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1.
Nat Commun ; 12(1): 4858, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381048

RESUMO

Complement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento/metabolismo , Dendrímeros/metabolismo , Imunoglobulina M/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C1q/metabolismo , Dendrímeros/química , Dendrímeros/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Humanos , Lectina de Ligação a Manose/metabolismo , Serina Proteases Associadas a Proteína de Ligação a Manose , Poliaminas/química , Poliaminas/metabolismo , Poliaminas/farmacologia
2.
Colloids Surf B Biointerfaces ; 206: 111945, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34216849

RESUMO

The present study aimed to develop Apremilast loaded nanostructured lipid carriers (NLCs) for topical delivery to overcome the limitations of oral therapy and increase the efficacy. Apremilast loaded NLCs were prepared by hot emulsification technique. The developed formulation was optimized by Box Behnken design and characterized for size, entrapment efficiency, and zeta potential. The selected formulation was investigated for in-vitro release, ex-vivo skin retention, dermatokinetic, psoriasis efficacy, in-vivo skin retention and skin irritation study. The NLCs characterization results showed its spherical shape with the particle size of 157.91 ± 1.267 nm (0.165 ± 0.017 PDI). The entrapment efficiency and zeta potential were found to be 69.144 ± 0.278% and -16.75 ± 1.40 mV, respectively. The in-vitro release study revealed a controlled release of Apremilast from NLCs up to 24 h. The ex-vivo study showed 3-fold enhanced skin retention compared to conventional gel preparation. The formulation depicted improved psoriasis efficacy indicating reduced TNF-α mRNA expression. The cytotoxicity and skin irritation study revealed the prepared formulation has no toxicity or irritation. The study depicts the NLCs loaded Apremilast can be explored for the topical delivery for treatment of psoriasis with improved skin retention and efficacy.


Assuntos
Portadores de Fármacos , Nanoestruturas , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Lipídeos , Tamanho da Partícula , Pele/metabolismo , Talidomida/análogos & derivados
3.
Int J Nanomedicine ; 16: 4643-4659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267516

RESUMO

Purpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer. Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor. Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects. Conclusion: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.


Assuntos
Bifidobacterium bifidum/metabolismo , Portadores de Fármacos/metabolismo , Nanopartículas/administração & dosagem , Animais , Linhagem Celular Tumoral , Fluorcarbonetos/química , Humanos , Camundongos , Nanopartículas/uso terapêutico , Poliésteres/química
4.
ACS Appl Mater Interfaces ; 13(24): 29070-29082, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34101411

RESUMO

Two novel stimuli-responsive drug delivery systems (DDSs) were successfully created from bovine serum albumin- or myoglobin-gated upconversion nanoparticle-embedded mesoporous silica nanovehicles (UCNP@mSiO2) via diselenide (Se-Se)-containing linkages. More importantly, multiple roles of each scaffold of the nanovehicles were achieved. The controlled release of the encapsulated drug doxorubicin (DOX) within the mesopores was activated by triple stimuli (acidic pH, glutathione, or H2O2) of tumor microenvironments, owing to the conformation/surface charge changes in proteins or the reductive/oxidative cleavages of the Se-Se bonds. Upon release of DOX, the Förster resonance energy transfer between the UCNP cores and encapsulated DOX was eliminated, resulting in an increase in ratiometric upconversion luminescence for DOX release tracking in real time. The two protein-gated DDSs showed some differences in the drug release performances, relevant to structures and properties of the protein nanogates. The introduction of the Se-Se linkages not only increased the versatility of reductive/oxidative cleavages but also showed less cytotoxicity to all cell lines. The DOX-loaded protein-gated nanovehicles showed the inhibitory effect on tumor growth in tumor-bearing mice and negligible damage/toxicity to the normal tissues. The constructed nanovehicles in a spatiotemporally controlled manner have fascinating prospects in targeted drug delivery for cancer chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Bovinos , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Érbio/química , Feminino , Fluoretos/química , Glutationa/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos C57BL , Mioglobina/química , Mioglobina/metabolismo , Porosidade , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto , Itérbio/química , Ítrio/química
5.
ACS Appl Mater Interfaces ; 13(24): 28802-28817, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34109788

RESUMO

In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA-DOX@PDA-FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA-DOX@PDA-FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas Multifuncionais/química , Acrilamidas/química , Acrilamidas/metabolismo , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Endocitose/fisiologia , Ácido Fólico/análogos & derivados , Ácido Fólico/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Indóis/metabolismo , Indóis/efeitos da radiação , Raios Infravermelhos , Camundongos , Nanopartículas Multifuncionais/metabolismo , Terapia Fototérmica , Polímeros/química , Polímeros/metabolismo , Polímeros/efeitos da radiação , Temperatura
6.
ACS Appl Mater Interfaces ; 13(25): 29416-29423, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34148345

RESUMO

DNA self-assembled nanostructures have been considered as effective vehicles for biomolecule delivery because of their excellent biocompatibility, cellular permeability, noncytotoxicity, and small size. Here, we report an efficient antiviral strategy with self-assembled tetrahedral framework nucleic acids (tFNAs) delivering small interfering RNA (t-siRNA) to silence classical swine fever virus (CSFV) gene in porcine host cells. In this study, two previously reported siRNAs, C3 and C6, specifically targeting the CSFV genome were selected and modified on tFNAs, respectively, and termed t-C3 and t-C6. Results indicate that t-C3 and t-C6 can inhibit the viral proliferation of CSFV in kidney derived porcine cells, PK-15, effectively and that inhibition was markedly stronger than free siRNA-C3 or siRNA-C6 only. In addition, the DNA nanostructure also has high cargo-carrying capacity, allowing to deliver multiple functional groups. To improve the antiviral ability of tFNAs, a dual-targeting DNA nanostructure t-C3-C6 was constructed and used to silence the CSFV gene in porcine host cells. This study found that t-C3-C6 can inhibit the viral release and replication, exhibiting outstanding anti-CSFV capabilities. Therefore, these dual-targeting tFNAs have great potential in virus therapy. This strategy not only provides a novel method to inhibit CSFV replication in porcine cells but also verifies that tFNAs are effective tools for delivery of antiviral elements, which have great application potential.


Assuntos
Antivirais , Vírus da Febre Suína Clássica/efeitos dos fármacos , Portadores de Fármacos , Nanoestruturas/química , RNA Interferente Pequeno , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Suínos , Replicação Viral/efeitos dos fármacos
7.
Ther Deliv ; 12(8): 565-574, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34187177

RESUMO

Background: Nanostructured lipid carriers (NLCs) of fluconazole were prepared to improve permeability and thereby effective topical drug delivery. Materials and methods: NLCs were prepared and evaluated, and then the optimized NLC suspension was incorporated into a gel that was further evaluated for topical drug delivery. Results and discussion: F-2 NLC formulation was optimized based on results of particle size (161.3 ± 1.385 nm), polydispersity index (0.401), zeta potential (-33 ± 0.46), entrapment efficiency (82.26 ± 0.91%) and in vitro drug release (76.40 ± 0.21%). Ex vivo skin permeation studies showed flux of F-2 gel and the comparison marketed gel as 0.21 and 0.18 mg/cm2/h, respectively. The in vitro antifungal study revealed significantly better activity compared with the marketed gel. Conclusion: Fluconazole NLCs increase drug permeability and proved to be effective in topical drug delivery.


Assuntos
Fluconazol , Nanoestruturas , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Fluconazol/metabolismo , Lipídeos , Tamanho da Partícula , Pele/metabolismo
8.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067699

RESUMO

Gene therapy has the potential to become a staple of 21st-century medicine. However, to overcome the limitations of existing gene-delivery therapies, that is, poor stability and inefficient and delivery and accumulation of nucleic acids (NAs), safe drug-delivery systems (DDSs) allowing the prolonged circulation and expression of the administered genes in vivo are needed. In this review article, the development of DDSs over the past 70 years is briefly described. Since synthetic DDSs can be recognized and eliminated as foreign substances by the immune system, new approaches must be found. Using the body's own cells as DDSs is a unique and exciting strategy and can be used in a completely new way to overcome the critical limitations of existing drug-delivery approaches. Among the different circulatory cells, red blood cells (RBCs) are the most abundant and thus can be isolated in sufficiently large quantities to decrease the complexity and cost of the treatment compared to other cell-based carriers. Therefore, in the second part, this article describes 70 years of research on the development of RBCs as DDSs, covering the most important RBC properties and loading methods. In the third part, it focuses on RBCs as the NA delivery system with advantages and drawbacks discussed to decide whether they are suitable for NA delivery in vivo.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Eritrócitos/metabolismo , Portadores de Fármacos/metabolismo , Eritrócitos/fisiologia , Humanos , Nanopartículas/administração & dosagem , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Preparações Farmacêuticas/metabolismo
9.
AAPS PharmSciTech ; 22(5): 171, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34100170

RESUMO

Macrophages act as a cellular reservoir in HIV infection. Elimination of HIV from macrophages has been an unfulfilled dream due to the failure of drugs to reach them. To address this, we developed CD44 receptor-targeted, novel hyaluronic acid (HA)-coated nanostructured lipid carriers (NLCs) of efavirenz via washless layer-by-layer (LbL) assembly of HA and polyallylamine hydrochloride (PAH). NLCs were subjected to TEM analysis, size and zeta potential, in vitro release and encapsulation efficiency studies. The uptake of NLCs in THP-1 cells was studied using fluorescence microscopy and flow cytometry. The anti-HIV efficacy was evaluated using p24 antigen inhibition assay. NLCs were found to be spherical in shape with anionic zeta potential (-23.66 ± 0.87 mV) and 241.83 ± 5.38 nm particle size. NLCs exhibited prolonged release of efavirenz during in vitro drug release studies. Flow cytometry revealed 1.73-fold higher uptake of HA-coated NLCs in THP-1 cells. Cytotoxicity studies showed no significant change in cell viability in presence of NLCs as compared with the control. HA-coated NLCs distributed throughout the cell including cytoplasm, plasma membrane and nucleus, as observed during fluorescence microscopy. HA-coated NLCs demonstrated consistent and significantly higher inhibition (81.26 ± 1.70%) of p24 antigen which was 2.08-fold higher than plain NLCs. The obtained results suggested preferential uptake of HA-coated NLCs via CD44-mediated uptake. The present finding demonstrates that HA-based CD44 receptor targeting in HIV infection is an attractive strategy for maximising the drug delivery to macrophages and achieve effective viral inhibition.


Assuntos
Portadores de Fármacos/administração & dosagem , HIV-1/efeitos dos fármacos , Receptores de Hialuronatos , Macrófagos/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Alcinos/administração & dosagem , Alcinos/síntese química , Alcinos/metabolismo , Benzoxazinas/administração & dosagem , Benzoxazinas/síntese química , Benzoxazinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ciclopropanos/administração & dosagem , Ciclopropanos/síntese química , Ciclopropanos/metabolismo , Relação Dose-Resposta a Droga , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Células HEK293 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , HIV-1/fisiologia , Humanos , Receptores de Hialuronatos/metabolismo , Lipídeos/administração & dosagem , Lipídeos/síntese química , Macrófagos/metabolismo , Nanoestruturas/química , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/metabolismo , Células THP-1
10.
ACS Appl Mater Interfaces ; 13(20): 23384-23395, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33982571

RESUMO

Construction of multifunctional nonviral gene vectors to execute defined tasks holds great potential for the precise and effective treatment of gene-associated diseases. Herein, we have developed four large π-conjugation triphenylamine derivatives bearing two polar [12]aneN3 heads and a lipophilic tail for applications in gene delivery, one/two-photon-triggered near-infrared (NIR) fluorescence bioimaging, and combined photodynamic therapy (PDT) and gene therapy of cancer. These compounds possess typical NIR aggregation-induced emission characteristics, mega Stokes shifts, strong two-photon excitation fluorescence, and excellent DNA condensation abilities. Among them, vector 4 with a tail of n-hexadecane realized a transfection efficiency as high as 6.7 times that of the commercial transfection agent Lipofectamine 2000 in HEK293T cell lines. Using vector 4 as an example, transfection process tracking and ex vivo/in vivo tumoral imaging and retention with high resolution, high brightness, deep tissue penetration, and good biosafety were demonstrated. In addition, efficient singlet oxygen (1O2) generation by the DNA complex formed by vector 4 (4/DNA) resulted in effective PDT. Combined with anticancer gene therapy, collaborative cancer treatment with a dramatically enhanced cancer cell-killing effect was achieved. The development of this "three birds, one stone" approach suggests a new and promising strategy for better cancer treatment and real-time tracking of gene delivery.


Assuntos
Antineoplásicos , Corantes Fluorescentes , Vetores Genéticos , Nanomedicina Teranóstica/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Terapia Genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Espectroscopia de Luz Próxima ao Infravermelho
11.
AAPS PharmSciTech ; 22(5): 164, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34041632

RESUMO

Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis include methotrexate (MTX), cyclosporine (CsA), acitretin, dexamethasone, and salicylic acid. However, conventional formulations due to poor absorptive capacity, inconsistent drug release characteristics, poor capability of selective targeting, poor retention of drug molecules in target tissue, and unintended skin reactions restrict the clinical efficacy of drugs. Advances in topical nanocarriers allow the development of prominent drug delivery platforms can be employed to address the critical issues associated with conventional formulations. Advances in nanocarriers design, nano-dimensional configuration, and surface functionalization allow formulation scientists to develop formulations for a more effective treatment of psoriasis. Moreover, interventions in the size distribution, shape, agglomeration/aggregation potential, and surface chemistry are the significant aspects need to be critically evaluated for better therapeutic results. This review attempted to explore the opportunities and challenges of current revelations in the nano carrier-based topical drug delivery approach used for the treatment of psoriasis.


Assuntos
Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/tendências , Nanocápsulas/administração & dosagem , Psoríase/tratamento farmacológico , Administração Cutânea , Animais , Ciclosporina/administração & dosagem , Ciclosporina/metabolismo , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Humanos , Lipossomos/administração & dosagem , Lipossomos/metabolismo , Metotrexato/administração & dosagem , Metotrexato/metabolismo , Psoríase/metabolismo , Ácido Salicílico/administração & dosagem , Ácido Salicílico/metabolismo
12.
Biosci Biotechnol Biochem ; 85(6): 1405-1414, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33791772

RESUMO

Polyhistidine peptides (PHPs), sequences comprising only histidine residues (>His8), are effective cell-penetrating peptides for plant cells. Using PHP-fusion proteins, we aimed to deliver proteins into cultured plant cells from Nicotiana tabacum, Oryza sativa, and Cryptomeria japonica. Co-cultivation of cultured cells with fusion proteins combining maltose-binding protein (MBP), red fluorescent protein (RFP), and various PHPs (MBP-RFP-His8-His20) in one polypeptide showed the cellular uptake of fusion proteins in all plant cell lines. Maximum intracellular fluorescence was shown in MBP-RFP-His20. Further, adenylate cyclase (CyaA), a synthase of cyclic adenosine monophosphate (cAMP) activated by cytosolic calmodulin, was used as a reporter for protein delivery in living cells. A fusion protein combining MBP, RFP, CyaA, and His20 (MBP-RFP-CyaA-His20) was delivered into plant cells and increased intracellular fluorescence and cAMP production in all cell lines. The present study demonstrates that PHPs are effective carriers of proteins into the intracellular space of various cultured plant cells.


Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Histidina/química , Peptídeos/química , Peptídeos/metabolismo , Células Vegetais/metabolismo , Proteínas Recombinantes de Fusão/química , Transporte Biológico , Linhagem Celular , Membrana Celular/metabolismo , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo
13.
Bioconjug Chem ; 32(5): 950-957, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33861579

RESUMO

We previously reported an approach for intracellular protein delivery by attenuating membrane-lytic activity of cationic amphiphilic peptides on cell surfaces. HAad is one such peptides that cytosolically delivers proteins of interest, including antibodies, by stimulating their endosomal escape. Additionally, HAad elicits ruffling of cell membrane, accompanied by transient membrane permeabilization, allowing for the efficient cytosolic translocation of proteins. In this study, we prepared a conjugate of HAad with pyrenebutyric acid as a membrane-anchoring unit (pBu-HAad). pBu-HAad demonstrated protein delivery into cells with only 1/20 concentration of HAad. However, the conjugates with cholesteryl hemisuccinate and aliphatic fatty acids (C = 3, 6, and 10) did not yield such marked effects. The results of time-course and inhibitor studies suggest that the membrane anchoring of HAad by a pyrene moiety leads to enhanced peptide-membrane interaction and to loosen lipid packing, thus facilitating cytosolic translocation through membranes.


Assuntos
Membrana Celular/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Espaço Intracelular/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Proteínas/metabolismo , Pirenos/química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endossomos/metabolismo , Células HeLa , Humanos , Proteínas/química
14.
Colloids Surf B Biointerfaces ; 203: 111748, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33853001

RESUMO

The advent of nanocarriers in the field of pharmaceutical drug delivery, while exhibiting considerable advantages, has created challenges for researchers. Among the applications of nanocarriers, drug delivery to the skin has attracted increasing attention in recent decades due to its advantages over oral and parenteral administration. Accordingly, this work attempts to discuss the major obstacles surrounding topically applied formulations and different nanocarriers' potential to overcome these barriers to investigate whether their passive penetration through the skin is likely. Therefore, skin anatomical views and transcutaneous pathways are briefly reviewed. Factors commonly thought to influence skin penetration are discussed from the perspective of particularly penetrating nanocarriers. The formulation of these nanocarriers is outlined, and promising constituents are highlighted to help investigators optimize nanocarrier formulations.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Administração Cutânea , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/metabolismo , Pele/metabolismo , Absorção Cutânea
15.
Langmuir ; 37(14): 4137-4146, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33813823

RESUMO

Hydroxyapatite (HA) is the main inorganic component of human bones and teeth. It has good biocompatibility and bioactivity, which promotes its good application prospects in the field of bone drug carriers. In this study, tetraethylenepentamine-graphene (rGO-TEPA)/CaCO3:HA composite microspheres were prepared via microwave hydrothermal synthesis using rGO-TEPA/CaCO3 solid microspheres as intermediates. Furthermore, the incompletely transformed CaCO3 was removed by soaking in a citric acid buffer to obtain rGO-TEPA/HA hollow composite microspheres. The two types of as-prepared composite microspheres exhibited sea urchin-like structures, large BET surface areas, and good dispersibility. Mouse preosteoblast cells (MC3T3-E1) were used for in vitro cytotoxicity experiments. The in vitro cell viability test showed that the two composite drug carriers exhibited noncytotoxicity. Moreover, the doxorubicin (DOX) loading and releasing investigations revealed that the two types of prepared carriers had mild storage-release behaviors and good pH responsiveness. Hence, these rGO-TEPA/HA hollow microspheres have promising applications as bone drug carriers.


Assuntos
Materiais Biomiméticos , Osso e Ossos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Durapatita , Grafite , Microesferas , Ouriços-do-Mar , Animais , Osso e Ossos/citologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Etilenodiaminas , Concentração de Íons de Hidrogênio , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
16.
Int J Pharm ; 602: 120609, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33901597

RESUMO

When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 µm. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400-600 nm, 2, and 7 µm, respectively), and the potential of which as vehicles for topical delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400-600 nm) in furrows at depths of about 25 µm, also after rinsing, while larger particles (7 µm) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.


Assuntos
Portadores de Fármacos , Nanopartículas , Disponibilidade Biológica , Biofarmácia , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Pele/metabolismo
17.
J Sci Food Agric ; 101(13): 5627-5635, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33713049

RESUMO

BACKGROUND: Nanoparticles can improve the bioavailability of bioactive compounds. Concomitant intake of food can affect pharmacokinetic profiles by altering dissolution, absorption, metabolism, and elimination behavior. Studies on the effects of food and its supplements on the bioavailability of bioactives in nanoformulations are few. In this study, the effects of typical food (milk, sugar, high-fat diet, and regular kibble) and a widely consumed probiotic [Bifidobacterium lactis Bb-12® (Bb-12)] on the bioavailability of curcumin in four formulations [simply suspended curcumin (Cur-SS) and curcumin in nanoemulsions (Cur-NEs), in single-walled carbon nanotubes (Cur-SWNTs), and in nanostructured lipid carriers (Cur-NLCs)] were investigated. RESULTS: Fasting treatment and sugar co-ingestion can significantly enhance the bioavailability of curcumin in Cur-NEs and Cur-SWNTs, respectively. Compared with the fasting treatment, co-ingestion with regular kibble reduced the absorption of curcumin in Cur-NEs and Cur-SWNTs. Ingesting milk along with Cur-NE is also not recommended. The mechanisms behind these phenomena were briefly discussed. This study revealed for the first time that the intestinal colonization of Bb-12 reduces the bioavailability of curcumin and this reduction can be attenuated by nanoformulations SWNTs and NLCs, but not NEs. The reason for this difference was the protective effects of the former two nanoformulations against curcumin degradation by Bb-12 according to in vitro experiments. CONCLUSION: Dietary status (including supplementary probiotics) can dramatically influence the bioavailability of curcumin in nanoformulations. © 2021 Society of Chemical Industry.


Assuntos
Curcumina/química , Composição de Medicamentos/métodos , Gorduras/metabolismo , Leite/metabolismo , Probióticos/química , Animais , Bifidobacterium animalis/química , Disponibilidade Biológica , Bovinos , Curcumina/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Gorduras/química , Camundongos , Camundongos Endogâmicos BALB C , Leite/química , Nanopartículas/química , Nanotubos de Carbono/química , Tamanho da Partícula , Probióticos/metabolismo , Solubilidade
18.
ACS Appl Mater Interfaces ; 13(9): 11195-11204, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33645961

RESUMO

Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανß3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανß3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Neoplasias/tratamento farmacológico , Oligopeptídeos/química , Animais , Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Endocitose/fisiologia , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/metabolismo , Camundongos Endogâmicos ICR , Neoplasias/patologia , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Estudo de Prova de Conceito , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Clin Immunol ; 226: 108712, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684527

RESUMO

In the past year, an emerging disease called Coronavirus disease 2019 (COVID-19), caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been discovered in Wuhan, China, which has become a worrying pandemic and has challenged the world health system and economy. SARS-CoV-2 enters the host cell through a specific receptor (Angiotensin-converting enzyme 2) expressed on epithelial cells of various tissues. The virus, by inducing cell apoptosis and production of pro-inflammatory cytokines, generates as cytokine storm, which is the major cause of mortality in the patients. This type of response, along with responses by other immune cell, such as alveolar macrophages and neutrophils causes extensive damage to infected tissue. Newly, a novel cell-based therapy by Mesenchymal stem cell (MSC) as well as by their exosomes has been developed for treatment of COVID-19 that yielded promising outcomes. In this review study, we discuss the characteristics and benefits of MSCs therapy as well as MSC-secreted exosome therapy in treatment of COVID-19 patients.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Exossomos/metabolismo , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Medicina de Precisão/métodos , Linfócitos B/imunologia , COVID-19/tratamento farmacológico , COVID-19/patologia , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Pandemias , SARS-CoV-2/patogenicidade , Linfócitos T/imunologia
20.
Int J Biol Macromol ; 176: 47-65, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33581206

RESUMO

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Glaucoma/tratamento farmacológico , Administração Oftálmica , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Quitosana/metabolismo , Lentes de Contato , Lesões da Córnea/tratamento farmacológico , Portadores de Fármacos/metabolismo , Humanos , Lubrificantes Oftálmicos/administração & dosagem , Lubrificantes Oftálmicos/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Muramidase/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/ultraestrutura , Agentes Molhantes/administração & dosagem , Agentes Molhantes/química , Cicatrização/efeitos dos fármacos
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