RESUMEN
Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.
Asunto(s)
Materiales Biocompatibles/uso terapéutico , Inmunoterapia , Neoplasias/terapia , Materiales Biocompatibles/química , Humanos , Nanopartículas/química , Neoplasias/inmunologíaRESUMEN
The extracellular matrix microenvironment of bone tissue comprises several physiological cues. Thus, artificial bone substitute materials with a single cue are insufficient to meet the demands for bone defect repair. Regeneration of critical-size bone defects remains challenging in orthopedic surgery. Intrinsic viscoelastic and piezoelectric cues from collagen fibers play crucial roles in accelerating bone regeneration, but scaffolds or implants providing integrated cues have seldom been reported. In this study, it is aimed to design and prepare hierarchically porous poly(methylmethacrylate)/polyethyleneimine/poly(vinylidenefluoride) composite implants presenting a similar viscoelastic and piezoelectric microenvironment to bone tissue via anti-solvent vapor-induced phase separation. The viscoelastic and piezoelectric cues of the composite implants for human bone marrow mesenchymal stem cell line stimulate and activate Piezo1 proteins associated with mechanotransduction signaling pathways. Cortical and spongy bone exhibit excellent regeneration and integration in models of critical-size bone defects on the knee joint and femur in vivo. This study demonstrates that implants with integrated physiological cues are promising artificial bone substitute materials for regenerating critical-size bone defects.
Asunto(s)
Sustitutos de Huesos , Andamios del Tejido , Humanos , Osteogénesis , Sustitutos de Huesos/farmacología , Porosidad , Mecanotransducción Celular , Regeneración Ósea , Ingeniería de TejidosRESUMEN
In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.5 mV at 37 degrees C, and could efficiently transfer pGFP into HEK293 cells in vitro. Meanwhile, as a model hydrophobic chemotherapeutic drug, honokiol was loaded into PCEC-g-PEI micelles by direct dissolution method assisted by ultrasonication. The honokiol loaded cationic PCEC-g-PEI micelles could effectively adsorb DNA onto its surface, while it could release honokiol in an extended period in vitro. This study demonstrated a novel DNA and hydrophobic chemotherapeutic drug co-delivery system.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Técnicas de Transferencia de Gen , Micelas , Nanoconjugados/química , Poliésteres/química , Polietilenglicoles/química , Polietileneimina/química , Compuestos de Bifenilo/farmacocinética , Supervivencia Celular , ADN/administración & dosificación , ADN/química , ADN/genética , Células HEK293 , Humanos , Lignanos/farmacocinética , Tamaño de la Partícula , TemperaturaRESUMEN
In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro. Otherwise, the immunogenicity of bFGF was improved significantly after encapsulated into the hydrogel. Strong humoral immunity created by bFGF-hydrogel was maintained for more than 14 weeks. Therefore, the prepared bFGF loaded PECE hydrogel might have great potential as a novel vaccine adjuvant for protein antigen.
Asunto(s)
Antígenos , Sistemas de Liberación de Medicamentos , Factor 2 de Crecimiento de Fibroblastos , Hidrogel de Polietilenoglicol-Dimetacrilato , Poliésteres , Polietilenglicoles , Animales , Anticuerpos/sangre , Antígenos/administración & dosificación , Antígenos/inmunología , Materiales Biocompatibles , Preparaciones de Acción Retardada , Femenino , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/inmunología , Calor , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/administración & dosificación , Hidrogel de Polietilenoglicol-Dimetacrilato/toxicidad , Inmunidad Humoral , Inyecciones , Células L , Ratones , Ratones Endogámicos BALB C , Poliésteres/administración & dosificación , Poliésteres/toxicidad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/toxicidad , Vacunas/administración & dosificación , Vacunas/inmunologíaRESUMEN
BACKGROUND: Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy. RESULTS: A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 microg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate. CONCLUSION: The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.
Asunto(s)
Materiales Biocompatibles/farmacocinética , Sistemas de Liberación de Medicamentos , Hidrogeles/farmacocinética , Poloxámero/farmacología , Poliésteres/farmacocinética , Polietilenglicoles/farmacocinética , Compuestos de Bifenilo/farmacocinética , Línea Celular , Supervivencia Celular , Humanos , Lignanos/farmacocinética , Temperatura , Vitamina B 12/farmacocinéticaRESUMEN
Drug resistance and recurrence are the main clinical challenges in chemotherapy of lymphoma. Methotrexate (MTX), especially high dose MTX (HD MTX), is extensively used to treat some aggressive subtypes of lymphoma, such as Burkitt's lymphoma, in order to overcome drug resistance. But poor solubility of the free drug and severe side effects of HD MTX limit its clinical application. Polymeric micelle, as an ideal nano delivery system, provides effective solutions to these problems. In this work, monomethyl poly (ethylene glycol)-poly (ε-caprolactone) (MPEG-PCL) was employed to load MTX through a one-step solid dispersion method. MTX loaded micelles had a small particle size of 25.64⯱â¯0.99â¯nm and polydisperse index (PDI) of 0.176⯱â¯0.05. Drug loading and encapsulation efficiency of MTX loaded micelles were 5.57⯱â¯0.14% and 92.46⯱â¯2.38%. Compared with free MTX, MTX loaded micelles demonstrated a much slower and sustained release behavior in vitro. MTT assay and cell apoptosis study suggested that MTX loaded micelles were more effective in inhibiting proliferation and inducing apoptosis on Raji lymphoma cells than MTX injection, which was especially distinct in high dose groups. Cellular uptake study indicated that MPEG-PCL micelle had a 1.5 times higher uptake rate in Raji cells. As for in vivo studies, MTX loaded micelles were more competent to suppress tumor growth and prolong survival time than MTX injection in the subcutaneous Raji lymphoma model. Notably, the high dose group of micelle formulation exhibited the strongest anti-tumor effect without additional toxicity. Furthermore, immunofluorescent and immunohistochemical studies showed that tumors of MPEG-PCL-MTX treated mice had more apoptotic cells and fewer proliferative cells. In conclusion, MPEG-PCL-MTX micelle is an excellent intravenously injectable formulation of MTX with both good solubility and enhanced anti-tumor activity, which perfectly meets clinical demands, especially for administration of HD MTX.
Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Linfoma/tratamiento farmacológico , Micelas , Poliésteres/administración & dosificación , Polietilenglicoles/administración & dosificación , Animales , Antineoplásicos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Femenino , Humanos , Inyecciones Intravenosas , Linfoma/patología , Ratones SCID , Poliésteres/química , Polietilenglicoles/química , Carga Tumoral/efectos de los fármacosRESUMEN
A series of biodegradable PCL-PEG-PCL block copolymers were successfully synthesized by ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene glycol) (PEG), which were characterized by (1)H NMR, (13)C NMR, and FTIR. Their aqueous solution displayed special gel-sol transition behavior with temperature increasing from 4 to 100 degrees C, when the polymer concentration was above corresponding critical gel concentration (CGC). The gel-sol phase diagram was recorded using test tube inverting method and DSC method, which depended not only on chemical composition of copolymers, but also on heating history of copolymer's aqueous solution. As a result, the gel-sol transition temperature could be adjusted, which might be very useful for its application in biomedical fields such as injectable drug delivery system. And the typical shell-core structure of PCL-PEG-PCL micelles was introduced. The micelle-packing and partial crystallization might be the key gelation machanism for this gel-sol transition behavior of PCL-PEG-PCL aqueous solution.
Asunto(s)
Implantes Absorbibles , Materiales Biocompatibles/química , Poliésteres/química , Polietilenglicoles/química , Rastreo Diferencial de Calorimetría , Geles , Calor , Espectroscopía de Resonancia Magnética , Micelas , Peso Molecular , Soluciones , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Despite advantageous properties, micelles using methoxy poly(ethylene glycol)-poly(trimethylene carbonate) (MPEGPTMC) have not been widely studied. In this work, we aim to develop a novel vehicle for vincristine (VCR) based on a MPEG-PTMC micelle system. MPEG-PTMC with a series of molecular weights were synthesized and screened for the appropriate range for forming stable VCR micelles. The prepared micelles were then characterized in vitro and in vivo . VCR micelles presented high stability and ideal sustained release profile. The passive targeting effect was also enhanced compared with liposomal VCR. These results provide critical data to give the first clues regarding novel VCR micelles which exhibit potential for clinical application.
Asunto(s)
Implantes Absorbibles , Dioxanos/química , Implantes de Medicamentos/química , Nanocápsulas/química , Polietilenglicoles/química , Vincristina/administración & dosificación , Vincristina/química , Cristalización/métodos , Difusión , Composición de Medicamentos/métodos , Implantes de Medicamentos/administración & dosificación , Micelas , Nanocápsulas/administración & dosificaciónRESUMEN
BACKGROUND: Poly(ether-ether) and poly(ether-ester) block copolymers have been widely applied in biomedical fields over two decades due to their good safety and biocompatibility. Poly(ethylene glycol), poly(ethylene glycol)-poly(propylene glycol) and poly(lactic-co-glycolic acid) have been approved as excipients by Food and Drug Administration. Because of the broad perspective in biomedical fields, many novel poly(etherether) and poly(ether-ester) block copolymers have been developed for drug delivery, gene therapy and tissue engineering in recent years. This review focuses on active targeting theranostic systems, gene delivery systems and tissue engineering based on poly(ether-ether) and poly(ether-ester) block copolymers. METHODS: We perform a structured search of bibliographic databases for peer-reviewed scientific reports using a focused review question and inclusion/exclusion criteria. The literatures related to the topics of this review are cataloged according to the developed copolymers or their applications such as active targeting theranostic systems, gene delivery systems and tissue engineering. Some important advances and new trends are summarized in this review. RESULTS: Some commercial poly(ether-ether) copolymers have been used as excipients for drug research and development. Amphiphilic and biodegradable poly(ether-ester) diblock copolymers are capable of formulating biomedical nanoparticulate theranostic systems, and targeting moiety-functionalized poly(ether-ester) diblock copolymers will be further developed and applied in biomedical nanotechnology fields in the near future. Meanwhile, triblock or multiblock poly(ether-ether) and poly(ether-ester) copolymers with environmentsensitive properties are suitable for gene delivery and tissue engineering. Poly(ether-ether) and poly(ether-ester) copolymers are being extensively applied in active targeting theranostic systems, gene delivery systems and tissue engineering. CONCLUSIONS: Biodegradable, environment-sensitive and targeting moiety-functionalized block copolymers, which are being applied in active targeting theranostic systems, gene delivery systems and tissue engineering, are promising candidates for treatment of various diseases.
Asunto(s)
Materiales Biocompatibles/química , Éter/química , Poliésteres/química , Polímeros/química , Excipientes/química , Técnicas de Transferencia de Gen , HumanosRESUMEN
In this study, a series of injectable thermoreversible and thermogelling PDLLA-PEG-PDLLA copolymers were developed and a systematic evaluation of the thermogelling system both in vitro and in vivo was performed. The aqueous PDLLA-PEG-PDLLA solutions above a critical gel concentration could transform into hydrogel spontaneously within 2 minutes around the body temperature in vitro or in vivo. Modulating the molecular weight, block length and polymer concentration could adjust the sol-gel transition behavior and the mechanical properties of the hydrogels. The gelation was thermally reversible due to the physical interaction of copolymer micelles and no crystallization formed during the gelation. Little cytotoxicity and hemolysis of this polymer was found, and the inflammatory response after injecting the hydrogel to small-animal was acceptable. In vitro and in vivo degradation experiments illustrated that the physical hydrogel could retain its integrity as long as several weeks and eventually be degraded by hydrolysis. A rat model of sidewall defect-bowel abrasion was employed, and a significant reduction of post-operative adhesion has been found in the group of PDLLA-PEG-PDLLA hydrogel-treated, compared with untreated control group and commercial hyaluronic acid (HA) anti-adhesion hydrogel group. As such, this PDLLA-PEG-PDLLA hydrogel might be a promising candidate of injectable biomaterial for medical applications.
Asunto(s)
Hidrogeles/química , Hidrogeles/síntesis química , Poliésteres/química , Poliésteres/síntesis química , Polietilenglicoles/química , Polietilenglicoles/síntesis química , Temperatura , Animales , Materiales Biocompatibles/farmacología , Modelos Animales de Enfermedad , Femenino , Inyecciones Subcutáneas , Ratones Endogámicos BALB C , Micelas , Peritoneo/efectos de los fármacos , Peritoneo/patología , Transición de Fase , Ratas Sprague-Dawley , Reología , Adherencias Tisulares/prevención & controlRESUMEN
Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.
Asunto(s)
Neoplasias Ováricas/terapia , Animales , Línea Celular Tumoral , Femenino , Terapia Genética , Humanos , Liposomas , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Ováricas/patología , Plásmidos/genética , Transfección , Vesiculovirus/genética , Proteínas de la Matriz Viral/genéticaRESUMEN
Poly(ethylene glycol)-cholesterol (PEG-Chol) conjugates are composed of "hydrophilically-flexible" PEG and "hydrophobically-rigid" Chol molecules. PEG-Chol conjugates are capable of forming micelles through molecular self-assembly and they are also used extensively for the PEGylation of drug delivery systems (DDS). The PEGylated DDS have been shown to display optimized physical stability properties in vitro and longer half-lives in vivo when compared with non-PEGylated DDS. Cell uptake studies have indicated that PEG-Chol conjugates are internalized via clathrin-independent pathways into endosomes and Golgi apparatus. Acid-labile PEG-Chol conjugates are also able to promote the content release of PEGylated DDS when triggered by dePEGylation at acidic conditions. More importantly, biodegradable PEG-Chol molecules have been shown to decrease the "accelerated blood clearance" phenomenon of PEG-DSPE. Ligands, peptides or antibodies which have been modified with PEG-Chols are oftentimes used to formulate active targeting DDS, which have been shown in many systems recently to enhance the efficacy and lower the adverse effects of drugs. Production of PEG-Chol is simple and efficient, and production costs are relatively low. In conclusion, PEG-Chol conjugates appear to be very promising multifunctional biomaterials for many uses in the biomedical sciences and pharmaceutical industries.
Asunto(s)
Colesterol/análogos & derivados , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/tendencias , Preparaciones Farmacéuticas/química , Polietilenglicoles/química , Animales , Transporte Biológico , Membrana Celular/metabolismo , Química Farmacéutica/tendencias , Colesterol/química , Técnicas de Transferencia de Gen/tendencias , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Preparaciones Farmacéuticas/metabolismo , Tecnología Farmacéutica/tendenciasRESUMEN
Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.
Asunto(s)
Abdomen/cirugía , Implantes Absorbibles , Hidrogeles/uso terapéutico , Polietilenglicoles/uso terapéutico , Adherencias Tisulares/prevención & control , Técnicas de Cierre de Herida Abdominal/efectos adversos , Animales , Enfermedades del Ciego/prevención & control , Ciego , Evaluación Preclínica de Medicamentos , Femenino , Hidrogeles/química , Hidrogeles/farmacocinética , Enfermedades Peritoneales/prevención & control , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , TemperaturaRESUMEN
Postsurgical peritoneal adhesion is a major concern in clinical practice which causes significant morbidity and mortality. In this study, we investigated the efficacy of biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) micelles in preventing postsurgical cauterization-induced peritoneal adhesion. The biodegradable PEG-PCL-PEG copolymer could form nano-sized micelles in water, which instantly turned into a non-flowing gel at body temperature due to micellar aggregation. Moreover, a novel sidewall and cecum cauterization rat model was developed and the micelles were assigned for adhesion prevention tests. The PEG-PCL-PEG micelles could be administered by an ordinary syringe and provided unrestricted coverage of the cauterized peritoneum. The micelles instantly formed a gel in situ at body temperature and the formed gel could adhere to the cauterized sites as a durable barrier during critical time of adhesion formation. All rats from the control group (n = 10) developed score 5 adhesion, whereas, eight out of ten rats in the micelle-treated group showed no adhesion at all. Besides, cauterization-induced adhesion formation, adhesiveness and degradation of micelles, remesothelization of peritoneum, and restoration of cauterized tissue were investigated in detail. Our results thus indicated that, it was feasible to use biodegradable and injectable thermosensitive PEG-PCL-PEG micelles for prevention of peritoneal adhesions after surgery.
Asunto(s)
Implantes Absorbibles , Cauterización/efectos adversos , Micelas , Enfermedades Peritoneales/prevención & control , Poliésteres/uso terapéutico , Polietilenglicoles/uso terapéutico , Adherencias Tisulares/prevención & control , Animales , Cauterización/métodos , Femenino , Ensayo de Materiales , Ratones , Células 3T3 NIH , Peritoneo/efectos de los fármacos , Peritoneo/cirugía , Poliésteres/farmacocinética , Poliésteres/farmacología , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Ratas , Ratas Wistar , Temperatura , Resultado del TratamientoRESUMEN
Luteolin (Lu) is one of the flavonoids with anticancer activity, but its poor water solubility limits its use clinically. In this work, we used monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles to encapsulate Lu by a self-assembly method, creating a water-soluble Lu/MPEG-PCL micelle. These micelles had a mean particle size of 38.6 ± 0.6 nm (polydispersity index = 0.16 ± 0.02), encapsulation efficiency of 98.32% ± 1.12%, and drug loading of 3.93% ± 0.25%. Lu/MPEG-PCL micelles could slowly release Lu in vitro. Encapsulation of Lu in MPEG-PCL micelles improved the half-life (t½ ; 152.25 ± 49.92 versus [vs] 7.16 ± 1.23 minutes, P = 0.007), area under the curve (0-t) (2914.05 ± 445.17 vs 502.65 ± 140.12 mg/L/minute, P = 0.001), area under the curve (0-∞) (2989.03 ± 433.22 vs 503.81 ± 141.41 mg/L/minute, P = 0.001), and peak concentration (92.70 ± 11.61 vs 38.98 ± 7.73 mg/L, P = 0.003) of Lu when the drug was intravenously administered at a dose of 30 mg/kg in rats. Also, Lu/MPEG-PCL micelles maintained the cytotoxicity of Lu on 4T1 breast cancer cells (IC50 = 6.4 ± 2.30 µg/mL) and C-26 colon carcinoma cells (IC50 = 12.62 ± 2.17 µg/mL) in vitro. These data suggested that encapsulation of Lu into MPEG-PCL micelles created an aqueous formulation of Lu with potential anticancer effect.
Asunto(s)
Antineoplásicos/química , Luteolina/química , Micelas , Poliésteres/química , Polietilenglicoles/química , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Luteolina/sangre , Luteolina/farmacocinética , Luteolina/farmacología , Ratones , Nanopartículas/química , Ratas , Ratas Sprague-Dawley , SolubilidadRESUMEN
Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/síntesis química , Neoplasias Pulmonares/tratamiento farmacológico , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Poliésteres/química , Polietilenglicoles/química , Animales , Línea Celular Tumoral , Curcumina/administración & dosificación , Curcumina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Femenino , Inyecciones Intravenosas , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Micelas , Nanocápsulas/ultraestructura , Tamaño de la Partícula , Resultado del TratamientoRESUMEN
The biodegradable polylactide/poly(ethylene glycol) (PLA/PEG) hybrid membranes were fabricated via electrospinning of PLA/PEG solution. Their structures and properties were investigated by scanning electron microscopy, differential scanning calorimetry, and water contact angle. In vitro hydrolytic degradation showed that PEG content influenced the degradation rate of the PLA/PEG hybrid mats. The mechanical property was measured by tensile test and the result revealed that the addition of PEG had an obvious plasticization on PLA matrix. In-vitro biocompatibility was investigated by culturing cell on the scaffolds and MTT assay. The results indicated that the cell could attach and proliferate on the membranes, so confirmed that the PLA/PEG hybrid membrane had good biocompatibility, and it could be a promising biomaterial for tissue engineering applications.
Asunto(s)
Polietilenglicoles/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Rastreo Diferencial de Calorimetría , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hidrólisis , Ratones , Células 3T3 NIH , Estrés Mecánico , Temperatura , Resistencia a la Tracción/efectos de los fármacos , Agua/químicaRESUMEN
The need to enhance the immunogenicity of tumor-associated antigens and modulate the resulting immune responses has prompted the development of new adjuvants. We prepared a novel adjuvant, lipopolysaccharides (LPS) loaded thermosensitive hydrogel (LPS-Hydrogel), for truncated basic fibroblast growth factor (tbFGF) peptide to enhance immunological responses and improve therapeutic effects in cancer. When co-formulated with tbFGF, LPS-Hydrogel formed antigen-adjuvant complexes, which enhanced antibody and cell-mediated responses in mice, thus promoting a more balanced antibody-mediated and cytotoxic T lymphocyte (CTL)-mediated immune response to inhibit tumor growth and metastases in vivo. Furthermore, the secretion of IFN-γ and IL-4 was detected, confirming activation of the two immune responses in vivo. There were no significant systemic toxicities observed with tbFGF-LPS-Hydrogel treatment. These results suggested that the thermosensitive and biodegradable LPS-Hydrogel was a novel adjuvant and carrier for peptide vaccines in cancer immunotherapy.
Asunto(s)
Adyuvantes Inmunológicos , Carcinoma Pulmonar de Lewis , Factor 2 de Crecimiento de Fibroblastos , Hidrogel de Polietilenoglicol-Dimetacrilato , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Lipopolisacáridos , Adyuvantes Inmunológicos/síntesis química , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Animales , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Factor 2 de Crecimiento de Fibroblastos/química , Factor 2 de Crecimiento de Fibroblastos/farmacología , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Interferón gamma/inmunología , Interleucina-4/inmunología , Lipopolisacáridos/química , Lipopolisacáridos/farmacología , Ratones , Células 3T3 NIH , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
In orthopedic tissue engineering, the extensively applied acellular bone matrix (ABM) can seldom be prefabricated just right to mold the cavity of the diverse defects, might induce severe inflammation on account of the migration of small granules and usually bring the patients great pain in the treatment. In this study, a new injectable thermosensitive ABM/PECE composite with good biocompatibility was designed and prepared by adding the ABM granules into the triblock copolymer poly(ethylene eglycol)-poly(ε-caprolactone)-poly(ethylene eglycol) (PEG-PCL-PEG, PECE). The PECE was synthesized by ring-opening copolymerization and characterized by ¹H NMR. The ABM was prepared by acellular treatment of natural bone and ground to fine granules. The obtained ABM/PECE composite showed the most important absorption bands of ABM and PECE copolymer in FT-IR spectroscopy and underwent sol-gel phage transition from solution to nonflowing hydrogel at 37°C. SEM results indicated that the ABM/PECE composite with different ABM contents all presented similar porous 3D structure. ABM/PECE composite presented mild cytotoxicity to rat MSCs in vitro and good biocompatibility in the BALB/c mice subcutis up to 4 weeks. In conclusion, all the results confirmed that the injectable thermosensitive ABM/PECE composite was a promising candidate for orthopedic tissue engineering in a minimally-invasive way.
Asunto(s)
Materiales Biocompatibles/farmacología , Matriz Ósea/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Poliésteres/síntesis química , Poliésteres/farmacología , Polietilenglicoles/síntesis química , Polietilenglicoles/farmacología , Temperatura , Animales , Matriz Ósea/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Humanos , Inyecciones , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Rastreo , Transición de Fase/efectos de los fármacos , Poliésteres/química , Poliésteres/toxicidad , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Ratas , Ratas Sprague-Dawley , Reología/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Tejido Subcutáneo/efectos de los fármacos , Tejido Subcutáneo/patologíaRESUMEN
Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(É-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy.