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1.
Nanoscale ; 13(31): 13328-13343, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477739

RESUMO

Facing the barriers in each step of the in vivo delivery cascade, the low drug delivery efficiency remains problematic in tumor therapy. Although recently the nanofibril drug delivery systems have shown improved circulation and accumulation compared with nanoparticles, the poor deep penetration and cellular internalization hinder their application, especially for pancreatic cancer with dense stroma. To comprehensively address the hurdles in the delivery cascade, a matrix metalloproteinase 2 (MMP-2) responsive transformable beaded nanofibril, which integrates the merits of nanofibril and small-sized nanoparticles, is established. The beaded nanofibril (GD@PPF) is prepared by conjugating gemcitabine-loaded small-sized nanoparticles (GD) with fibrous PEG-PCL (PPF) via GPLGVRG, a substrate peptide of MMP-2. GD@PPF escapes the clearance of the reticuloendothelial system (RES), prolongs the circulation time, and increases the selective accumulation in the tumor as fibrous micelles. Once accumulated in the tumor, small positively-charged GD is released from the beaded nanofibrils in response to MMP-2 overexpression in the stroma of pancreatic cancer, enabling permeation in the dense tumor matrix and cellular internalization, which makes up for the shortcomings of fibrous micelles. Furthermore, the remaining fibrous PPF surround the tumor tightly to impede the efflux of drugs, leading to improved retention. GD@PPF is biocompatible and exhibits excellent antitumor effect in Pan 02 subcutaneous tumor models. Therefore, the MMP-2 responsive transformable beaded nanofibril, which enhances the delivery efficiency in multiple stage of the delivery cascade, presents a promising strategy for pancreatic cancer therapy.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Metaloproteinase 2 da Matriz , Micelas , Neoplasias Pancreáticas/tratamento farmacológico
2.
Curr Protoc ; 1(9): e230, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491629

RESUMO

Progress in extracellular vesicle (EV) research over the past two decades has generated significant interest in using EVs in the biomedical field. Exosomes are a subgroup of EVs that comprise endocytic membrane-bound nanovesicles of 40 to 160 nm diameter. These vesicles have been shown to facilitate intercellular communication via the delivery of cellular molecules. There are currently several exciting applications for exosomes being developed in therapeutics, diagnostics, drug delivery, and cellular reprogramming. Stem cell-derived exosomes present the opportunity to harness the power of stem cells while circumventing several of the risks associated with their use. This review summarizes the recent developments in exosome technology and lends a prospective view to the future of exosome use and application in research and medicine. Through a review of relevant patent filings, recent literature, and ongoing clinical trials, a valuable overview of the field of exosomes is provided. © 2021 Wiley Periodicals LLC.


Assuntos
Exossomos , Vesículas Extracelulares , Sistemas de Liberação de Medicamentos , Estudos Prospectivos , Células-Tronco
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112275, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474834

RESUMO

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria. However, these treatments are not efficient against severe malaria and improvements are needed. Primaquine (PQ) is one of the most widely used antimalarial drugs. It is the only available drug to date for combating the relapsing form of malaria. Nevertheless, it has severe side effects. Particle drug-delivery systems present the ability to enhance the therapeutic properties of drugs and decrease their side effects. Here, we report the development of Polymeric Primaquine Microparticles (PPM) labeled with 99mTc for therapeutic strategy against malaria infection. The amount of primaquine encapsulated into the PPM was 79.54%. PPM presented a mean size of 929.47 ± 37.72 nm, with a PDI of 0.228 ± 0.05 showing a homogeneous size for the microparticles and a monodispersive behavior. Furthermore, the biodistribution test showed that primaquine microparticles have a high liver accumulation. In vivo experiments using mice show that the PPM treatments resulted in partial efficacy and protection against the development of the parasite compared to free Primaquine. These results suggest that microparticles drug delivery systems of primaquine could be a possible approach for malaria prevention and treatment.


Assuntos
Malária , Preparações Farmacêuticas , Animais , Sistemas de Liberação de Medicamentos , Feminino , Fígado , Malária/tratamento farmacológico , Camundongos , Plasmodium falciparum , Primaquina/farmacologia , Primaquina/uso terapêutico , Distribuição Tecidual
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112302, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474853

RESUMO

Localized delivery of chemotherapeutic agents allows extended drug exposure at the target site, thereby reducing systemic toxicity. We report the development of functionalized polymeric patch with unidirectional drug release to treat gastric cancer. The oxaliplatin-loaded patch was prepared by incorporating sodium carboxymethyl cellulose, hydroxypropyl cellulose and polyvinylpyrrolidone. The patch was functionalized by coating with transferrin-poly(lactic-co-glycolic acid) conjugate on one side of the patch for cancer targeting. The other side of the patch was coated with ethylcellulose (EC) to restrict the release of oxaliplatin. The physical and mechanical properties of oxaliplatin-loaded patches were characterized. Mucoadhesion studies using excised rat stomach tissue have shown that the functionalized side of the patch has significantly (p < 0.05) greater mucoadhesion strength compared with EC coated side of the patch. The in vitro and ex vivo (stomach sac and open-membrane model) studies revealed greater permeation of oxaliplatin across the stomach tissue when adhered to the functionalized and non-functionalized side of the patch compared with EC coated side. It was found that the growth inhibition with oxaliplatin solution was not significantly greater compared with corresponding concentrations of oxaliplatin-loaded patch in AGS and Caco-2 cell models. The in vivo studies were performed in mice, where indocyanine green-loaded patch encapsulated in a gelatin capsule was orally administered. The near-infrared (NIR) optical imaging revealed adherence of the patch on the mucosal side of the stomach tissue for up to 6 h. In conclusion, the functionalized polymeric patch loaded with oxaliplatin can be a potential localized delivery system to target gastric cancer.


Assuntos
Neoplasias Gástricas , Animais , Células CACO-2 , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Oxaliplatina , Polímeros , Ratos , Neoplasias Gástricas/tratamento farmacológico
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112317, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474868

RESUMO

Acid-triggered degradable polyprodrug P(DOX-AH) was designed for long-acting drug delivery with minimal leakage and enhanced antitumor efficacy. By facile polymerization of doxorubicin (DOX) and N-(tert-butoxycarbonyl)acryloylhydrazine (Boc-AH), P(DOX-AH) with drug as unique repeating unit was obtained, possessing an ultrahigh drug content. It was stable in the neutral media but could degrade completely into DOX-AH in the acidic media without any other by-product. The cleavage of the hydrazone linkage between the DOX-AH repeating units was revealed by the LC-MS/MS analysis. Furthermore, a slow solubility-controlled drug release performance was achieved in the acidic media because of the low solubility of the released DOX-AH. Even with the slow DOX-AH releasing, the enhanced antitumor efficacy was obtained than free DOX in the in vitro cellular experiments. These features demonstrated the promising potential of the proposed polyprodrug for long-acting drug delivery in future tumor chemotherapy.


Assuntos
Polímeros , Espectrometria de Massas em Tandem , Cromatografia Líquida , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Micelas
6.
Mater Sci Eng C Mater Biol Appl ; 128: 112324, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474875

RESUMO

Pulmonary drug delivery is governed by several biophysical parameters of delivery carriers, such as particle size, shape, density, charge, and surface modifications. Although much attention has been given to other parameters, particle shape effects have rarely been explored. In this work, we assess the influence of particle shape of inhaled delivery carriers on their aerodynamic properties and macrophage uptake by using polymeric microparticles of different geometries ranging in various sizes. Doxorubicin was conjugated to the polymer particles and the bioconjugates were characterized. Interestingly, the results of in-vitro lung deposition, performed using a next generation impactor, demonstrated a significant improvement in the aerodynamic properties of the rod-shaped particles with a high aspect ratio as compared to spherical particles with the same equivalent volume. The results of a macrophage uptake experiment demonstrate that the high aspect ratio particles were phagocytosed less than spherical particles. Furthermore, the cytotoxicity of these doxorubicin-conjugated particles was determined against murine macrophages, resulting in reduced toxicity when treated with high aspect ratio particles as compared to spherical particles. This project provides valuable insights into the influence of particle shape on aerodynamic properties and primary defense mechanisms in the peripheral lungs, while using polymeric microparticles of various sizes and geometries. Further systematic development can help translate these findings to preclinical and clinical studies for designing efficient inhalable delivery carriers.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Administração por Inalação , Animais , Portadores de Fármacos , Pulmão , Camundongos , Tamanho da Partícula
7.
Mater Sci Eng C Mater Biol Appl ; 128: 112330, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474881

RESUMO

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumours. Despite advances in treatment modalities, it remains largely incurable with an extremely poor prognosis. Treatment of GBM is associated with several difficulties such as the risk of damaging healthy brain tissues during surgery, drug resistance and inadequate drug delivery across the blood brain barrier. The new nanomaterial graphene, has recently attracted great attention due to its unique physico-chemical characteristics, good biocompatibility, specific targeting and small size. Starting from simple drug delivery systems, the application of graphene-based nanomaterials has been extended to a versatile platform of multiple therapeutic modalities, including immunotherapy, gene therapy, photothermal therapy and photodynamic therapy. Graphene-based materials can also be engineered to integrate multiple functions into a single platform for combination therapy for enhanced anticancer activity and reduced side effects. This review aims to discuss the state-of-the-art applications of graphene-based materials in GBM diagnosis and therapy. In addition, future challenges and prospects regarding this promising field are discussed, which may pave the way towards improving the safety and efficacy of graphene-based therapeutics.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Grafite , Nanoestruturas , Fotoquimioterapia , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Grafite/uso terapêutico , Humanos
8.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3165-3170, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467709

RESUMO

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.


Assuntos
Aptâmeros de Nucleotídeos , Ácidos Nucleicos , Sistemas de Liberação de Medicamentos , Medicina Tradicional Chinesa , RNA Interferente Pequeno
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1192-1199, 2021 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-34523288

RESUMO

Objective: The properties and characteristics of different types of silk fibroin (SF) drug-loaded sustained-release carriers and their effects on the drug release behavior were reviewed, and the existing problems and development prospects of SF drug-loaded sustained-release carriers in tissue engineering drug delivery system were discussed. Methods: The literatures about drug-loaded SF sustained-release carriers in recent years were extensively consulted, and the types of sustained-release carriers, characteristics of drug release, range of applications, advantages and disadvantages, and solutions were summarized and analyzed. Results: At present, the SF drug-loaded sustained-release carriers are mainly divided into SF microparticles, SF scaffolds, SF membranes, SF hydrogels, SF nanofibers, SF sponges, and so on. These types of SF drug-loaded sustained-release carriers have their own advantages and problems, of which the most prominent problem is the burst release of drugs at the initial stage. While, the initial burst release of drugs can be effectively solved by improving the preparation process and adjusting the material ratio. Different types of drug-loaded sustained-release carriers can be prepared by combining different materials to achieve different application scopes and drug release behaviors under different conditions. Conclusion: SF is a good drug-loaded carrier for tissue engineering, the burst release of drugs at the initial stage can be solved by improving the preparation process and changing the material structure; through the combination of the advantages of various types of SF drug-loaded sustained-release carriers, it is expected to prepare SF drug-loaded sustained-release carriers that meet different clinical needs.


Assuntos
Fibroínas , Nanofibras , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Seda , Engenharia Tecidual
10.
Langmuir ; 37(33): 10200-10213, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34379976

RESUMO

Self-emulsifying drug-delivery systems (SEDDS) have been extensively shown to increase oral absorption of solvation-limited compounds. However, there has been little clinical and commercial use of these formulations, in large part because the demonstrated advantages of SEDDS have been outweighed by our inability to precisely predict drug absorption from SEDDS using current in vitro assays. To overcome this limitation and increase the biological relevancy of in vitro assays, an absorption function can be incorporated using biomimetic membranes. However, the effects that SEDDS have on the integrity of a biomimetic membrane are not known. In this study, a quartz crystal microbalance with dissipation monitoring and total internal reflection fluorescence microscopy were employed as complementary methods to in vitro lipolysis-permeation assays to characterize the interaction of various actively digested SEDDS with a liquescent artificial membrane comprising lecithin in dodecane (LiDo). Observations from surface analysis showed that interactions between the digesting SEDDS and LiDo membrane coincided with inflection points in the digestion profiles. Importantly, no indications of membrane damage could be observed, which was supported by flux profiles of the lipophilic model drug felodipine (FEL) and impermeable marker Lucifer yellow on the basal side of the membrane. There was a correlation between the digestion kinetics of the SEDDS and the flux of FEL, but no clear correlation between solubilization and absorption profiles. Membrane interactions were dependent on the composition of lipids within each SEDDS, with the more digestible lipids leading to more pronounced interactions, but in all cases, the integrity of the membrane was maintained. These insights demonstrate that LiDo membranes are compatible with in vitro lipolysis assays for improving predictions of drug absorption from lipid-based formulations.


Assuntos
Biomimética , Sistemas de Liberação de Medicamentos , Administração Oral , Emulsões , Intestino Delgado , Lecitinas , Solubilidade
11.
Eur J Pharm Sci ; 166: 105960, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339828

RESUMO

Our study aimed to formulate a novel dexamethasone (DXM)-loaded, mixed polymeric micelle-based drug delivery system, focusing on the auspicious nose-to-brain pathway, as a key delivery route to treat central nervous system (CNS) associated diseases. Polymeric micelles might be a solution to deliver drugs to the place of action compared to conventional formulations. Due to low Z-average (89.92 ± 2.7 nm), a polydispersity index of 0.216 ± 0.014 and high surface polarity (52.23%), a significant increase in water solubility (14-fold) was experienced. This increase resulted in favourable dissolution profile at nasal and axonal conditions with high in vitro permeability value (14.6×10-6 cm/s) on polar brain (porcine) lipid extract. Modified Side-bi-side® type diffusion study confirmed rapid and efficient passive diffusion through the nasal mucosa contributed by strong mucoadhesive properties. The final formulation met all the requirements of a nasal drug delivery system with rapid onset of action, meaning DXM can reach the CNS and there it can exert its beneficial effects in pathological conditions.


Assuntos
Portadores de Fármacos , Micelas , Animais , Dexametasona , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Polímeros , Solubilidade , Suínos
12.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445587

RESUMO

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Microesferas , Fragmentos de Peptídeos/administração & dosagem , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas/administração & dosagem , Animais , Composição de Medicamentos , Humanos , Fragmentos de Peptídeos/química , Proteínas/química
13.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361825

RESUMO

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.


Assuntos
Córnea/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/administração & dosagem , Segmento Posterior do Olho/metabolismo , Compostos de Espiro/administração & dosagem , Animais , Córnea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Segmento Posterior do Olho/efeitos dos fármacos , Coelhos , Compostos de Espiro/química
14.
Anal Chem ; 93(34): 11751-11757, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34398599

RESUMO

Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Ácidos Nucleicos , Diagnóstico por Imagem , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
15.
J Biomed Nanotechnol ; 17(7): 1320-1329, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446135

RESUMO

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the availablematerials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-ß-cyclodextrin. Notably, when peptide C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of PLGA NPs. Therefore, we suggest this peptide as a promising surface modification agent for enhancing drug delivery to cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy.


Assuntos
Peptídeos Penetradores de Células , Nanopartículas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Glicolatos , Glicóis , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
16.
Anal Chem ; 93(32): 11275-11283, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34342424

RESUMO

Accurate diagnosis and targeted therapy are essential to precision theranostics. However, nonspecific response of theranostic agents in healthy tissues impedes their practical applications. Here, we design an activatable DNA nanosphere for specifically in situ sensing of cancer biomarker flap endonuclease 1 (FEN1) and spatiotemporally modulating drug release. The gold nanostar-conjugated FEN1 substrate acts as spherical nucleic acid and induces a fluorescence signal upon a FEN1 stimulus for diagnosis. Guided by the nanoflare, external NIR light then triggers a controlled release of carried drugs at desired sites. This DNA nanosphere not only exhibits good stability, sensitivity, and specificity toward FEN1 assay but also serves as a precision theranostic agent for targeted and controlled drug delivery. Our study provides a reliable method for FEN1 imaging in vitro and in vivo and suggests a powerful strategy for precision medicine.


Assuntos
Neoplasias , Ácidos Nucleicos , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Endonucleases Flap , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
17.
ACS Biomater Sci Eng ; 7(9): 4509-4520, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34346208

RESUMO

Searching for drug carries with controlled release and good biocompatibility has always been one of the research hotspots and difficulties. Herein, core-sheath nanofibrous mats (NFs) consisting of biocompatible poly(ethylene oxide) (PEO, core) and poly(l-lactic acid) (PLLA, sheath) for drug delivery were fabricated via coaxial electrospinning strategy. The nontoxic layered silicate rectorite (REC) with 0.5-1 wt % amount was introduced in the sheath for sustained drug delivery. Layered REC could be intercalated with PLLA macromolecule chains, leading to the densified structure for loading and keeping doxorubicin hydrochloride (DOX) while reversibly capturing and releasing DOX to delay the drug migration due to its high cation activity. The addition of REC in NFs could delay the initial burst release of DOX and prolong the residence time from 12 to 96 h. Moreover, DOX-loaded core-sheath NFs had in vitro culture with strong antitumor activity, which was confirmed by cytotoxicity results and live and dead assay. HepG2 tumor-bearing xenograft further demonstrated the tumor-suppression effect and the excellent safety of the DOX-loaded core-sheath NFs in vivo. The constructed NFs as drug carriers showed great potential in the local treatment of solid tumors.


Assuntos
Nanofibras , Silicatos de Alumínio , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Minerais
18.
Biomaterials ; 276: 120919, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34419838

RESUMO

Peptide functionalized hyaluronic acid (HACF) cross-linked by cucurbit[8]uril (CB[8]), a new class of drug-delivery reservoirs, is used to enable improved drug bioavailability for glioblastoma tumors in patient-derived xenograft (PDX) models. The mechanical and viscoelastic properties of native human and mouse tissues are measured over 8 h via oscillatory rheology under physiological conditions. Treatment with drug-loaded hydrogels allowed for a significant survival impact of 45 % (55.5-80.5 days). A relationship between the type of PDX tumor formed-a consequence of the heterogeneic nature of GB tumors-and changes in the initial survival is observed owing to greater local pressure from stiffer tumors. These biocompatible and tailorable materials warrant use as drug delivery reservoirs in PDX resection models, where the mechanical properties can be readily adjusted to match the stiffness of local tissue and thus have potential to improve the survival of GB patients.


Assuntos
Glioblastoma , Animais , Encéfalo , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Humanos , Ácido Hialurônico , Hidrogéis , Camundongos , Reologia
19.
Nanomedicine (Lond) ; 16(21): 1905-1923, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34348474

RESUMO

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Antibacterianos/uso terapêutico , Biofilmes , Sistemas de Liberação de Medicamentos , Pulmão
20.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360729

RESUMO

Mitochondria are considered to be important organelles in the cell and play a key role in the physiological function of the heart, as well as in the pathogenesis and development of various heart diseases. Under certain pathological conditions, such as cardiovascular diseases, stroke, traumatic brain injury, neurodegenerative diseases, muscular dystrophy, etc., mitochondrial permeability transition pore (mPTP) is formed and opened, which can lead to dysfunction of mitochondria and subsequently to cell death. This review summarizes the results of studies carried out by our group of the effect of astaxanthin (AST) on the functional state of rat heart mitochondria upon direct addition of AST to isolated mitochondria and upon chronic administration of AST under conditions of mPTP opening. It was shown that AST exerted a protective effect under all conditions. In addition, AST treatment was found to prevent isoproterenol-induced oxidative damage to mitochondria and increase mitochondrial efficiency. AST, a ketocarotenoid, may be a potential mitochondrial target in therapy for pathological conditions associated with oxidative damage and mitochondrial dysfunction, and may be a potential mitochondrial target in therapy for pathological conditions.


Assuntos
Sistemas de Liberação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Mitocôndrias Cardíacas/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/patologia , Humanos , Isoproterenol/efeitos adversos , Isoproterenol/uso terapêutico , Mitocôndrias Cardíacas/patologia , Oxirredução/efeitos dos fármacos , Xantofilas/uso terapêutico
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