristics of the synthesized phytosomes, tests were conducted to determine particle distribution and size, zeta potential, and examine the microstructure morphology using a scanning electron microscope (SEM). Furthermore, a siloxane gel base was formulated in this study, and the stability of the physicochemical and biological properties of the final prepared nanoformulation was investigated. The results of this study indicated that the formulated phytosomes exhibit optimal characteristics for facilitating high skin penetration of resveratrol and quercetin. A high skin absorption was observed after 60 days of synthesis. Additionally, the base of the siloxane gel can play a significant role in preventing the formation of scars by reducing the passage of water vapor.
Asunto(s)
Cicatriz , Geles , Quercetina , Resveratrol , Siloxanos , Resveratrol/química , Resveratrol/administración & dosificación , Resveratrol/farmacocinética , Geles/química , Siloxanos/química , Quercetina/química , Quercetina/administración & dosificación , Quercetina/farmacocinética , Absorción Cutánea/efectos de los fármacos , Tamaño de la Partícula , Animales , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Fitoquímicos/química , FitosomasRESUMEN
Luteolin (LN), is an herbal bioactive flavone and exhibits many pharmacological activities. However, the bioavailability of LN is limited due to its inadequate solubility and significant first-pass metabolism. The present study developed transdermal LN-loaded invasomes (IVM) gel to improve the therapeutic efficacy. The LN-IVM was prepared and optimized by 2 3 factorial designs. LN-IVM was characterized for physicochemical parameters. The optimized LN-IVM (LN-IVMopt) was incorporated into HPMC-K4M gel and evaluated for viscosity, spreadability, and irritation. Further LN-IVM gel was evaluated for drug release, ex-vivo permeation, pharmacokinetic and pharmacodynamics study. LN-IVMopt showed 300.8±2.67 nm of VS, 0.258 of PDI, 89.92±1.29% of EE, and a zeta potential of -18.2 mV. LN-IVM exhibited spherical morphology. FTIR and XRD results demonstrated that LN was encapsulated into IVM matrix. The optimized IVM gel (LN-IVMoptG2) exhibited excellent viscosity, spreadability, and sustained release of LN (91.32±2.95% in 24 h). LN-IVMoptG2 exhibited statistically significant (p < 0.05) higher flux (5.79 µg/h/cm2 ) than LN-gel (2.09 µg/h/cm2 ). The apparent permeability coefficient of plain LN gel and LN- IVMoptG was 1.15×10-5 cm/min and 3.22×10-5 cm/min respectively. LN-IVMoptG2 showed no irritation (score 0.0) throughout the study (60 min). The relative bioavailability of LN from LN-IVMopt-G2 (transdermal) was 2.38±0.19 fold as compared to LN-Sus (oral) and 1.81±0.15-fold than plain LN-gel (transdermal). The LN-IVMoptG2 showed a substantial lessening in the paw volume up to 12 h (17.48±1.94% swelling) than plain LN-gel (44.77±2.82% swelling). The finding concluded that the IVM gel is a novel, effective, and safe approach for the delivery of LN transdermally to improve its therapeutic efficacy.
Asunto(s)
Administración Cutánea , Liberación de Fármacos , Geles , Luteolina , Animales , Luteolina/administración & dosificación , Luteolina/farmacocinética , Viscosidad , Absorción Cutánea/efectos de los fármacos , Solubilidad , Masculino , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Fenómenos Químicos , Permeabilidad , Ratas Sprague-DawleyRESUMEN
In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.
Asunto(s)
Administración Cutánea , Ácido Oléico , Absorción Cutánea , Tiroxina , Ácido Oléico/química , Tiroxina/administración & dosificación , Tiroxina/farmacología , Tiroxina/farmacocinética , Animales , Absorción Cutánea/efectos de los fármacos , Parche Transdérmico , Piel/metabolismo , Piel/efectos de los fármacos , Liberación de Fármacos , Ratones , Permeabilidad , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/metabolismo , Humanos , Química Farmacéutica/métodos , MasculinoRESUMEN
Transdermal administration techniques have gained popularity due to their advantages over oral and parenteral methods. Noninvasive, self-administered delivery devices improve patient compliance and control drug release. Transdermal delivery devices struggle with the skin's barrier function. Molecules over 500 Dalton (Da) and ionized compounds don't permeate through the skin. Drug encapsulation in phospholipid-based vesicular systems is the most effective skin delivery technique. Vesicular carriers include bi-layered liposomes, ultra-deformable liposomes, ethanolic liposomes, transethosomes, and invasomes. These technologies enhance skin drug permeation by increasing formula solubilization, partitioning into the skin, and fluidizing the lipid barrier. Phospholipid-based delivery systems are safe and efficient, making them a promising pharmaceutical and cosmeceutical drug delivery technique. Still, making delivery systems requires knowledge about the physicochemical properties of the drug and carrier, manufacturing and process variables, skin delivery mechanisms, technological advances, constraints, and regulatory requirements. Consequently, this review covers recent research achievements addressing the mentioned concerns.
Asunto(s)
Administración Cutánea , Sistemas de Liberación de Medicamentos , Liposomas , Fosfolípidos , Absorción Cutánea , Piel , Fosfolípidos/química , Humanos , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Absorción Cutánea/fisiología , Absorción Cutánea/efectos de los fármacos , Liposomas/química , Portadores de Fármacos/química , Animales , Nanopartículas/químicaRESUMEN
Winlevi® (clascoterone) topical cream (1%, w/w) was approved by the U.S. FDA for the treatment of acne vulgaris in patients 12 years of age and older. The active ingredient, clascoterone, is not stable in physiological solutions and can hydrolyze to cortexolone at body temperature. Instability of clascoterone poses a significant challenge in accurately assessing the rate and extent of clascoterone permeation in vitro. Therefore, the purpose of this study was to develop an in vitro skin permeation test (IVPT) method, and a robust analytical method, that can minimize hydrolyzation of clascoterone during the study for quantification of clascoterone. Two IVPT methods, using either vertical diffusion cells or flow-through cells, were developed and compared to evaluate in vitro permeation of clascoterone from Winlevi. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed to monitor the level of clascoterone and cortexolone in the IVPT samples. The analytical method features a 2-min high-throughput analysis with good linearity, selectivity, and showed a lower limit of quantitation (LLOQ) of 0.5 ng/mL for both clascoterone and cortexolone. The in vitro skin permeation of clascoterone and cortexolone was observed as early as 2 h in both IVPT methods. A substantive amount of clascoterone was found to hydrolyze to cortexolone when using the vertical static diffusion cells with aliquot sampling. Conversely, degradation of clascoterone was significantly minimized when using the flow-through diffusion cells with fractional sampling. The data enhanced our understanding of in vitro permeation of clascoterone following topical application of the Winlevi topical cream, 1% and underscores the importance of IVPT method development and optimization during product development.
Asunto(s)
Cortodoxona , Absorción Cutánea , Crema para la Piel , Espectrometría de Masas en Tándem , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología , Crema para la Piel/farmacocinética , Crema para la Piel/administración & dosificación , Cortodoxona/administración & dosificación , Cortodoxona/farmacocinética , Cortodoxona/metabolismo , Cortodoxona/análogos & derivados , Espectrometría de Masas en Tándem/métodos , Piel/metabolismo , Administración Cutánea , Cromatografía Liquida/métodos , Animales , Permeabilidad , Porcinos , Humanos , PropionatosRESUMEN
Trazodone is a triazolpyridine derivative approved for the treatment of depression, and currently marketed as oral formulations. The transdermal administration of this drug could reduce side effects, related to peak plasma concentration, and improve patient adherence due to a reduced administration frequency. The aims of this work were: (a) the evaluation of the effect of pH vehicle and permeation enhancers on trazodone permeability across porcine skin ex-vivo; (b) the development and optimization of a transdermal drug delivery system containing trazodone hydrochloride. From the results obtained, it was found that the effect of pH of the vehicle on the permeation of trazodone across the skin is quite complex, because it influences both solubility and partitioning and that the presence of fatty acids in the vehicle has a notable effect on permeation (the enhancement factor obtained was approx. 100). For both the fatty acid selected (oleic and lauric) a parabolic relationship between the transdermal flux and the concentration was found, with an optimum activity in the range 2-3 %. In the second part of the work, different patches were prepared and tested ex-vivo. Overall, the results obtained seem to highlight that drug loading, rather than the components of the adhesive matrix, plays the most relevant role for the permeation of trazodone. The addition of lauric acid, which produced a considerable enhancement in solution, was not effective when included in the patch. The obtained data are promising although probably not clinically relevant for the treatment of depression, but might be interesting for the treatment of insomnia and anxiety disorder, which require much lower doses.
Asunto(s)
Administración Cutánea , Absorción Cutánea , Trazodona , Trazodona/administración & dosificación , Trazodona/farmacocinética , Animales , Porcinos , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Permeabilidad , Ácido Oléico/química , Solubilidad , Concentración de Iones de Hidrógeno , Ácidos Láuricos/química , Ácidos Láuricos/administración & dosificación , Parche Transdérmico , Química Farmacéutica/métodos , Antidepresivos de Segunda Generación/administración & dosificación , Antidepresivos de Segunda Generación/farmacocinética , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.
Asunto(s)
Administración Cutánea , Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Donepezilo , Sistemas de Liberación de Medicamentos , Agujas , Impresión Tridimensional , Donepezilo/administración & dosificación , Donepezilo/química , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Células 3T3 NIH , Sistemas de Liberación de Medicamentos/métodos , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/farmacocinética , Inhibidores de la Colinesterasa/química , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Liberación de Fármacos , Parche Transdérmico , HumanosRESUMEN
Terpene-based eutectic mixtures (EMs) are attractive platforms for transdermal delivery due to their solubilizing potential and ability to alter the barrier function of the stratum corneum (SC). Despite this, little is known about the effect of diluting EMs with co-solvents (CSs) on their solubility- and permeation-enhancing properties. Furthermore, insufficient attention has been paid to comparing these platforms with traditional solvents, such as propylene glycol (PG) or ethanol (EtOH). To address this gap, the present study investigates the impact of the CS content in EM:CS blends on the transdermal delivery of clotrimazole (CLOT). Two CSs, PG and EtOH, and two terpene-based EMs, menthol:thymol and thymol:ß-citronellol, were used. Each of the EMs was investigated at two different molar ratios between the terpenes, with one being their eutectic point, to explore its potential benefit for skin permeation. At each step, properties of the blends were compared with those of pure CSs. The EM:CS blends showed a better solubilizing potential for CLOT than EMs or CSs on their own. A higher content of CSs in the blends resulted in a higher skin permeation and retention of CLOT, and a lower degree of disarrangement of the SC structure. Furthermore, the blends of EMs at their EPs led to overall poorer permeation profiles, implying that the permeation rate is more affected by the properties of the individual terpenes than by the specific ratio at the eutectic point between them. In conclusion, addition of CSs to the EMs promotes permeation and retention of CLOT, while reducing the skin impairment caused by the terpenes.
Asunto(s)
Administración Cutánea , Etanol , Mentol , Propilenglicol , Absorción Cutánea , Piel , Solubilidad , Solventes , Terpenos , Absorción Cutánea/efectos de los fármacos , Animales , Solventes/química , Terpenos/química , Terpenos/administración & dosificación , Piel/metabolismo , Etanol/química , Etanol/administración & dosificación , Mentol/química , Mentol/administración & dosificación , Propilenglicol/química , Clotrimazol/administración & dosificación , Clotrimazol/química , Clotrimazol/farmacocinética , Permeabilidad , Timol/química , Timol/administración & dosificación , Porcinos , Sistemas de Liberación de MedicamentosRESUMEN
Synthetic single-chain bolalipids (SSCBs) are novel excipients in drug delivery, with potential as stabilizers or solubilizers. However, their impact on skin barrier function has not been comprehensively studied. Therefore, two SSCBs (PC-C24-PC and PC-C32-PC) were studied in aqueous systems for their impact on penetration of a model permeant into porcine skin. Concentrations of 0.05 - 5 % w/w were tested; PC-C24-PC formulations were low-viscosity liquids while PC-C32-PC formed viscous dispersions to gels at room temperature. Formulations were compared for their ability to enhance sodium fluorescein penetration (SF, 0.1 % w/w) into skin via tape stripping. Using NIR-densitometry, the effect of SSCB formulations on corneocyte cohesion was evaluated. Data were compared with phospholipid mixture Lipoid S-75, sodium dodecyl sulfate (SDS), and polyethylene glycol 12-hydroxystearate (PEG-HS), and distilled water as negative control. Contrary to the hypothesis, both SSCBs failed to increase SF penetration into the stratum corneum, but rather showed a significant decrease in penetration depth compared to water. Both SSCBs exhibited a keratolytic effect at 5 % w/w, leading to substantial removal of proteins from the skin surface. Consequently, SSCBs may not enhance penetration of hydrophilic drugs into skin, but could be used as keratolytic agents.
Asunto(s)
Excipientes , Interacciones Hidrofóbicas e Hidrofílicas , Absorción Cutánea , Piel , Porcinos , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Excipientes/química , Sistemas de Liberación de Medicamentos/métodos , Administración Cutánea , Fluoresceína , Viscosidad , Química Farmacéutica/métodos , PermeabilidadRESUMEN
Transdermal drug delivery (TDD) has attracted widespread attention because of the advantage of its non-invasive nature, easy self-administration, and low side effects. The key to this pathway of drug delivery is how to overcome the barrier of the lipid matrix in the stratum corneum (SC). In this work, molecular dynamics (MD) were employed to investigate the adsorption of thyrotropin-releasing hormone (TRH) on the SC, and the effects of three different chemical permeation enhancers (ethanol (ETOH), carveol (CAV), and borneol (BOR)) on the SC were analyzed. The results showed that ETOH hardly altered the order of lipids in the SC, while CAV and BOR disrupted the morphology of the SC. The primary target of CAV was the CHOL in SC, which not only disrupted the ordered arrangement of CHOL, but also "extracted" CHOL from SC. The thickness distribution of SC became more inhomogeneous in the presence of CAV and BOR, which facilitated the penetration of drug molecules. Compared to no chemical permeation enhancers, the free energy of permeation in the presence of chemical permeation enhancers was less than 4-10â¯kcalâ¯mol-1, which suggested that chemical permeation enhancers were more favorable for the permeation of drugs from viewpoints of thermodynamics. All the results provided theoretical insights into the effect of chemical permeation enhancers on the transdermal permeation of drugs.
Asunto(s)
Administración Cutánea , Sistemas de Liberación de Medicamentos , Absorción Cutánea , Adsorción , Absorción Cutánea/efectos de los fármacos , Simulación de Dinámica Molecular , Permeabilidad , Etanol/química , Canfanos/química , Canfanos/farmacología , Piel/metabolismo , Piel/efectos de los fármacosRESUMEN
The stratum corneum of the skin presents the initial barrier to transdermal penetration. The dense structure of the extracellular matrix (ECM) further impedes local drug dispersion. Hyaluronidase (HAase) is a key component for the degradation of glycosidic bonding sites in hyaluronic acid (HA) within the ECM to overcome this barrier and enhance drug dispersion. HAase activity is optimal at 37-45 °C and in the pH range 4.5-5.5. Numerous FDA-approved formulations are available for the clinical treatment of extravasation and other diseases. HAase combined with various new nanoformulations can markedly improve intradermal dispersion. By degrading HA to create tiny channels that reduce the ECM density, these small nanoformulations then use these channels to deliver drugs to deeper layers of the skin. This deep penetration may increase local drug concentration or facilitate penetration into the blood or lymphatic circulation. Based on the generalization of 114 studies from 2010 to 2024, this article summarizes the most recent strategies to overcome the HAase-based ECM barrier for local drug delivery, discusses opportunities and challenges in clinical applications, and provides references for the future development of HAase. In the future, HAase-assisted topical administration is necessary to achieve systemic effects and to standardize HAase application protocols.
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Administración Cutánea , Sistemas de Liberación de Medicamentos , Matriz Extracelular , Ácido Hialurónico , Hialuronoglucosaminidasa , Hialuronoglucosaminidasa/administración & dosificación , Hialuronoglucosaminidasa/metabolismo , Matriz Extracelular/metabolismo , Humanos , Sistemas de Liberación de Medicamentos/métodos , Ácido Hialurónico/química , Ácido Hialurónico/administración & dosificación , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Nanopartículas/químicaRESUMEN
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
Asunto(s)
Emulsiones , Macrófagos Peritoneales , Sesquiterpenos Monocíclicos , Sesquiterpenos , Piel , Animales , Sesquiterpenos Monocíclicos/farmacología , Sesquiterpenos Monocíclicos/química , Emulsiones/química , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/química , Piel/parasitología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Espectroscopía Infrarroja por Transformada de Fourier , Absorción Cutánea/efectos de los fármacos , Ratones Endogámicos BALB C , Femenino , Leishmania/efectos de los fármacos , Tensoactivos/farmacología , Tensoactivos/química , Antiprotozoarios/farmacología , Antiprotozoarios/químicaRESUMEN
The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of ß-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/ß-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.
Asunto(s)
Alopecia , Emulsiones , Folículo Piloso , Panax notoginseng , Saponinas , Tensoactivos , Alopecia/tratamiento farmacológico , Alopecia/inducido químicamente , Animales , Ratones , Saponinas/administración & dosificación , Saponinas/farmacología , Saponinas/química , Folículo Piloso/efectos de los fármacos , Panax notoginseng/química , Tensoactivos/química , Tensoactivos/administración & dosificación , Femenino , Piel/efectos de los fármacos , Piel/metabolismo , Movimiento Celular/efectos de los fármacos , Masculino , Absorción Cutánea/efectos de los fármacos , Agua/química , Administración CutáneaRESUMEN
RATIONAL: Nickel is one of humans' most prevalent triggers of allergic contact dermatitis. However, the underlying mechanisms of this allergy still need to be fully understood. One aspect that has yet to be explored is the direct impact of common metal allergens on the skin's metabolites and lipids composition. METHOD: Our study employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to analyze spatially resolved metabolic alterations induced by nickel exposure. Cross-sections of ex vivo porcine ear skin exposed to increasing nickel (II) ion concentrations (17-167 µg/cm2) were measured with an AP-SMALDI5 AF ion source coupled to Q Exactive HF Orbitrap mass spectrometer. Additionally, the penetration of nickel ions into the skin was observed through its pink complexation with dimethylglyoxime under light microscopy. RESULTS: For nickel ion concentrations up to 84 µg/cm2, most nickel ions were stopped within the stratum corneum, while only a very small proportion of nickel ions penetrated the viable epidermis and dermis. Stratum corneum locations with high nickel ion concentrations showed a decrease in arginine and ceramides. Furthermore, several phosphatidylcholine and sphingomyelin species were found to be downregulated in the viable epidermis and dermis due to the nickel exposure. CONCLUSION: Nickel penetrates at a trace level into the viable skin and induces severe metabolomic and lipidomic changes in the stratum corneum, epidermis, and dermis, indicating a change in the skin (barrier) function. These findings contribute to a deeper understanding of nickel-induced skin allergies and provide a solid foundation for further research.
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Níquel , Piel , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Animales , Porcinos , Níquel/análisis , Níquel/metabolismo , Níquel/farmacocinética , Piel/metabolismo , Piel/efectos de los fármacos , Piel/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Oído , Absorción Cutánea/efectos de los fármacosRESUMEN
Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.
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Puntos de Acupuntura , Sistemas de Liberación de Medicamentos , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacocinética , Absorción Cutánea/efectos de los fármacos , Meridianos , Medicina Tradicional China , Administración CutáneaRESUMEN
In part I, we reported Hansen solubility parameters (HSP, HSPiP program), experimental solubility at varied temperatures for TOTA delivery. Here, we studied dose volume selection, stability, pH, osmolality, dispersion, clarity, and viscosity of the explored combinations (I-VI). Ex vivo permeation and deposition studies were performed to observe relative diffusion rate from the injected site in rat skin. Confocal laser scanning microscopy (CLSM) study was conducted to support ex vivo findings. Moreover, GastroPlus predicted in vivo parameters in humans and the impact of various critical factors on pharmacokinetic parameters (PK). Immediate release product (IR) contained 60% of PEG400 whereas controlled release formulation (CR) contained PEG400 (60%), water (10%) and d-limonene (30%) to deliver 2 mg of TOTA. GastroPlus predicted the plasma drug concentration of weakly basic TOTA as function of pH (from pH 2.0 to 9). The cumulative drug permeation and drug deposition were found to be in the order as B-VIË C-VIËA-VI across rat skin. This finding was further supported with CLSM. Moreover, IR and CR were predicted to achieve Cmax of 0.0038 µg/ mL and 0.00023 µg/mL, respectively, after sub-Q delivery. Added limonene in CR extended the plasma drug concentration over period of 12 h as predicted in GastroPlus. Parameters sensitivity analysis (PSA) assessment predicted that sub-Q blood flow rate is the only factor affecting PK parameters in IR formulation whereas this was insignificant for CR. Thus, sub-Q delivery CR would be promising alternative with ease of delivery to children and aged patient.
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Absorción Cutánea , Solubilidad , Tartrato de Tolterodina , Animales , Ratas , Humanos , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología , Tartrato de Tolterodina/administración & dosificación , Tartrato de Tolterodina/farmacocinética , Termodinámica , Solventes/química , Piel/metabolismo , Concentración de Iones de Hidrógeno , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/administración & dosificación , Terpenos/química , Terpenos/administración & dosificación , Terpenos/farmacocinética , Administración Cutánea , Limoneno/administración & dosificación , Limoneno/farmacocinética , Limoneno/química , Masculino , Polietilenglicoles/química , Sistemas de Liberación de Medicamentos/métodos , Química Farmacéutica/métodos , Ciclohexenos/química , Ciclohexenos/farmacocinética , Ciclohexenos/administración & dosificación , Ratas Sprague-DawleyRESUMEN
The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in ß-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from ß-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure.
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Administración Cutánea , Alopecia , Cabello , Minoxidil , Minoxidil/administración & dosificación , Minoxidil/farmacocinética , Animales , Alopecia/tratamiento farmacológico , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Absorción Cutánea/efectos de los fármacos , beta-Ciclodextrinas/química , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/administración & dosificación , Masculino , Técnicas Fotoacústicas/métodos , Humanos , GelesRESUMEN
Based on the structure of the Stratum corneum (SC) the potential penetration/diffusion pathways of drugs and cosmetic actives through the SC are presented and discussed. The well-known lipophilic pathway across the SC is presented and relevant examples are used to show that highly lipophilic molecules such as glucocorticoids, coenzyme Q10 etc. are accumulated in the SC and penetrate into the inner liquid like layer of the SC lipid bilayer by lateral diffusion. The diffusion into and across the SC of highly hydrophilic drugs and active substances such as urea, amino acids and peptides is still under discussion. Another diffusion pathway for the highly hydrophilic molecules via the corneocytes and the corneodesmosomes is presented and discussed, the corneocytary diffusion pathway.