RESUMEN
Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.
Asunto(s)
Antibacterianos , Quitosano , Hidrogeles , Paeonia , Extractos Vegetales , Hojas de la Planta , Quitosano/química , Quitosano/farmacología , Quitosano/análogos & derivados , Femenino , Animales , Hidrogeles/química , Hidrogeles/farmacología , Hojas de la Planta/química , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Paeonia/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st-FA/OBSP (CSOB-FA1st) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.
Asunto(s)
Quitosano , Hidrogeles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Quitosano/química , Ratas , Porcinos , Reactivos de Enlaces Cruzados/química , Ratas Sprague-Dawley , Porcinos Enanos , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacología , Polisacáridos/química , Polisacáridos/farmacologíaRESUMEN
Wound healing is a dynamic and complex biological process, and traditional biological excipients cannot meet the needs of the wound healing process, and there is an urgent need for a biological dressing with multifunctionality and the ability to participate in all stages of wound healing. This study developed tea polyphenol (TP) incorporated multifunctional hydrogel based on oxidized Bletilla striata polysaccharide (OBSP) and adipic acid dihydrazide modified gelatin (Gel-ADH) with antimicrobial, antioxidant hemostatic, and anti-inflammatory properties to promote wound healing. The composite OBSP, Gel-ADH, TP (OBGTP) hydrogels prepared by double crosslinking between OBSP, TP and Gel-ADH via Schiff base bonding and hydrogen bonding had good rheological and swelling properties. The introduction of TP provided the composite hydrogel with excellent antioxidant antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil). In the rat liver hemorrhage model and skin injury model, the OBGTP composite hydrogel had significant (p < 0.001) hemostatic ability, and had the ability to accelerate collagen deposition, reduce the expression of inflammatory factors, and promote rapid wound healing. In addition, OBGTP hydrogels had adhesive properties and good biocompatibility. In conclusion, OBGTP multifunctional composite hydrogels have great potential for wound healing applications.
Asunto(s)
Hemostáticos , Orchidaceae , Animales , Ratas , Gelatina , Hidrogeles , Antioxidantes/farmacología , Staphylococcus aureus , Cicatrización de Heridas , Antibacterianos/farmacología , Escherichia coli , Polifenoles/farmacología , TéRESUMEN
Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and ß-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.
Asunto(s)
Quitosano , Colitis Ulcerosa , Nanopartículas , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Quitosano/uso terapéutico , Hidrogeles/uso terapéutico , Ácido Hialurónico/uso terapéutico , Sistemas de Liberación de Medicamentos , Polisacáridos/uso terapéutico , Inflamación/tratamiento farmacológicoRESUMEN
Bletilla striata polysaccharide (BSP) is a naturally occurring polysaccharide that demonstrates notable biocompatibility and biodegradability. Additionally, BSP possesses therapeutic attributes, including anti-inflammatory and reparative actions. Herein, we report a novel BSP hydrogel prepared using 1,4-butanediol diglycidyl ether (BDDE) as a cross-linking agent. The hydrogel was synthesized via condensation of the hydroxyl group in the BSP molecule with the epoxy group in BDDE. This technique of preparation preserves BSP's natural properties while avoiding any potentially hazardous or adverse effects that may occur during the chemical alteration. Compared with BSP before crosslinking, BSP hydrogel has distinct advantages, such as a three-dimensional network structure, improved water retention, enhanced swelling capacity, greater thermal stability, and superior mechanical properties. Experiments on in vitro cytotoxicity, hemolysis, and degradation revealed that BSP hydrogel had good biocompatibility and biodegradability. Finally, we evaluated the in vivo wound repair effect of BSP hydrogel, and the results showed that BSP hydrogel had a significant wound-healing effect. Furthermore, the BSP hydrogel promoted the polarization of M1-type macrophages towards the M2-type and reduced the inflammatory response during the wound healing phase. Because of its ease of production, safety, efficacy, and environmental friendliness, BSP hydrogel is considered a highly promising material for wound dressings.
Asunto(s)
Hidrogeles , Compuestos Orgánicos , Hidrogeles/farmacología , Compuestos Orgánicos/farmacología , Polisacáridos/química , Cicatrización de HeridasRESUMEN
The expeditious healing of chronic wounds with bacterial infections poses a formidable challenge in clinical practice because of the persistent bacterial presence, excessive inflammation, and the accumulation of reactive oxygen species (ROS) in clinical practice. Thus, in this study, natural antimicrobial material microneedles (MNs) with multifunctional properties were prepared by adding peony leaf extract (PLE) into a matrix of methacrylated Bletilla striata polysaccharide (BSPMA) and methacrylated chitosan (CSMA) via cross-linking under ultra-violet light to accelerate the rapid healing of chronic wounds with bacterial infections. Results showed that BCP-MNs effectively inhibited the growth of Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) by disrupting bacterial cell membranes and accelerated the healing of infected wounds by enhancing cell migration, epidermal regeneration, pro-collagen deposition, and angiogenesis and reducing inflammation. Furthermore, BCP-MNs not only possessed good mechanical properties, stability, and biocompatibility but also showed potent antioxidant effects to eliminate excessive ROS accumulation in the wound bed. In conclusion, BCP-MNs possess multifunctional wound-healing properties and can serve as excellent wound dressing in to treat infected wounds.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Especies Reactivas de Oxígeno , Vendajes , Escherichia coli , Inflamación , Antibacterianos , HidrogelesRESUMEN
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Humanos , Administración Cutánea , Piel , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Inflamación/tratamiento farmacológico , Sistemas de Liberación de MedicamentosRESUMEN
The oral delivery of nano-drug delivery systems (Nano-DDS) remains a challenge. Taking inspirations from viruses, here we construct core-shell mesoporous silica nanoparticles (NPs, ~80 nm) with virus-like nanospikes (VSN) to simulate viral morphology, and further modified VSN with L-alanine (CVSN) to enable chiral recognition for functional bionics. By comparing with the solid silica NPs, mesoporous silica NPs and VSN, we demonstrate the delivery advantages of CVSN on overcoming intestinal sequential barriers in both animals and human via multiple biological processes. Subsequently, we encapsulate indomethacin (IMC) into the nanopores of NPs to mimic gene package, wherein the payloads are isolated from bio-environments and exist in an amorphous form to increase their stability and solubility, while the chiral nanospikes multi-sited anchor and chiral recognize on the intestinal mucosa to enhance the penetrability and ultimately improve the oral adsorption of IMC. Encouragingly, we also prove the versatility of CVSN as oral Nano-DDS.
Asunto(s)
Portadores de Fármacos , Nanopartículas , Animales , Humanos , Indometacina , Solubilidad , Dióxido de Silicio , Porosidad , Sistemas de Liberación de MedicamentosRESUMEN
Inspired by the unique pharmacological effects of chiral drugs in the asymmetrical body environments, it is assumed that the chirality of nanocarriers is also a key factor to determine their oral adsorption efficiency, apart from their size, shape, etc. Herein, l/d-tartaric acid modified mesoporous silica nanoparticles (l/d-CMSNs) are fabricated via a one-pot cocondensation method, and focused on whether the oral adsorption of nanocarriers will be benefited from their chirality. It is found that l-CMSN performed better in the sequential oral absorption processes, including mucus permeation, mucosa bio-adhesion, cellular uptake, intestinal transport and gastrointestinal tract (GIT) retention, than those of the d-chiral (d-CMSN), racemic (dl-CMSN), and achiral (MSN) counterparts. The multiple chiral recognition mechanisms are experimentally and theoretically demonstrated following simple differential adsorption on biointerfaces, wherein electrostatic interaction is the dominant energy. During the oral delivery task, l-CMSN, which is proven to be stable, nonirritative, biocompatible, and biodegradable, is efficiently absorbed into the blood (1.72-2.05-fold higher than other nanocarriers), and helps the loaded doxorubicin (DOX) to achieve better intestinal transport (2.32-27.03-times higher than other samples), satisfactory bioavailability (449.73%) and stronger antitumor effect (up to 95.43%). These findings validated the dominant role of chirality in determining the biological fate of nanocarriers.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , Portadores de Fármacos , Dióxido de Silicio , Estereoisomerismo , Doxorrubicina , PorosidadRESUMEN
Conventional wound dressings fail to satisfy the requirements and needs of wounds in various stages. It is challenging to develop a multifunctional dressing that is hemostatic, antibacterial, anti-inflammatory, and promotes wound healing. Therefore, this study aimed to develop a multifunctional sponge dressing for the full-stage wound healing based on copper and two natural products, Bletilla striata polysaccharide (BSP) and peony leaf extract (PLE). The developed BSP-Cu-PLE sponges were characterized by SEM, XRD, FTIR, and XPS to assess micromorphology and elemental composition. Their properties and bioactivities were also verified by the further experiments, whereby the findings revealed that the BSP-Cu-PLE sponges had improved water absorption and porosity while exhibiting excellent antioxidative, biocompatible, and biodegradable properties. Moreover, the antibacterial test revealed that BSP-Cu-PLE sponges had superior antibacterial activity against S. aureus and E. coli. Furthermore, the hemostatic activity of BSP-Cu-PLE sponges was significantly enhanced in a rat liver trauma model. Most notably, further studies have demonstrated that the BSP-Cu-PLE sponges could significantly (p < 0.05) accelerate the healing process of skin wounds by stimulating collagen deposition, promoting angiogenesis, and decreasing inflammatory cells. In summary, the BSP-Cu-PLE sponges could provide a new strategy for application in clinical setting for full-stage wound healing.
Asunto(s)
Hemostáticos , Paeonia , Ratas , Animales , Cobre , Escherichia coli , Staphylococcus aureus , Cicatrización de Heridas , Polisacáridos/farmacología , Hemostáticos/farmacología , Vendajes , Antibacterianos/farmacologíaRESUMEN
The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores, prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that DOX@CS-CMSN was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo. Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy.
Asunto(s)
Quitosano , Nanopartículas , Neoplasias , Humanos , Dióxido de Silicio , Doxorrubicina/farmacología , Concentración de Iones de Hidrógeno , Microambiente TumoralRESUMEN
Considering the problem of food perishability and the environmental pollution of plastic packaging, the natural active packaging prepared by incorporating plant leaf (e.g. peony leaf) extract into biodegradable food packaging materials may be a key to addressing these issues. In the study, a novel green bioactive composite film (CS-PLE) with antioxidant and antibacterial propertiese was developed by blending peony leaf extract (PLE) into chitosan (CS) film through the solution casting method. The physical properties and biological activities of a series of films, including CS film and CS-PLEs incorporated with different concentrations of PLE, were studied by appropriate experimental protocols. The results demonstrated that addition of PLE improved thermal stability, the barrier performance of UV-A and total phenolic content of CS film, and the antioxidant activities of CS-PLEs increased by 60.6 % ~ 73.2 % with the appending proportion of PLE from 0.1 wt% ~ 0.7 wt% compared to CS film. Furthermore, CS-PLEs had better inhibiting effect on bacteria. Notably, CS-PLE (0.7 wt%) wrapping apples showed the least degree of browning among all the groups. Hence, the study of CS-PLEs can provide a new strategy for the preparation of food packaging materials that are green alternatives and reduce environmental pollution.
Asunto(s)
Quitosano , Paeonia , Embalaje de Alimentos/métodos , Antioxidantes/farmacología , Extractos Vegetales/farmacologíaRESUMEN
In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
RESUMEN
Nano-drug delivery systems (nano-DDSs) with an existing specific interaction to tumor cells and intelligent stimulus-triggered drug delivery performance in a tumor microenvironment (TME) remain hotspots for effective cancer therapy. Herein, multifunctional pH/H2O2 dual-responsive chiral mesoporous silica nanorods (HA-CD/DOX-PCMSRs) were creatively constructed by first grafting phenylboronic acid pinacol ester (PBAP) onto the amino-functioned nanorods, then incorporating doxorubicin (DOX) into the mesoporous structure, and finally coating with the cyclodextrin-modified hyaluronic acid conjugate (HA-CD) through a weak host-guest interaction. Under a physiological environment, the gatekeeper CD could avoid the premature leakage of DOX and minimize the side effects to normal cells. After the uptake by the tumor cells, the H2O2-sensitive moieties of PBAP were exposed and a small amount of DOX was leaked along with the shift of the supramolecular switch HA-CD under the acidic condition. Notably, the self-supplying H2O2 mediated by the released DOX in turn accelerated the PBAP disintegration, further promoted the rapid release of DOX, and increased the DOX accumulation in tumor regions. Innovatively, this nano-DDS could simultaneously achieve the tumor-targeting ability via CD44 receptor-mediated endocytosis and pH/H2O2 dual responsiveness activated by the TME and hence exhibited superior antitumor efficacy. Furthermore, HA acting as the hydrophilic shell could improve the biocompatibility of this nano-DDS.
Asunto(s)
Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Nanotubos/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Ácidos Borónicos/química , Ácidos Borónicos/metabolismo , Ácidos Borónicos/toxicidad , Línea Celular Tumoral , Ciclodextrinas/química , Ciclodextrinas/toxicidad , Doxorrubicina/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/análogos & derivados , Ácido Hialurónico/metabolismo , Ácido Hialurónico/toxicidad , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Ratones Endogámicos BALB C , Nanotubos/toxicidad , Neoplasias/metabolismo , Porosidad , Dióxido de Silicio/química , Dióxido de Silicio/toxicidadRESUMEN
The purpose of this study was to investigate the delivery of poorly water-soluble non-steroidal anti-inflammatory drugs (NSAIDs) by carboxyl-functionalized mesoporous silica nanoparticles (MSN-COOH) with high specific surface area (SBET). In this study, MSN-COOH was prepared by collaborative self-assembly using cetyltrimethylammonium bromide (CTAB) as template and hydrolysis (3-triethoxyl-propyl) succinic anhydride (TESPSA) as co-structure auxiliary directing agent (CSDA). The drug delivery systems were constructed with NSAIDs including Nimesulide (NMS) and Indomethacin (IMC) as model drugs. Moreover, the characterization techniques, hemolysis and bio-adsorption testes, in vitro drug release and in vivo biological studies of MSN-COOH were also carried out. The characterization results showed that MSN-COOH is spheres with clearly visible irregular honeycomb nanopores and rough surface (SBET: 1257 m2/g, pore volume (VP): 1.17 cm3/g). After loading NMS/IMC into MSN-COOH with high drug loading efficiency (NMS: 98.7 and IMC: 98.2%), most crystalline NMS and IMC converted to amorphous phase confirmed using differential scanning calorimeter (DSC) and X-ray power diffraction (XRD) analysis. Meanwhile, MSN-COOH significantly increased the dissolution of NMS and IMC compared with non-functionalized mesoporous silica nanoparticles (MSN), which was also confirmed by wettability experiments. The results of in vivo biological effects showed that MSN-COOH had higher bioavailability of NMS and IMC than MSN, and exerted strong anti-inflammatory effects by delivering more NMS and IMC in vivo. STATEMENT OF SIGNIFICANCE: This study successfully prepared MSNs-COOH (mesoporous silica nanoparticles modified with negatively charged carboxyl groups on the surface and in the pores) with high specific surface area and pore volume by using the negatively charged carboxyl group (hyd-TESPSA) and the positively charged CTAB self-assembled through electrostatic attraction under alkaline conditions. The drug delivery systems were constructed with Nimesulide (NMS) and Indomethacin (IMC) as model drugs. The results showed MSNs-COOH had high drug loading capacity and also exhibited good in vitro drug release properties. Interestingly, NMS loaded MSNs-COOH also had a potential pH responsive release effect. In vivo biological studies revealed that NMS/IMC loaded MSNs-COOH could evidently improve the bioavailability and played the strong anti-inflammatory effects.
Asunto(s)
Nanopartículas , Dióxido de Silicio , Antiinflamatorios no Esteroideos/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Porosidad , AguaRESUMEN
The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120-130 nm with well-developed pore structure (SBET: 1009.94 m2/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.
Asunto(s)
Nanopartículas/química , Nimodipina/farmacocinética , Polietileneimina/química , Dióxido de Silicio/química , Tartratos/química , Administración Oral , Animales , Química Farmacéutica , Portadores de Fármacos/química , Liberación de Fármacos , Masculino , Nimodipina/administración & dosificación , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Solubilidad , Propiedades de SuperficieRESUMEN
Mesoporous silica nanoparticles (MSNs) with remarkable structural features have been proven to be an excellent platform for the delivery of therapeutic molecules. Biological barriers in various forms (e.g., mucosal barrier, cellular barrier, gastrointestinal barrier, blood-brain barrier, and blood-tumor barrier) present substantial obstacles for MSNs. The physicochemical parameters of MSNs are known to be effective and tunable not only for load and release of therapeutic molecules but also for their biological responsiveness that is beneficial for cells and tissues. This review innovatively provides a description of how and why physicochemical properties (e.g., particle size, morphology, surface charge, hydrophilic-hydrophobic property, and surface modification) of MSNs influence their ability to cross the biological barriers prior to reaching targeted sites. First, the structural and physiological features of biological barriers are outlined. Next, the recent progresses in the critical physicochemical parameters of MSNs are highlighted from physicochemical and biological aspects. Surface modification, as an important strategy for achieving rapid transport, is also reviewed with special attention to the latest findings of bioactive groups and molecular mechanisms. Furthermore, advanced designs of multifunction intelligent MSNs to surmount the blood-tumor barrier and to actively target tumor sites are demonstrated in detail. Lastly, the biodegradability and toxicity of MSNs are evaluated. With perspectives for their potential application and biosafety, the clues in summary might lead to drug delivery with high efficiency and provide useful knowledge for rational design of nanomaterials.
Asunto(s)
Nanopartículas , Dióxido de Silicio , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , PorosidadRESUMEN
This study examined the effects of pH and chirality on the release of flurbiprofen (FP)-loaded chiral (L/D) self-assembled mesoporous silica nanoparticles (CSA-L/D-MSNs), which were synthesized using cationic cetyltrimethyl ammonium bromide (CTAB) as a template and chiral modified using L/D-tartaric acids. The morphology and physicochemical properties of the CSA-L/D-MSNs were systemically determined and compared with those of non-functionalized mesoporous silica nanoparticles (MSN). The results showed that the CSA-L/D-MSNs were spherical nanoparticles, and the chirality in the L/D-tartaric acids was successfully imparted to the CSA-L/D-MSNs. FP could be loaded into the CSA-L/D-MSNs and was effectively transformed from the crystalline state to an amorphous state after drug loading due to the finite size effect. The release of FP@CSA-L/D-MSNs was faster than that of FP in a pH 1.2 medium and slower in a pH 6.8 medium, and it was better than that of FP@MSNs in both release mediums. Meanwhile, the FP@CSA-L/D-MSNs exhibited a clearly enhanced pH response because the negatively charged carboxyl groups on their surface induced stronger electrostatic repulsion between FP and CSA-L/D-MSNs. Moreover, the effect of the chiral environment on the release of FP@CSA-L/D-MSNs was further studied by introducing small-molecule chiral additives (L/D-alanine). It was found that the release of FP was inhibited in a chiral environment. Particularly, the CSA-L/D-MSNs began to exert the chiral recognition function, in which the CSA-L-MSN responded to chiral stimuli and enhanced the cumulative release amount from 84.25 %-89.11 % in a pH 6.8-L medium, while the CSA-D-MSN showed a suppressed release in the pH 6.8-L medium. Notably, the CSA-L/D-MSNs exhibited intelligent drug release by both chirality response and pH response, and will provide valuable guidance for the design of drug delivery systems.
Asunto(s)
Flurbiprofeno , Nanopartículas , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Porosidad , Dióxido de SilicioRESUMEN
PURPOSE: The aim of this study was to improve the oral bioavailability and anti-inflammatory activity of the poorly soluble drug ibuprofen (IBU) by employing a new kind of poly(ethyleneimine)s (PEIs)-based mesocellular siliceous foam (MSF) called B-BMSF@PEI as drug carrier. METHODS: B-BMSF@PEI was biomimetically synthesized by using PEIs as templates, catalysts and scaffolds under ambient conditions, and the structural characteristics, including size, morphology, mesoscopic structure and pore properties, were estimated by TEM, SEM, FTIR and N2 desorption/adsorption measurement. Then, IBU was incorporated into B-BMSF@PEI at the drug:carrier weight ratio of 1:1. The structural features of IBU before and after drug loading were systemically characterized. IBU and B-BMSF@PEI were then subject to in vitro drug release study and wettability analysis. Finally, in vivo pharmacokinetics and anti-inflammatory pharmacodynamics studies were carried out to evaluate the efficacy of B-BMSF@PEI on improving the oral adsorption of IBU. RESULTS: The results demonstrated that B-BMSF@PEI was a meso-meso porous silica material with foam appearance. It consisted of uniform spherical cells (40 nm) with interconnected pore networks. IBU can be successfully loaded into B-BMSF@PEI with high efficiency (as high as 39.53%), and crystal IBU was effectively converted to an amorphous state during this process. Benefiting from the great architectures of B-BMSF@PEI, IBU/B-BMSF@PEI performed good wetting property and significantly improved the dissolution rate in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Notably, IBU exhibited very satisfactory relative bioavailability (681.4%) and anti-inflammatory effects (the inhibition rates were between the ranges of 113.5% to 1504.3%). CONCLUSION: B-BMSF@PEI with bimodal mesoporous system and interconnected nanopores was obtained owing to the dynamic self-assembly functions of PEIs. It had superiority in drug loading and could improve the oral adsorption of ibuprofen to a satisfactory level.