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1.
J Transl Med ; 22(1): 341, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594751

RESUMO

BACKGROUND: Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. METHODS: Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. RESULTS: This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. CONCLUSIONS: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Camundongos , Animais , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Imiquimode/farmacologia , Imiquimode/uso terapêutico , Morte Celular Imunogênica , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodos , Imunidade , Microambiente Tumoral
2.
Biomed Pharmacother ; 173: 116389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461682

RESUMO

Staphylococcus aureus is one of the most common bacterial isolates found in wounds. Thus, innovative dressings, such as hydrogels, are interesting vehicles for incorporating bioactive compounds like those from Melaleuca alternifolia essential oil (MaEO). In this study, we evaluated the antimicrobial and anti-inflammatory potential of MaEO incorporated into an alginate and chitosan hydrogel for treating wounds infected by S. aureus. The hydrogel incorporated with MaEO 1% (HMa 1%) was homogeneous with a bright pale-yellow color and the characteristic smell of Melaleuca. The incorporation of MaEO 1% does not affect the stability of the hydrogel, which was stable up to 90 days of storage. The Scanning electron microscopy analysis revealed that hydrogels showed irregular surfaces and interconnected porous structures with accumulations of oil crystals distributed throughout the formulation. HMa 1% has a high moisture content (95.1%) and can absorb simulated wound fluid. Regarding the antimicrobial effects, HMa 1% reduced the growth of S. aureus ATCC 6538 in both in vitro conditions and in an ex vivo model of wounds using porcine skin. In addition, the dairy topical treatment of murine skin lesions with HMa 1% induced a significant reduction of the wound area, inflammation score, and bacterial load, as well as tissue re-epithelialization and modulation of inflammatory mediators. Therefore, hydrogel incorporated with MaEO 1% has excellent potential to be used in the pharmacotherapy of infected wounds.


Assuntos
Anti-Infecciosos , Melaleuca , Óleos Voláteis , Infecções Estafilocócicas , Óleo de Melaleuca , Suínos , Animais , Camundongos , Staphylococcus aureus , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/química , Melaleuca/química , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Anti-Infecciosos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Óleo de Melaleuca/farmacologia , Óleo de Melaleuca/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
3.
Biomed Pharmacother ; 173: 116309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479180

RESUMO

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.


Assuntos
Técnicas Biossensoriais , Acidente Vascular Cerebral , Humanos , Hidrogéis/uso terapêutico , Materiais Biocompatíveis , Engenharia Tecidual , Acidente Vascular Cerebral/tratamento farmacológico
4.
BMC Oral Health ; 24(1): 395, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549147

RESUMO

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.


Assuntos
Perda do Osso Alveolar , Curcumina , Compostos Organometálicos , Periodontite , Piridinas , Ratos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Hidrogéis/uso terapêutico , Modelos Animais de Doenças , Ratos Sprague-Dawley , Periodontite/metabolismo , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/metabolismo , Porphyromonas gingivalis
5.
J Mater Chem B ; 12(12): 2938-2949, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38426380

RESUMO

The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT). However, this procedure may miss small lesions or incompletely remove them, resulting in cancer recurrence or progression. As a result, intravesical instillation of chemotherapy or immunotherapy drugs is often used as an adjunctive treatment after TURBT to prevent cancer recurrence. In the traditional method, drugs are instilled into the patient's bladder through a urinary catheter under sterile conditions. However, this treatment exposes the bladder mucosa to the drug directly, leading to potential side effects like chemical cystitis. Furthermore, this treatment has several limitations, including a short drug retention period, susceptibility to urine dilution, low drug permeability, lack of targeted effect, and limited long-term clinical efficacy. Hydrogel, a polymer material with a high-water content, possesses solid elasticity and liquid fluidity, making it compatible with tissues and environmentally friendly. It exhibits great potential in various applications. One emerging use of hydrogels is in intravesical instillation. By employing hydrogels, drug dilution is minimized, and drug absorption, retention, and persistence in the bladder are enhanced due to the mucus-adhesive and flotation properties of hydrogel materials. Furthermore, hydrogels can improve drug permeability and offer targeting capabilities. This article critically examines the current applications and future prospects of hydrogels in the treatment of bladder cancer.


Assuntos
Hidrogéis , Neoplasias da Bexiga Urinária , Humanos , Hidrogéis/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Sistemas de Liberação de Medicamentos , Administração Intravesical , Resultado do Tratamento
6.
Int J Biol Macromol ; 265(Pt 1): 130901, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490383

RESUMO

This study introduces a starch/PVA/g-C3N4 nanocarrier hydrogel for pH-sensitive DOX delivery in breast cancer. DOX was loaded into the nanocarrier with 44.75 % loading efficiency and 88 % Entrapment Efficiency. The release of DOX from the starch/PVA/g-C3N4 hydrogel was pH-sensitive: DOX was released faster in the acidic environment pertinent to cancer tumors (with a pH level of 5.4) than in the surrounding regular tissue environment carrying a more neutral environment (pH 7.4). The release kinetics analysis, encompassing zero-order, first-order, Higuchi, and Korsmeyer-Peppas models, revealed significant fitting with the Higuchi model at both pH 5.4 (R2 = 0.99, K = 9.89) and pH 7.4 (R2 = 0.99, K = 5.70) levels. Finally, we found that hydrogel was less damaging to healthy cells and more specific to apoptotic cells than the drug's free form. The starch/PVA/g-C3N4 hydrogel had low toxicity for both normal cells and breast cancer cells, whereas DOX loaded into the starch/PVA/g-C3N4 hydrogel had higher toxicity for cancer cells than the DOX-only control samples, and led to specific high apoptosis for cancer cells. The study suggests that DOX can be loaded into a starch/PVA/g-C3N4 hydrogel to improve the specificity of the drug's release in cancer tumors or in vitro breast cancer cells.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Hidrogéis/uso terapêutico , Amido/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Concentração de Íons de Hidrogênio , Portadores de Fármacos/uso terapêutico
7.
Int J Biol Macromol ; 265(Pt 1): 130866, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490390

RESUMO

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.


Assuntos
Algas Comestíveis , Lipopolissacarídeos , Polissacarídeos , Sargassum , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/uso terapêutico , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Peixe-Zebra/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sargassum/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , NF-kappa B/metabolismo
8.
ACS Appl Bio Mater ; 7(3): 1888-1898, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38349328

RESUMO

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.


Assuntos
Exossomos , Alho , Polietilenos , Polipropilenos , Infecções Estafilocócicas , Camundongos , Animais , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Staphylococcus aureus , Peróxido de Hidrogênio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Bandagens , Hidrogéis/uso terapêutico , Hidrogéis/farmacologia
9.
Cells ; 13(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38391976

RESUMO

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.


Assuntos
Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Hidrogéis/uso terapêutico , Liberação Controlada de Fármacos , Temozolomida/uso terapêutico , Impressão Tridimensional , Microambiente Tumoral
10.
J Mater Chem B ; 12(9): 2253-2273, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375592

RESUMO

The injury of both central and peripheral nervous systems can result in neurological disorders and severe nervous diseases, which has been one of the challenges in the medical field. The use of peptide-based hydrogels for nerve repair and regeneration (NRR) provides a promising way for treating these problems, but the effects of the functions of peptide hydrogels on the NRR efficiency have been not understood clearly. In this review, we present recent advances in the material design, matrix fabrication, functional tailoring, and NRR applications of three types of peptide-based hydrogels, including pure peptide hydrogels, other component-functionalized peptide hydrogels, and peptide-modified polymer hydrogels. The case studies on the utilization of various peptide-based hydrogels for NRR are introduced and analyzed, in which the effects and mechanisms of the functions of hydrogels on NRR are illustrated specifically. In addition, the fabrication of medical NRR scaffolds and devices for pre-clinical application is demonstrated. Finally, we provide potential directions on the development of this promising topic. This comprehensive review could be valuable for readers to know the design and synthesis strategies of bioactive peptide hydrogels, as well as their functional tailoring, in order to promote their practical applications in tissue engineering, biomedical engineering, and materials science.


Assuntos
Hidrogéis , Procedimentos de Cirurgia Plástica , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Engenharia Tecidual , Peptídeos/farmacologia , Engenharia Biomédica
11.
Biomacromolecules ; 25(3): 2041-2051, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38380621

RESUMO

Triple-negative breast cancer (TNBC), accounting for approximately 20% of breast cancer cases, is a particular subtype that lacks tumor-specific targets and is difficult to treat due to its high aggressiveness and poor prognosis. Chemotherapy remains the major systemic treatment for TNBC. However, its applicability and efficacy in the clinic are usually concerning due to a lack of targeting, adverse side effects, and occurrence of multidrug resistance, suggesting that the development of effective therapeutics is still highly demanded nowadays. In this study, an injectable alginate complex hydrogel loaded with indocyanine green (ICG)-entrapped perfluorocarbon nanoemulsions (IPNEs) and camptothecin (CPT)-doped chitosan nanoparticles (CCNPs), named IPECCNAHG, was developed for photochemotherapy against TNBC. IPNEs with perfluorocarbon can induce hyperthermia and generate more singlet oxygen than an equal dose of free ICG upon near-infrared (NIR) irradiation to achieve photothermal and photodynamic therapy. CCNPs with positive charge may facilitate cellular internalization and provide sustained release of CPT to carry out chemotherapy. Both nanovectors can stabilize agents in the same hydrogel system without interactions. IPECCNAHG integrating IPNEs and CCNPs enables stage-wise combinational therapeutics that may overcome the issues described above. With 60 s of NIR irradiation, IPECCNAHG significantly inhibited the growth of MDA-MB-231 tumors in the mice without systemic toxicity within the 21 day treatment. We speculate that such anticancer efficacy was accomplished by phototherapy followed by chemotherapy, where cancer cells were first destroyed by IPNE-derived hyperthermia and singlet oxygen, followed by sustained damage with CPT after internalization of CCNPs; a two-stage tumoricidal process. Taken together, the developed IPECCNAHG is anticipated to be a feasible tool for TNBC treatment in the clinic.


Assuntos
Fluorocarbonos , Nanopartículas , Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Hidrogéis/uso terapêutico , Oxigênio Singlete , Fototerapia , Verde de Indocianina/farmacologia , Linhagem Celular Tumoral
12.
J Mater Chem B ; 12(10): 2559-2570, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38362614

RESUMO

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.


Assuntos
Miopia , Esclera , Animais , Cobaias , Modelos Animais de Doenças , Esclera/patologia , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Miopia/tratamento farmacológico , Miopia/prevenção & controle , Miopia/patologia , Fibroblastos/patologia , Impressão Tridimensional
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(2): 249-255, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38385240

RESUMO

Objective: To review the research progress of new antibacterial hydrogels in the treatment of infected wounds in the field of biomedicine, in order to provide new methods and ideas for clinical treatment of infected wounds. Methods: The research literature on antibacterial hydrogels at home and abroad was extensively reviewed in recent years, and the antibacterial hydrogels for the treatment of infected wounds were classified and summarized. Results: Antibacterial hydrogels can be divided into three categories: inherent antibacterial hydrogels, antibacterial agent release hydrogels, and environmental response antibacterial hydrogels. The advantages and disadvantages of antibacterial materials, antibacterial mechanism, antibacterial ability, and biocompatibility were discussed respectively. Inherent antibacterial hydrogels have the characteristics of wide source, low cost, and simple preparation, but their antibacterial ability is relatively weak. New antimicrobial substances are added to antibacterial agent release hydrogels, such as antimicrobial peptides, metal ions, graphene materials, etc., providing a new therapeutic strategy for alternative antibiotic therapy. On the basis of the antibacterial material, environmental promoting factors such as photothermal effect, pH value, and magnetic force are added to the environmental response antibacterial hydrogels, which synergically enhances the antibacterial ability of the hydrogel, improves the precise regulation function and bionic effect of the hydrogel. Conclusion: The selection of a variety of materials, the addition of a variety of antibacterial agents, and the effect of various promoting factors make composite hydrogels show multiple characteristics. The development of antibacterial hydrogels that can effectively address practical clinical applications remains a significant challenge. In the future, expanding the application range of antibacterial hydrogels, constructing drug-loaded hydrogels, and developing intelligent hydrogels are still new areas that need to be explored and studied.


Assuntos
Grafite , Infecção dos Ferimentos , Humanos , Hidrogéis/uso terapêutico , Antibacterianos/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico
14.
Biomacromolecules ; 25(3): 1602-1611, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38323536

RESUMO

Helicobacter pylori can cause various gastric conditions including stomach cancer in an acidic environment. Although early H. pylori infections can be treated by antibiotics, prolonged antibiotic administrations may lead to the development of antimicrobial resistance, compromising the effectiveness of the treatments. Antimicrobial peptides (AMPs) have been reported to possess unique advantages against antimicrobial-resistant bacteria due to their rapid physical membrane disruptions and anti-inflammation/immunoregulation properties. Herein, we have developed an AMP hydrogel, which can be orally administered for the treatment of H. pylori infection. The hydrogel has potent antimicrobial activity against H. pylori, achieving bacterial eradication within minutes of action. Compared with the AMP solution, the hydrogel formulation significantly reduced the cytotoxicity and enhanced proteolytic stability. In vivo experiments suggested that the hydrogel formed at pH 4 had superior therapeutic effects to those at pH 7 and 10 hydrogels, attributed to its rapid release and bactericidal action within the acidic stomach environment. Compared to conventional antibiotic treatments, the AMP hydrogel had the advantages of fast bacterial killing in the gastric juice and obviated proton pump inhibitors during the treatment. Although both the AMP hydrogel and antibiotics suppressed the expression of pro-inflammatory cytokines, the former uniquely promoted inflammation resolution. These results indicate that the AMP hydrogels with effectiveness and biosafety may be potential candidates for the clinical treatment of H. pylori infections.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Peptídeos Antimicrobianos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Antibacterianos
15.
Colloids Surf B Biointerfaces ; 235: 113761, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281392

RESUMO

Diabetes is a widespread epidemic that includes a number of comorbid conditions that greatly increase the chance of acquiring other chronic illnesses. Every year, there are significantly more people with diabetes because of the rise in type-2 diabetes prevalence. The primary causes of illness and mortality worldwide are, among these, hyperglycemia and its comorbidities. There has been a lot of interest in the creation of peptide-based hydrogels as a potentially effective platform for the treatment of diabetes and its consequences. Here, we emphasize the use of self-assembled hydrogel formulations and their unique potential for the treatment/management of type-2 diabetes and its consequences. (i.e., wounds). Key aspects covered include the characteristics of self-assembled peptide hydrogels, methods for their preparation, and their pre-clinical and clinical applications in addressing metabolic disorders such as type-2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Humanos , Cicatrização , Hidrogéis/uso terapêutico , Peptídeos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico
16.
Acta Biomater ; 176: 173-189, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38244658

RESUMO

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. STATEMENT OF SIGNIFICANCE: Lumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.


Assuntos
Deslocamento do Disco Intervertebral , Ciática , Camundongos , Animais , Ciática/tratamento farmacológico , Ciática/etiologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/tratamento farmacológico , Ácido Hialurônico , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Doenças Neuroinflamatórias , Betametasona/farmacologia , Betametasona/uso terapêutico , Compostos de Sulfidrila
17.
Nat Commun ; 15(1): 864, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38286997

RESUMO

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.


Assuntos
Hidrogéis , Infarto do Miocárdio , Suínos , Ratos , Animais , Hidrogéis/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Porco Miniatura , Arritmias Cardíacas , Suturas , Remodelação Ventricular
18.
ACS Nano ; 18(4): 3087-3100, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38235966

RESUMO

Breast cancer is the most commonly diagnosed cancer, and surgical resection is the first choice for its treatment. With the development of operation techniques, surgical treatment for breast cancer is evolving toward minimally invasive and breast-conserving approaches. However, breast-conserving surgery is prone to an increased risk of cancer recurrence and is becoming a key challenge that needs to be solved. In this study, we introduce a one-shot injectable nano-in-gel vaccine (NIGel-Vax) for postoperative breast cancer therapy. The NIGel-Vax was constructed by mixing protein antigens with PEI-4BImi-Man adjuvant and then encapsulated in a hydrogel made with oxidized dextran (ODEX) and 4-arm PEG-ONH2. Using 4T1 tumor-extracted proteins as antigen, the NIGel-Vax achieved a 92% tumor suppression rate and a 33% cure rate as a postoperative therapy in the 4T1 tumor model. Using the tumor-associated antigen trophoblast cell-surface antigen 2 (TROP2) protein as the antigen, NIGel-Vax achieved a 96% tumor suppression rate and a 50% cure rate in triple-negative breast cancer (TNBC) models. This design provides an encouraging approach for breast cancer postoperative management.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Vacinas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Nanovacinas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Mastectomia Segmentar , Hidrogéis/uso terapêutico , Linhagem Celular Tumoral
19.
Artigo em Inglês | MEDLINE | ID: mdl-38072393

RESUMO

The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within the tumor microenvironment (TME) to regulate tumor metabolism, proliferation, and promote tumor metastasis as well as angiogenesis, consequently leading to treatment failure and recurrence. In recent years, widespread attempts have been made to overcome tumor hypoxia through different methods, such as hyperbaric oxygen therapy (HBOT), hyperthermia, O2 carriers, artificial hemoglobin, oxygen generator hydrogels, and peroxide materials. While oxygen is found to be an essential agent to improve the treatment response of photodynamic therapy (PDT) and other cancer treatment modalities, the development of hypoxia within the tumor is highly associated with PDT failure. Recently, the use of nanoparticles has been a hot topic for researchers and exploited to overcome hypoxia through Oxygen-generating hydrogels, O2 nanocarriers, and O2 -generating nanoparticles. This review aimed to discuss the role of nanotechnology in tumor oxygenation and highlight the challenges, prospective, and recent advances in this area to improve PDT outcomes. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Hipóxia Tumoral , Estudos Prospectivos , Nanotecnologia , Oxigênio/uso terapêutico , Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Hipóxia/tratamento farmacológico , Hidrogéis/uso terapêutico , Microambiente Tumoral , Linhagem Celular Tumoral
20.
Int Wound J ; 21(1): e14366, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37705319

RESUMO

Wound infections and delayed complications after caesarean section surgical procedure to mothers would have a prevalence of discomfort, stress and dissatisfaction in the postpartum period. In this report, one-pot synthesis is used for the preparation of chitosan (CS)-based copper nanoparticles (nCu), which was used for the preparation of zinc oxide (ZnO) hydrogel as wound dressing materials after surgery. The antibacterial activity of (CS-nCu/ZnO) developed hydrogels was studied zone of inhibition, against gram-positive and gram-negative bacteria. The antibacterial activity of the CS-nCu/ZnO hydrogel demonstrated that nanoformulated hydrogel materials have provided excellent bactericidal action against clinically approved bacterial pathogens. The biocompatibility and in vitro wound healing potential of the developed wound closure materials were studied by MTT assay and wound scratch assay methods, respectively. The MTT assay and cell migration assay results demonstrated that CS-nCu/ZnO hydrogel material induces cell compatibility and effective cell proliferation ability. These findings suggest that the CS-nCu/ZnO hydrogel outperforms CS-ZnO in terms of wound healing and could be used as a wound closure material in caesarean section wound treatment.


Assuntos
Quitosana , Óxido de Zinco , Gravidez , Humanos , Feminino , Óxido de Zinco/uso terapêutico , Óxido de Zinco/farmacologia , Quitosana/uso terapêutico , Antibacterianos/farmacologia , Cobre/uso terapêutico , Cobre/farmacologia , Hidrogéis/uso terapêutico , Cesárea , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Cicatrização , Bandagens
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