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1.
PLoS Negl Trop Dis ; 17(12): e0011776, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38039267

RESUMO

BACKGROUND: CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. METHODOLOGY/PRINCIPAL FINDINGS: We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. CONCLUSION/SIGNIFICANCE: The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate.


Assuntos
Esquistossomose mansoni , Esquistossomose , Esquistossomicidas , Camundongos , Animais , Coelhos , Esquistossomose mansoni/parasitologia , Schistosoma mansoni , Esquistossomose/tratamento farmacológico , Anticorpos Anti-Helmínticos , Esquistossomicidas/farmacologia , Polímeros/farmacologia , Polímeros/uso terapêutico , Antígenos de Helmintos
2.
Int J Biol Macromol ; 253(Pt 8): 127460, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37866559

RESUMO

Conventional cancer mono-therapeutic approaches including radiotherapy, surgery, and chemotherapy don't always achieve satisfactory outcomes and are frequently associated with significant limitations. Although chemotherapy is a vital intervention, its effectiveness is frequently inadequate and is associated with metastasis, multidrug resistance, off-target effect, and normal cells toxicity. Phototherapies are employed in cancer therapy, encompassing photo-dynamic and photo-thermal therapies which under favorable NIR laser light irradiation initiate the included photosensitizers and photo-thermal agents to generate ROS or thermal heat respectively for cancer cells destruction. Photo-therapy is considered noninvasive, posing no resistance, but it still suffers from several pitfalls like low penetration depth and excessive heat generation affecting neighboring tissues. Improved selectivity and tumor-homing capacity could be attained through surface modulation of nanoparticles with targeting ligands that bind to receptors, which are exclusively overexpressed on cancerous cells. Developing novel modified targeted nanoparticulate platforms integrating different therapeutic modalities like photo-therapy and chemotherapy is a topic of active research. This review aimed to highlight recent advances in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers for smart combinatorial chemotherapy/photo-therapy. Nanocarriers decorated with precise targeting ligands, like aptamers, antibody, and lactoferrin, to achieve active tumor-targeting or camouflaging using various biological cell membrane coating are designed to achieve homologous tumor-targeting.


Assuntos
Nanopartículas , Neoplasias , Ácidos Nucleicos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Sistemas de Liberação de Medicamentos , Fármacos Fotossensibilizantes/farmacologia , Membrana Celular
3.
Saudi J Biol Sci ; 30(6): 103661, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37163156

RESUMO

COVID-19 has spread to over 200 countries with variable severity and mortality rates. Computational analysis is a valuable tool for developing B-cell and T-cell epitope-based vaccines. In this study, by harnessing immunoinformatics tools, we designed a multiple-epitope vaccine to protect against COVID-19. The candidate epitopes were designed from highly conserved regions of the SARS-CoV-2 spike (S) glycoprotein. The consensus amino acids sequence of ten SARS-CoV-2 variants including Gamma, Beta, Epsilon, Delta, Alpha, Kappa, Iota, Lambda, Mu, and Omicron was involved. Applying the multiple sequence alignment plugin and the antigenic prediction tools of Geneious prime 2021, ten predicted variants were identified and consensus S-protein sequences were used to predict the antigenic part. According to ElliPro analysis of S-protein B-cell prediction, we explored 22 continuous linear epitopes with high scores ranging from 0.879 to 0.522. First, we reported five promising epitopes: BE1 1115-1192, BE2 481-563, BE3 287-313, BE4 62-75, and BE5 112-131 with antigenicity scores of 0.879, 0.86, 0.813, 0.779, and 0.765, respectively, while only nine discontinuous epitopes scored between 0.971 and 0.511. Next, we identified 194 Major Histocompatibility Complex (MHC) - I and 156 MHC - II epitopes with antigenic characteristics. These spike-specific peptide-epitopes with characteristically high immunogenic and antigenic scores have the potential as a SARS-CoV-2 multiple-epitope peptide-based vaccination strategy. Nevertheless, further experimental investigations are needed to test for the vaccine efficacy and efficiency.

4.
Pharmaceutics ; 15(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37242760

RESUMO

Wound healing has grown to be a significant problem at a global scale. The lack of multifunctionality in most wound dressing-based biopolymers prevents them from meeting all clinical requirements. Therefore, a multifunctional biopolymer-based tri-layered hierarchically nanofibrous scaffold in wound dressing can contribute to skin regeneration. In this study, a multifunctional antibacterial biopolymer-based tri-layered hierarchically nanofibrous scaffold comprising three layers was constructed. The bottom and the top layers contain hydrophilic silk fibroin (SF) and fish skin collagen (COL), respectively, for accelerated healing, interspersed with a middle layer of hydrophobic poly-3-hydroxybutyrate (PHB) containing amoxicillin (AMX) as an antibacterial drug. The advantageous physicochemical properties of the nanofibrous scaffold were estimated by SEM, FTIR, fluid uptake, contact angle, porosity, and mechanical properties. Moreover, the in vitro cytotoxicity and cell healing were assessed by MTT assay and the cell scratching method, respectively, and revealed excellent biocompatibility. The nanofibrous scaffold exhibited significant antimicrobial activity against multiple pathogenic bacteria. Furthermore, the in vivo wound healing and histological studies demonstrated complete wound healing in wounded rats on day 14, along with an increase in the expression level of the transforming growth factor-ß1 (TGF-ß1) and a decrease in the expression level of interleukin-6 (IL-6). The results revealed that the fabricated nanofibrous scaffold is a potent wound dressing scaffold, and significantly accelerates full-thickness wound healing in a rat model.

5.
Int J Biol Macromol ; 239: 124294, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37004933

RESUMO

Phototherapies or light mediated therapies, including mutually photothermal and photodynamic therapy that encompass irradiation of the target organs with light, have been widely employed as minimally invasive approach associated with negligible drug resistance for eradicating multiple tumors with minimal hazards to normal organs. Despite all these advantages, many obstacles in phototherapy hinder progress toward clinical application. Therefore, researchers have developed nano-particulate delivery systems integrated with phototherapy and therapeutic cytotoxic drugs to overcome these obstacles and achieve maximum efficacy in cancer treatment. Active targeting ligands were integrated into their surfaces to improve the selectivity and tumor targeting ability, enabling easy binding and recognition by cellular receptors overexpressed on the tumor tissue compared to normal ones. This enhances intratumoral accumulation with minimal toxicity on the adjacent normal cells. Various active targeting ligands, including antibodies, aptamers, peptides, lactoferrin, folic acid and carbohydrates, have been explored for the targeted delivery of chemotherapy/phototherapy-based nanomedicine. Among these ligands, carbohydrates have been applied due to their unique features that ameliorate the bioadhesive, noncovalent conjugation to biological tissues. In this review, the up-to-date techniques of employing carbohydrates active targeting ligands will be highlighted concerning the surface modification of the nanoparticles for ameliorating the targeting ability of the chemo/phototherapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Nanomedicina , Sistemas de Liberação de Medicamentos/métodos , Fototerapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
6.
J Genet Eng Biotechnol ; 20(1): 133, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094767

RESUMO

BACKGROUND: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) is one of the most critical pathogens in wound infections, causing high mortality and morbidity in severe cases. However, bacteriophage therapy is a potential alternative to antibiotics against P. aeruginosa. Therefore, this study aimed to isolate a novel phage targeting P. aeruginosa and examine its efficacy in vitro and in vivo. RESULTS: The morphometric and genomic analyses revealed that ZCPA1 belongs to the Siphoviridae family and could infect 58% of the tested antibiotic-resistant P. aeruginosa clinical isolates. The phage ZCPA1 exhibited thermal stability at 37 °C, and then, it decreased gradually at 50 °C and 60 °C. At the same time, it dropped significantly at 70 °C, and the phage was undetectable at 80 °C. Moreover, the phage ZCPA1 exhibited no significant titer reduction at a wide range of pH values (4-10) with maximum activity at pH 7. In addition, it was stable for 45 min under UV light with one log reduction after 1 h. Also, it displayed significant lytic activity and biofilm elimination against P. aeruginosa by inhibiting bacterial growth in vitro in a dose-dependent pattern with a complete reduction of the bacterial growth at a multiplicity of infection (MOI) of 100. In addition, P. aeruginosa-infected wounds treated with phages displayed 100% wound closure with a high quality of regenerated skin compared to the untreated and gentamicin-treated groups due to the complete elimination of bacterial infection. CONCLUSION: The phage ZCPA1 exhibited high lytic activity against MDR P. aeruginosa planktonic and biofilms. In addition, phage ZCPA1 showed complete wound healing in the rat model. Hence, this research demonstrates the potential of phage therapy as a promising alternative in treating MDR P. aeruginosa.

7.
Polymers (Basel) ; 14(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35160444

RESUMO

The process of secondary intention wound healing includes long repair and healing time. Electrospun nanofibrous scaffolds have shown potential for wound dressing. Biopolymers have gained much attention due to their remarkable characteristics such as biodegradability, biocompatibility, non-immunogenicity and nontoxicity. This study anticipated to develop a new composite metronidazole (MTZ) immobilized nanofibrous scaffold based on poly (3-hydroxy butyrate) (PHB) and Gelatin (Gel) to be utilized as a novel secondary intention wound healing accelerator. Herein, PHB and Gel were mixed together at different weight ratios to prepare polymer solutions with final concentration of (7%), loaded with two different concentrations 5% (Z1) and 10% (Z2) of MTZ. Nanofibrous scaffolds were obtained by manipulating electrospinning technique. The properties of MTZ immobilized PHB/Gel nanofibrous scaffold were evaluated (SEM, FTIR, TGA, water uptake, contact angle, porosity, mechanical properties and antibacterial activity). Additionally, in vitro cytocompatibility of the obtained nanofibrous scaffolds were assessed by using the cell counting kit-8 (CCK-8 assay). Moreover, in vivo wound healing experiments revealed that the prepared nanofibrous scaffold highly augmented the transforming growth factor (TGF-ß) signaling pathway, moderately suppressed the pro-inflammatory cytokine (IL-6). These results indicate that MTZ immobilized PHB/Gel nanofibrous scaffold significantly boost accelerating secondary intention wound healing.

8.
Int J Biol Macromol ; 197: 121-130, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34963623

RESUMO

In this present work, a new design for antimicrobial wound bandages is presented. The wound dressings were prepared using cotton fibers reinforced with elastic compression straps and secured with a polyester fabric of tight mesh size. The cotton pads were doped with a wound healing biocomposite, composed of chitosan, glycogen, and ZnO nanoparticles (CG@ZnONPs) previously formulated through a green process. The size of ZnONPs in the prepared CG@ZnONPs was 30-80 nm. The cotton pads impregnated with the CG@ZnONPs nanocomposite were characterized using FTIR, SEM, EDX, TGA, and DTGA methods. Moreover, the prepared dressings were tested on a number of intentionally injured rats. In this experiment, the % contraction of the treated wounds was monitored and compared to that of a control group of wounded rats, to which only sterile gauzes were applied. The results showed a much faster and an almost complete healing of rats treated with the synthesized dressings and the results were further confirmed by histopathological examination. The dressings were also found to exert a significant antimicrobial activity against a number of pathogenic microorganisms, generally encountered in common wounds, and could therefore be recommended to be a novel biomedical application for a fast, successful, and flawless wounds healing process.


Assuntos
Quitosana
9.
Artigo em Inglês | MEDLINE | ID: mdl-34837816

RESUMO

A rapid, efficient, and sensitive liquid chromatographic assay hyphenated to fluorometric detector (HPLC-FLD) was developed and validated for the determination of doxorubicin (DXR) and prodigiosin (PDG) in rat plasma. The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency (98% and 85% for DXR and PDG, respectively). The chromatographic separation was accomplished using stationary phase: Agilent Zorbax Eclipse plus-C18 analytical column (250 × 4.6 mm, 5 µm) and gradient eluting mobile phase of ammonium acetate (pH = 3), acetonitrile and methanol with programmed fluorescence detection. As the proposed method has been validated, it was subsequently implemented to evaluate DXR and PDG loaded on novel eco-friendly Casein nano drug delivery system after intravenous injection in healthy rats. A comparative pharmacokinetics' study was carried out in rats for DXR in free form, DXR alone entrapped in the nanomicelle and DXR with PDG entrapped in the nano micelle. After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters. This indicates that the presented nanomicelle delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe, and potent formulation. This novel nanomicelle has negligible effect on the distribution and elimination of DXR.


Assuntos
Caseínas/química , Doxorrubicina/sangue , Micelas , Sistemas de Liberação de Fármacos por Nanopartículas/química , Prodigiosina/sangue , Animais , Caseínas/sangue , Caseínas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Doxorrubicina/química , Doxorrubicina/farmacocinética , Masculino , Sistemas de Liberação de Fármacos por Nanopartículas/análise , Sistemas de Liberação de Fármacos por Nanopartículas/farmacocinética , Prodigiosina/química , Prodigiosina/farmacocinética , Ratos , Ratos Wistar , Espectrometria de Fluorescência
10.
Antibiotics (Basel) ; 10(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34572629

RESUMO

(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP.

11.
Polymers (Basel) ; 13(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34372035

RESUMO

Much attention has been paid to chitosan biopolymer for advanced wound dressing owing to its exceptional biological characteristics comprising biodegradability, biocompatibility and respectable antibacterial activity. This study intended to develop a new antibacterial membrane based on quaternized aminochitosan (QAMCS) derivative. Herein, aminochitosan (AMCS) derivative was quaternized by N-(2-Chloroethyl) dimethylamine hydrochloride with different ratios. The pre-fabricated membranes were characterized by several analysis tools. The results indicate that maximum surface potential of +42.2 mV was attained by QAMCS3 membrane compared with +33.6 mV for native AMCS membrane. Moreover, membranes displayed higher surface roughness (1.27 ± 0.24 µm) and higher water uptake value (237 ± 8%) for QAMCS3 compared with 0.81 ± 0.08 µm and 165 ± 6% for neat AMCS membranes. Furthermore, the antibacterial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus cereus. Superior antibacterial activities with maximum inhibition values of 80-98% were accomplished by QAMCS3 membranes compared with 57-72% for AMCS membrane. Minimum inhibition concentration (MIC) results denote that the antibacterial activities were significantly boosted with increasing of polymeric sample concentration from 25 to 250 µg/mL. Additionally, all membranes unveiled better biocompatibility and respectable biodegradability, suggesting their possible application for advanced wound dressing.

12.
Int J Pharm ; 607: 120965, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34339814

RESUMO

Targeted delivery of cytotoxic drugs has shown great potential in cancer therapy. In this light, vitamin D3 (vit.D3)-coated micelles were fabricated to encapsulate the cytotoxic drug; etoposide (ETP). Sodium caseinate micelles were first utilized to encapsulate vit.D3 and ETP within their hydrophobic core, then drug-loaded micelles were further decorated with an envelope of vit.D3/ phospholipid complex to enhance the active targeting potency of fabricated micelles via exploiting vit.D3 receptors (VDRs) overexpressed on the outer surface of breast cancer cells. In vitro cytotoxicity studies showed that fabricated micelles exhibited improved anticancer effect on MDA MB-231 and MCF-7 human breast cancer cell lines in comparison to free vit.D3 + ETP without any significant toxicity on normal human lung fibroblast (Wi-38) cells. In vivo biodistribution and efficacy studies in Ehrlich ascites tumor animal model revealed that fabricated micelles manifested improved accumulation in tumor tissue due to active targeting potential of vit.D3 without any remarkable toxicity. More importantly, fabricated micelles resulted in enhanced tumor apoptosis, reduced angiogenesis, invasion and autophagy, besides a decline in the tumor expression levels of both miR-21 and miR-192. Therefore, vit.D3/ETP micelles could serve as a favorable actively targeted anticancer delivery system having a superior effect over the free combination.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Caseínas , Linhagem Celular Tumoral , Colecalciferol , Feminino , Humanos , Micelas , Fosfolipídeos , Distribuição Tecidual
13.
Int J Biol Macromol ; 167: 1527-1543, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33212102

RESUMO

A successful drug delivery to a specific site relies on two essential factors including; efficient entrapment of the drug within the carrier and successful delivery of drug- loaded nanocarrier to the target site without opsonisation or drug release in the circulation before reaching the organ of interest. Lactoferrin (LF) is a glycoprotein belonging to the transferrin (TF) family which can bind to TF receptors (TFRs) and LF membrane internalization receptors (LFRs) highly expressed on the cell surface of both highly proliferating cancer cells and blood brain barrier (BBB), which in turn can facilitate its accessibility to the cell nucleus. This merit could be exploited to develop actively targeted drug delivery systems that can easily cross the BBB or internalize into tumor cells. In this review, the most recent advances of utilizing LF as an active targeting ligand for different types of nanocarriers including: inorganic nanoparticles, dendrimers, synthetic biodegradable polymers, lipid nanocarriers, natural polymers, and nanoemulstions will be highlighted. Collectively, LF seems to be a promising targeting ligand in the field of nanomedicine.


Assuntos
Portadores de Fármacos/metabolismo , Lactoferrina/metabolismo , Lipossomos/metabolismo , Nanomedicina/métodos , Nanopartículas/química , Neoplasias/metabolismo , Receptores da Transferrina/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Dendrímeros/química , Liberação Controlada de Fármacos , Humanos , Lactoferrina/química , Lipossomos/química , Nanopartículas de Magnetita/química , Nanopartículas/metabolismo , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Transferrina/metabolismo
14.
Int J Biol Macromol ; 167: 1552-1563, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33212109

RESUMO

An innovative approach in the functionalization of nanofibers (NFs) for wound healing relies on non-antibiotic combinational therapy to subdue microbial invasion while reducing antimicrobial resistance and enhancing healing. Despite great potentials, wound healing efficacy of NFs embedding antimicrobial metal nanoparticles (NPs)/essential oils has been scarcely documented. We developed combinational NFs using an electrospinnable hyaluronic acid/polyvinyl alcohol/polyethylene oxide blend embedding a new ZnO NPs/cinnamon essential oil (CEO) antimicrobial combination. Fourier transform infrared, X-ray diffraction and transmission electron microscopy confirmed the presence of HA and distribution of ZnO NPs and CEO within NFs. Results for mean diameter, thermal stability, hydrophilicity, tensile strength, in vitro biodegradability, and cytocompatibility of crosslinked combinational NFs were intermediate between those of their singly loaded counterparts. All NFs inhibited the growth of Staphylococcus aureus (S. aureus). Compared with singly loaded NFs, combinational NFs showed the greatest healing efficacy of full thickness S. aureus inoculated incision wounds in rats in terms of bacterial inhibition following a single application, healing speed, and quality of skin structure recovery as verified by morphological, microbiological, and histopathological studies. Results highlighted the potentials of metal NPs/essential oil functionalization of nanofibrous wound dressings as an emerging antibiotic-free combinational approach for more effective and safer wound healing.


Assuntos
Anti-Infecciosos/farmacologia , Ácido Hialurônico/farmacologia , Nanofibras/química , Óleos Voláteis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Cinnamomum zeylanicum/química , Reagentes de Ligações Cruzadas/química , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Masculino , Teste de Materiais , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanofibras/toxicidade , Nanofibras/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Álcool de Polivinil/química , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Resistência à Tração , Difração de Raios X , Óxido de Zinco/química
15.
Sci Rep ; 10(1): 14706, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895397

RESUMO

Prodigiosin, a secondary metabolite red pigment produced by Serratia marcescens, has an interesting apoptotic efficacy against cancer cell lines with low or no toxicity on normal cells. HSP90α is known as a crucial and multimodal target in the treatment of TNBC. Our research attempts to assess the therapeutic potential of prodigiosin/PU-H71 combination on MDA-MB-231 cell line. The transcription and protein expression levels of different signalling pathways were assessed. Treatment of TNBC cells with both drugs resulted in a decrease of the number of adherent cells with apoptotic effects. Prodigiosin/PU-H71 combination increased the levels of caspases 3,8 and 9 and decreased the levels of mTOR expression. Additionally, there was a remarkable decrease of HSP90α transcription and expression levels upon treatment with combined therapy. Also, EGFR and VEGF expression levels decreased. This is the first study to show that prodigiosin/PU-H71 combination had potent cytotoxicity on MDA-MB-231 cells; proving to play a paramount role in interfering with key signalling pathways in TNBC. Interestingly, prodigiosin might be a potential anticancer agent to increase the sensitivity of TNBC cells to apoptosis. This study provides a new basis for upcoming studies to overcome drug resistance in TNBC cells.


Assuntos
Benzodioxóis/farmacologia , Prodigiosina/farmacologia , Purinas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Receptores ErbB/metabolismo , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Int J Biol Macromol ; 164: 1046-1060, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707283

RESUMO

Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine.


Assuntos
Portadores de Fármacos/química , Lactoferrina/química , Nanotecnologia/métodos , Animais , Anti-Inflamatórios/química , Antineoplásicos/farmacologia , Antioxidantes/química , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Suplementos Nutricionais , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Humanos , Camundongos , Micelas , Nanopartículas/química , Tamanho da Partícula
17.
Int J Biol Macromol ; 162: 246-261, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531361

RESUMO

Alzheimer's disease (AD) is neurological disorder characterized by dementia which causes severe problems with behavior, thinking and memory. Systemic administration of therapeutics to the central nervous system (CNS) is usually associated with very low efficiency due to presence of blood brain barrier (BBB), which only allows permeation of few types of molecules from the circulation to the CNS. As an alternative, naturally amphiphilic micelles can be utilized to enhance targeted drug delivery to the brain. In this sense, lactoferrin (LF) was covalently attached to conjugated linoleic acid (CLA) via carbodiimide coupling reaction to form a new micellar nanoplatform with particle size of about 53 nm. Afterwards, fabricated micelles were further loaded once again with CLA to enhance its delivery to the CNS. In vitro drug release study revealed that CLA exhibited sustained release at pH 6.8, associated with good hemocompatibility without any remarkable in vivo toxicity in terms of liver and kidney functions. Moreover, in vivo studies showed that the fabricated micelles manifested enhanced in vivo biodistrbution in brain tissue due to the active targeting potential of LF. Additionally, drug-loaded LF-CLA micelles exhibited enhanced cognitive capabilities, reduced brain oxidative stress, inflammation, apoptosis and acetylcholine esterase activity, besides a decline in the deposition of amyloid ß peptide1-42 in aluminum chloride Alzheimer's-induced animal model. CLA-based micelles could be a promising CNS actively targeted delivery system with a sophisticated potential to reduce AD symptoms.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Portadores de Fármacos/química , Lactoferrina/administração & dosagem , Ácidos Linoleicos Conjugados/administração & dosagem , Memória/efeitos dos fármacos , Nanoestruturas/química , Acetilcolinesterase/metabolismo , Administração Oral , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/efeitos dos fármacos , Escala de Avaliação Comportamental , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Lactoferrina/farmacologia , Lactoferrina/toxicidade , Ácidos Linoleicos Conjugados/farmacologia , Ácidos Linoleicos Conjugados/toxicidade , Fígado/efeitos dos fármacos , Masculino , Micelas , Microscopia Eletrônica de Transmissão , Nanoestruturas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Carbohydr Polym ; 238: 116175, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32299548

RESUMO

The current study is pertaining to develop a novel wound dressing, comprising natural biologically absorbable materials for wound healing In-vivo. Wound dressing is composed of Polygalacturonic acid, Hyaluronic acid embedded silver nanoparticles, which is further fabricated to form nanofibrous mat, using electrospinning. Silver nanoparticles was prepared using PGA. AgNPs in this formula will serve as an antioxidant and anti-inflammatory that protect cells from destructive effect of elevated ROS and accelerate wound healing. The physical performance and water contact angle for nanofiber was evaluated. The produced nanofiber was characterized by Fourier-transform infrared (FTIR), scanning electron microscopy and thermal analysis. Also, the embedded AgNPs was also characterized by UV-vis spectroscopy and TEM. The nanofiber mates embedded AgNPs was applied to the wounded site of albino rats in-vivo. Histopathological assessment for the wound was fully performed. Also, the antimicrobial activity for the fabricated wound dressing was evaluated against gram+ve and gram -ve bacteria.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bandagens , Nanopartículas Metálicas/uso terapêutico , Nanofibras/uso terapêutico , Prata/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Ácido Hialurônico/química , Masculino , Pectinas/química , Ratos , Prata/química
19.
Eur J Pharm Sci ; 144: 105224, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954183

RESUMO

Nanofibers provide multiple merits for the delivery of many therapeutic agents with versatile biomedical applications. With the fast recent advancement in nanotechnology, nanofibers could be easily fabricated with tunable morphologies and release profiles. Here, we review the most recent approaches in the fabrication of electrospun nanofibers incorporating some natural ingredients for their wound healing potential. In addition, electrospun nanofibers for treatment of skin carcinoma and delivery of different growth factors for tissue regeneration will also be highlighted in this review. Nanofibers incorporating different active therapeutical agents are very promising drug delivery platforms.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanofibras , Animais , Anti-Infecciosos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Nanotecnologia , Neoplasias Cutâneas , Cicatrização
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