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1.
Int J Nanomedicine ; 15: 4363-4392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606683

RESUMO

With continual rapid developments in the biomedical field and understanding of the important mechanisms and pharmacokinetics of biological molecules, controlled drug delivery systems (CDDSs) have been at the forefront over conventional drug delivery systems. Over the past several years, scientists have placed boundless energy and time into exploiting a wide variety of excipients, particularly diverse polymers, both natural and synthetic. More recently, the development of nano polymer blends has achieved noteworthy attention due to their amazing properties, such as biocompatibility, biodegradability and more importantly, their pivotal role in controlled and sustained drug release in vitro and in vivo. These compounds come with a number of effective benefits for improving problems of targeted or controlled drug and gene delivery systems; thus, they have been extensively used in medical and pharmaceutical applications. Additionally, they are quite attractive for wound dressings, textiles, tissue engineering, and biomedical prostheses. In this sense, some important and workable natural polymers (namely, chitosan (CS), starch and cellulose) and some applicable synthetic ones (such as poly-lactic-co-glycolic acid (PLGA), poly(lactic acid) (PLA) and poly-glycolic acid (PGA)) have played an indispensable role over the last two decades for their therapeutic effects owing to their appealing and renewable biological properties. According to our data, this is the first review article highlighting CDDSs composed of diverse natural and synthetic nano biopolymers, blended for biological purposes, mostly over the past five years; other reviews have just briefly mentioned the use of such blended polymers. We, additionally, try to make comparisons between various nano blending systems in terms of improved sustained and controlled drug release behavior.


Assuntos
Preparações de Ação Retardada/farmacologia , Nanopartículas/química , Polímeros/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química
2.
PLoS One ; 15(6): e0234544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555670

RESUMO

Controlled-release and slow-release fertilizers can effectively supply nitrogen (N) while mitigating N loss. To determine the suitability of these fertilizers for plants in semi-arid environments, these fertilizers need to be evaluated under varying placement and temperature conditions. Several urea fertilizers were evaluated, including: uncoated, sulfur-coated (SCU), polymer-coated-sulfur-coated (PCSCU), and polymer-coated (PCU) with projected release timings between 45 and 180 d. Nitrogen release was measured under daily fluctuating or static temperatures applied either to the surface or buried in the soil. A second experiment consisted of two PCU sources and added a hanging bag placement comparison and low and high soil moisture treatments. For the first Experiment, the N in uncoated urea released shortly after application. The SCU and PCSCU treatments released > 80% of the N before the first sampling date. With fluctuating temperatures, the PCU 45, 75, 120, and 180 incorporated into the soil released N within +9, +9, -22, and -68 d of their expected timing. However, they released their N within 35 d when surface applied. Conversely, with static temperatures, PCU products released slowly, releasing under 80% for the entire study. The second experiment verified these results and showed no difference between low and high moisture and minimal release with fertilizer not in contact with soil. Each coated fertilizer in these studies exhibited slow/control release properties, but the PCU (surface applied) and SCU/PCSCU (surface applied or incorporated in soil) release was much more rapid than expected. Our research suggests that, although the SCU and PCSCU showed minimal slow-release properties (regardless of placement), the PCU fertilizers incorporated in the soil do have a controlled release approximate to what is expected, but have a much more rapid release when surface applied.


Assuntos
Agricultura , Preparações de Ação Retardada/farmacologia , Fertilizantes , Nitrogênio/farmacologia , Preparações de Ação Retardada/química , Nitrogênio/química , Polímeros/química , Solo/química , Enxofre/química , Temperatura , Ureia/química , Ureia/farmacologia
3.
Cancer Immunol Immunother ; 69(9): 1737-1749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32333082

RESUMO

Combination immunotherapy targeting the PD-1 and CTLA-4 checkpoint inhibitor pathways provides substantial clinical benefit in patients with advanced-stage cancer but at the risk of dose-limiting inflammatory and autoimmune toxicity. The delicate balance that exists between unleashing tumor killing and promoting systemic autoimmune toxicity represents a major clinical challenge. We hypothesized that targeting anti-CTLA-4 so that it perfuses tumor-draining lymph nodes would provide a significant therapeutic advantage and developed an injectable hydrogel with controlled antibody release characteristics for this purpose. Injection of hydrogel-encapsulated anti-CTLA-4 at a peri-tumor location (MC-38 tumor model) produced dose-dependent antitumor responses and survival that exceeded those by anti-CTLA-4 alone (p < 0.05). Responses to 100 µg of targeted anti-CTLA-4 also equaled or exceeded those observed with a series of systemic injections delivering 600 µg (p < 0.05). While preserving antitumor activity, this approach resulted in serum anti-CTLA-4 exposure (area under the curve) that averaged only 1/16th of that measured with systemic therapy. Consistent with the marked differences in systemic exposure, systemic anti-CTLA-4 stimulated the onset of autoimmune thyroiditis in iodide-exposed NOD.H-2h4 mice, as measured by anti-thyroglobulin antibody titer, while hydrogel-encapsulated anti-CTLA-4 had a minimal effect (p ≤ 0.01). At the same time, this targeted low-dose anti-CTLA-4 approach synergized well with systemic anti-PD-1 to control tumor growth and resulted in a high frequency of complete responders that were immune to tumor re-challenge at a distant site. We conclude that targeted and controlled delivery of low-dose anti-CTLA-4 has the potential to improve the benefit-risk ratio associated with combination checkpoint inhibitor therapy.


Assuntos
Antineoplásicos/farmacologia , Antígeno CTLA-4/imunologia , Preparações de Ação Retardada/farmacologia , Imunidade/efeitos dos fármacos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Autoimunidade/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Sinergismo Farmacológico , Feminino , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD
4.
PLoS One ; 15(2): e0228908, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32107483

RESUMO

The aim of the current study was to develop membrane-based transdermal patches of lornoxicam gel using oleic acid (OA)and propylene glycol (PG) as penetration enhancers to improve drug delivery across the skin and to evaluate in vivo analgesic and anti-inflammatory activity. For this purpose, nine formulations were developed in accordance with 32 factorial design using Design Expert® 11. The concentration of propylene glycol (X1) and oleic acid (X2) were selected as independent variable whereas Q10 (Y1), flux (Y2) and lag time (Y3) were considered as the response variables. The impact of drug loading, surface area, gel concentration, membrane variation and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction, analgesic activity and anti-inflammatory action of the optimized patch were also determined in Albino Wistar rats. Stability studies were performed for three months at three different temperature conditions. The result suggests that a membrane-based system with controlled zero-order drug release of 95.8 ± 1.121% for 10 h exhibiting flux of 126.51±1.19 µg/cm2/h and lag time of 0.908 ±0.57h was optimized with the desired analgesic and anti-inflammatory effect can be obtained by using propylene glycol and oleic acid co-solvents as a penetration enhancer. The patch was also found stable at 4˚C for a period of 6.44 months. Formulation F9 comprising of 10% PG and 3% OA was selected as an optimized formulation. The study demonstrates that the fabricated transdermal system of lornoxicam can deliver the drug through the skin in a controlled manner with desired analgesic and anti-inflammatory activity and can be considered as a suitable alternative of the oral route.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Piroxicam/análogos & derivados , Administração Cutânea , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Química Farmacêutica , Preparações de Ação Retardada/farmacologia , Géis/metabolismo , Masculino , Ácido Oleico/farmacologia , Piroxicam/farmacologia , Propilenoglicol/farmacologia , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea/fisiologia , Solventes/farmacologia , Adesivo Transdérmico
5.
Int J Nanomedicine ; 15: 1239-1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110020

RESUMO

Introduction: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy. Methods: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model. Results: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles. Conclusion: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Curcumina/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Linhagem Celular Tumoral , Curcumina/farmacologia , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Ácido Fólico/química , Camundongos Endogâmicos BALB C , Micelas , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Ratos
6.
Mater Sci Eng C Mater Biol Appl ; 108: 110466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923948

RESUMO

Essentially, the human body can release in different disease conditions specific biomolecules such as histamines when the body encounters a toxic substance, antibodies which are part of the body's natural immune response or nitric oxide as a cardiovascular signalling molecule. Design and development of "intelligent" delivery systems able to release the therapeutic agent only in the presence of bioactive compounds was presented here. Poly(N-isopropylacrylamide-co-N-(3-aminopropyl)methacrylamide)) (poly(NIPAAm-co-APM)) was synthesized as an exciting pH/temperature sensitive copolymer. Under physiological conditions (pH = 7.4), the APM in copolymer is in the ionized state (pKa = 8.7), highly hydrophilic and therefore the copolymer loses thermosensitive properties. Remarkably, after electrostatic interactions of APM with specific biomolecules, the copolymer restores the thermosensitive property. Thus, the microgels synthesized from this copolymer are in the "inactivated" state at normal physiological pH and temperature (pH = 7.4 and T = 36 °C). In the presence of specific biomolecules, microgels undergo "activation", shrink and expel mechanically a certain amount of drug. It must be mentioned that the pH-sensitive component plays the role of a biosensor, the biomolecule acts as a triggering agent, and the poly(NIPAAm) represents the delivery component (actuator). MTT tests showed that poly(NIPAAm-co-APM) microspheres are completely devoid of toxicity; moreover, the rabbit dermal fibroblasts vastly adhere to the surface of microspheres.


Assuntos
Derme/metabolismo , Portadores de Fármacos , Fibroblastos/metabolismo , Teste de Materiais , Animais , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Derme/citologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fibroblastos/citologia , Concentração de Íons de Hidrogênio , Coelhos
7.
Mater Sci Eng C Mater Biol Appl ; 108: 110432, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923974

RESUMO

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and inner diameter of 180 ± 48 nm and 106 ± 30 nm, respectively. Thermal gravimetric analysis determines that the mass loss of the core-sheath fibers fall between the mass loss values of individual sheath and core fibers. Swelling studies indicate higher water absorption of the core-sheath mat compared to the separate sheath and core membranes. In vitro drug release studies in Phosphate Buffered Saline (PBS) determine sustained release of the therapeutics from the core-sheath structure. The release trails three stages including non-Fickian diffusion at the early stage followed by the Fickian diffusion mechanism. The present study shows a useful approach to design core-sheath nanofibrous membranes with controlled and programmable drug release profiles.


Assuntos
Gelatina , Muramidase , Nanofibras/química , Fenitoína , Álcool de Polivinil , Animais , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Gelatina/química , Gelatina/farmacologia , Camundongos , Muramidase/química , Muramidase/farmacocinética , Muramidase/farmacologia , Fenitoína/química , Fenitoína/farmacocinética , Fenitoína/farmacologia , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia
8.
Mater Sci Eng C Mater Biol Appl ; 108: 110461, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924029

RESUMO

A novel bio-responsive co-delivery system based on Poly(DEA)-b-Poly(ABMA-co-OEGMA) (PDPAO, prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization) copolymers was constructed for enhanced cellular internalization and effective combination therapy. Reduction-sensitive 6-mercaptopurine (6MP) based prodrug and pH-sensitive doxorubicin (DOX) based prodrug were grafted onto PDPAO by an azide-alkyne "Click Chemistry" reaction to acquire a pH/reduction-sensitive polymeric prodrug (PDPAO@imine-DOX/cis-6MP), which was able to self-aggregate to form polymeric micelles (M(DOX/6MP)) with an average particle size of 116 ± 2 nm in the water. The resultant micelles could maintain a stable sphere structure and show stability with a small particles' dispersion index in the blood. Importantly, it has been observed that the pH-sensitive surface charge-conversion accompanied pH-triggered DOX release in the biomimetic extracellular acidic environment of tumor tissue and a rapid dual-drug release triggered by pH and GSH in the intracellular environment. The in vitro evaluation of micelles on human cervical cancer (HeLa) and human promyelocytic leukemia (HL-60) cells showed an enhanced cellular uptake because of charge-conversion and exhibited a higher cell-killing performance. Moreover, the graft ratio of DOX and 6MP showed the ability to adjust the cytotoxicity; the micelles with a graft ratio of 2: 1 (M(DOX2/6MP)) displayed the higher cellular inhibition on either HeLa (combination index (CI) = 0.62) or HL-60 (CI = 0.35) cells. Overall, this novel dual-drug-conjugated delivery system might have important potential applications for combination therapy of cancer.


Assuntos
Química Click , Doxorrubicina , Portadores de Fármacos , Mercaptopurina , Neoplasias/tratamento farmacológico , Pró-Fármacos , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células HL-60 , Células HeLa , Humanos , Mercaptopurina/química , Mercaptopurina/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia
9.
Mater Sci Eng C Mater Biol Appl ; 108: 110459, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924031

RESUMO

In this work, a new pH-responsive nanohybrid carrier was prepared with chelating ZnO-dopamine (Zn-d) on the surface of graphene oxide. Doxorubicin (DOX) as a model drug was loaded on the resulted nanohybrid. The characteristics of Zn-d-rGO nanohybrid (NH) determined using Fourier transformed infrared spectroscopy (FT-IR), X-ray Diffraction spectroscopy (XRD), UV-Visible spectroscopy, Scanning Electron Microscope (SEM), EDX and AFM. The BET analysis showed a specific surface area of 37.16 m2/g and the obtained nanohybrid indicated a high loading capacity of DOX up to 99.7%, and the release profile displayed a pH-dependent discharge in the acidic environment for14 days. The cytotoxicity of the prepared nanohybrid was measured against T47D and MCF10A cells and it confirmed that as-prepared nanohybrid has high toxicity against cancer cells and lower effect against human breast cell. Meanwhile, the prepared nanohybrids showed well antimicrobial activity against gram-positive and negative bacteria. The obtained results showed that the prepared nanohybrid (Zn-d-rGO) could potentially be used as a safe carrier for drug delivery systems.


Assuntos
Antibacterianos , Quelantes , Dopamina , Doxorrubicina , Portadores de Fármacos , Grafite , Nanopartículas/química , Óxido de Zinco , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Quelantes/química , Quelantes/farmacocinética , Quelantes/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Dopamina/química , Dopamina/farmacocinética , Dopamina/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Grafite/química , Grafite/farmacocinética , Grafite/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Óxido de Zinco/química , Óxido de Zinco/farmacocinética , Óxido de Zinco/farmacologia
10.
Mater Sci Eng C Mater Biol Appl ; 108: 110455, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924042

RESUMO

An amphiphilic biodegradable branched copolymer, mPEG-b-PLGA-g-OCol, was synthesized by grafting copolymer (methoxy polyethylene glycol)-b-Poly (l,d-lactic-co-glycolic acid) (mPEG-b-PLGA) on oligomeric collagen (OCol), to form a branched structure with mPEG-b-PLGA as side chain and OCol as backbone. mPEG-b-PLGA and mPEG-b-PLGA-g-OCol were both amphipathic and can self-assemble into micelles in aqueous solution. The mPEG-b-PLGA-g-OCol micelles showed pH-sensitive behaviors and the particle size below 100 nm in slightly acidic environment such as tumor tissue milieu interieur to perform passive targeting. Observed by SEM, when the solution pH increased from 5 to 9, the morphology of mPEG-b-PLGA-g-OCol micelles changed from small spheres to larger ones to rings. For biodegradable mPEG-b-PLGA-g-OCol, the micelles will gradually degrade in body. Further, doxorubicin (DOX) was effectively loaded in the micelles with drug loading and encapsulation efficiency of 3.48% and 25.8%, respectively. To evaluate antineoplastic effect of DOX-laden micelles in vitro, MTT test, flow cytometry and CLSM were performed and found that DOX-laden micelles exhibited higher cellular proliferation inhibition against HeLa cells. These features indicated that the mPEG-b-PLGA-g-OCol micelles were potential drug carrier for cancer therapy.


Assuntos
Plásticos Biodegradáveis , Portadores de Fármacos , Micelas , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia
11.
ACS Appl Mater Interfaces ; 12(4): 4295-4307, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904927

RESUMO

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NPs) with negative, positive, and hydrophobic surfaces that were incorporated outside, inside, or between the lipid bilayers, respectively. To characterize how NPs are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NPs are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 °C with high enthalpy 34.8 J/g) avoiding the leakage of the encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100% of cellular uptake was achieved with a high cell survival (above 80%), which is preserved (83%) for doxorubicin-loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 h, leading to a cell survival reduction of 20%. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating to avoid drug degradation. In conclusion, these drug-loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place, efficiently using an external AMF to reduce or even eliminate side effects.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Liberação Controlada de Fármacos , Humanos , Campos Magnéticos , Nanopartículas/química
12.
Mater Sci Eng C Mater Biol Appl ; 108: 110194, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923931

RESUMO

The thermal, physical, and morphological properties of diphenhydraminium ibuprofenate ([DIP][IBU]) adsorbed onto mesoporous silica (SiO2-60 Šand SiO2-90 Å) from solution were determined. The thermal, physical, and morphological properties of [DIP][IBU] supported on silica were determined. The adsorption of [DIP][IBU] on the pores and surface of silica was proven by N2 adsorption/desorption isotherms. Additionally, release profiles were determined for all systems, and the antinociceptive activity of neat [DIP][IBU] and [DIP][IBU] supported on silica were determined. The interaction of [DIP][IBU] and silica was dependent on pore size, with the formation of a [DIP][IBU] monolayer on SiO2-60 and a multilayer on SiO2-90. The release profile was sustained and slow and dependent on the pore size of the silica, in which the smaller the pore size, the faster the release. The nociceptive evaluation showed that [DIP][IBU] presents a greater (99.21 ±â€¯0.85%) antinociceptive effect than the ibuprofen (46 ±â€¯4.3%). Additionally, [DIP][IBU] on SiO2-60 (90 ±â€¯5.8%) had a greater antinociceptive effect than on SiO2-90 (73 ±â€¯13.2%), which indicates that in vivo tests are in accordance with the in vitro experiments.


Assuntos
Analgésicos , Ibuprofeno , Dor/tratamento farmacológico , Dióxido de Silício , Analgésicos/química , Analgésicos/farmacocinética , Analgésicos/farmacologia , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacologia , Masculino , Camundongos , Dor/metabolismo , Dor/fisiopatologia , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/farmacologia
13.
Mater Sci Eng C Mater Biol Appl ; 108: 110337, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923987

RESUMO

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.


Assuntos
Antineoplásicos , Nanocompostos , Neoplasias/tratamento farmacológico , Norfloxacino , Poliésteres , Titânio , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Nanocompostos/química , Nanocompostos/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Norfloxacino/química , Norfloxacino/farmacocinética , Norfloxacino/farmacologia , Células PC-3 , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Titânio/química , Titânio/farmacocinética , Titânio/farmacologia
14.
Mater Sci Eng C Mater Biol Appl ; 108: 110191, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923988

RESUMO

Effective therapeutic delivery of peptide and protein drugs is challenged by short in vivo half-lives due to rapid degradation. Sustained release formulations of αCT1, a 25 amino acid peptide drug, would afford lower dosing frequency in indications that require long term treatment, such as chronic wounds and cancers. In this study, rhodamine B (RhB) was used as a model drug to develop and optimize a double emulsion-solvent evaporation method of poly(lactic-co-glycolic acid) (PLGA) nanoparticle synthesis. Encapsulation of αCT1 in these nanoparticles (NPs) resulted in a sustained in vitro release profile over three weeks, characterized by an initial burst release of approximately 50% of total encapsulated drug over the first three days followed by sustained release over the remaining two and a half weeks. NP uptake by glioblastoma stem cells was through endocytosis and RhB and αCT1 were observed in cells after at least 4 days.


Assuntos
Materiais Biomiméticos , Conexina 43 , Glioblastoma , Nanopartículas , Peptídeos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Linhagem Celular Tumoral , Conexina 43/química , Conexina 43/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia
15.
Carbohydr Polym ; 231: 115714, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888845

RESUMO

Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, ß-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing ß-cyclodextrin trimer (ß-CD3) as the host unit and unmodified curcumin as the guest unit. Due to the adjustment of host-guest inclusion and hydrophilic-hydrophobic interactions occurring in the SSAs, their morphology could be readily tuned by changing the ratio of the two components. Different self-assembly morphologies, such as spherical complex micelles, spindle-like complex micelles and multi-compartment vesicles, were obtained. Furthermore, basic cell experiments were performed to study the corresponding effects of the SSA shape on their biological properties. Compared to the other micelles, the spindle-like complex micelles exhibited enhanced cellular toxicity, uptake behaviors and apoptosis rates, and the spherical complex micelles exhibited poor performance. The performance of the multi-compartment vesicles was similar to that of the spindle-like complex micelles. The facile construction of these shape-regulated SSAs and their different cellular biological properties might be valuable in the controlled drug release field.


Assuntos
Curcumina/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , beta-Ciclodextrinas/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Células MCF-7 , Micelas , Neoplasias , beta-Ciclodextrinas/farmacologia
16.
Metabolism ; 103: 154044, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31812628

RESUMO

BACKGROUND: Skeletal muscle atrophy is characterized by muscle wasting with partial or complete functional loss. Skeletal muscle atrophy severely affects the quality of life and currently, there is no available therapy except for spinal muscular atrophy. OBJECTIVE: Drug repositioning is a promising strategy that reduces cost and time due to prior availability of safety and toxicity details. Here we investigated myogenic and anti-atrophy effects of glucagon-like peptide-1 (GLP-1) analog liraglutide. METHODS: We used several in vitro atrophy models in C2C12 cells and in vivo models in Sprague Dawley rats to study Liraglutide's efficacy. Western blotting was used to assess cAMP-dependent signaling pathways specifically activated by liraglutide. Therapeutic efficacy of liraglutide was investigated by histological analysis of transverse muscle sections followed by morphometry. Myogenic capacity was investigated by immunoblotting for myogenic factors. RESULTS: Liraglutide induced myogenesis in C2C12 myoblasts through GLP-1 receptor via a cAMP-dependent complex network of signaling events involving protein kinase A, phosphoinositide 3-kinase/protein kinase B, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. Liraglutide imparted protection against freeze injury, denervation, and dexamethasone -induced skeletal muscle atrophy and improved muscular function in all these models. In a therapeutic model, liraglutide restored myofibrillar architecture in ovariectomy-induced atrophy. Anti-atrophy actions of liraglutide involved suppression of atrogene expression and enhancement in expression of myogenic factors. CONCLUSION: Liraglutide imparted protection and restored myofibrillar architecture in diverse models of muscle atrophy. Given its potent anti-atrophy, and recently reported osteoanabolic effects, we propose liraglutide's clinical evaluation in skeletal muscle atrophy and musculoskeletal disorders associated with diverse pathologies.


Assuntos
Liraglutida/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Animais , Células Cultivadas , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Liraglutida/uso terapêutico , Masculino , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/fisiologia , Músculo Esquelético/patologia , Mioblastos/efeitos dos fármacos , Mioblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Roedores
17.
Colloids Surf B Biointerfaces ; 185: 110611, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704609

RESUMO

Nanocolloids are considered ideal carriers for hydrophobic drugs owing to their core-shell structure. Lapatinib is a potential anti-cancer agent, but its clinical use is limited because of its poor aqueous solubility, thus requiring larger oral doses with the associated toxicity. Thus, in the present study, we fabricated self-assembled nanocolloidal polymeric micelles (LP-PMs) of Soluplus® and Pluronic® F127 by the thin-film hydration method and assessed their delivery potential of the hydrophobic anti-cancer drug lapatinib (LP) and optimised these nanocolloidal polymeric micelles using Quality-by-Design approach. Amorphisation of the drug and no typical incompatibility other than hydrogen bonding in the LP-PMs was confirmed by solid-state characterisation. The LP-PMs exhibited a uniform size of 92.9 ± 4.07 nm, with a 5.06 mV zeta potential and approximately 87% drug encapsulation. The critical micellar concentration (CMC) of Soluplus® decreased from 6.63 × 10-3 to 4.4 × 10-3 mg/mL by incorporating Pluronic® F127. Further, the sustained release of LP from the LP-PMs was confirmed by in-vitro release studies showing 36% and 60% of LP released from the LP-PMs within 48 h in release media of pH 7.4 and pH 5.0, respectively. These results support their capability of preferential release at acidic tumor environment. Their hemocompatibility evidenced by hemolysis below accepted limits and no platelet aggregation with resistance to instant dilution illustrated their admirable blood compatibility and suitability for intravenous administration. The encapsulation of LP inside micelles enhanced the cytotoxicity of LP against SKBr3 breast cancer cells. Further, the LP-PMs were found to be stable over six months when stored at 2-8 °C. These findings indicate the improved potential of nanocolloidal polymeric micelles as promising carriers for the preferential and sustained delivery of hydrophobic anticancer drugs such as lapatinib to tumours.


Assuntos
Antineoplásicos/farmacologia , Coloides/química , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Lapatinib/farmacologia , Nanopartículas/química , Polietilenoglicóis/farmacologia , Polivinil/farmacologia , Linhagem Celular Tumoral , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Humanos , Micelas , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Colloids Surf B Biointerfaces ; 185: 110608, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707225

RESUMO

Drug content and releasing rate are the main determining factors for the drug delivery systems (DDSs). Here, doxorubicin dimer (D-DOXcar) was synthesized as drug-drug conjugate prodrug with high drug content of 86%, via an acid-triggered hydrolysable carbamate linker. The prodrug nanoparticles (D-DOXcar-NP) with different diameters were prepared as drug self-delivery system (DSDS) for intracellular pH-triggered slow release. They showed size- and concentration-dependent pH-triggered slow DOX release. For the D-DOXcar-sNP with smaller diameter, the cumulative release ratio reached 25.6% at pH 5.0 within 60 h. The MTT results demonstrated that the proposed DSDS showed similar tumor inhibition regardless of carboxylesterases, and an enhanced anti-tumor efficacy on the HepG2 cells in comparison with the free DOX.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Pró-Fármacos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Hidrodinâmica , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanopartículas/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Espectroscopia de Prótons por Ressonância Magnética
19.
Int J Mol Sci ; 20(23)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810352

RESUMO

To overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly(N-isoproplyacrylamide-co-dimethylaminoethylmethacrylate) (P(NIPAM-co-DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved.


Assuntos
Bortezomib/farmacologia , Ácidos Cafeicos/química , Sistemas de Liberação de Medicamentos , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/química , Ácidos Cafeicos/síntese química , Catecóis/química , Catecóis/farmacologia , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Humanos , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/farmacologia , Mieloma Múltiplo/patologia , Polieletrólitos/síntese química , Polieletrólitos/química , Polieletrólitos/farmacologia , Polímeros/síntese química , Polímeros/química , Polímeros/farmacologia
20.
Pak J Pharm Sci ; 32(5): 2155-2162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31813882

RESUMO

The "noni" species of Morinda citrifolia L., is using in traditional medicine in the tropical country for over 2000 years. Noni fruit has come from the Morinda citrifolia tree which is called Rubiaceae, and it is from the coffee family. It is a perennial herb whose ripe fruit has a robust butyric acid smell and flavor. Recently scientists have proven that this fruit has antioxidant and antibiotic properties in vitro. An anthraquinone, damnacanthal, is one of the constituents of Morinda citrifolia. It has been demonstrated to have anti-cancer properties. Damnacanthal has low water solubility and low bioavailability. Formulating of damnacanthal into the biodegradable nanocapsule drug delivery system may increase its bioavailability. Various formulations of damnacanthal would be developed to enable the selection of a dosage form that could offer the provision of the anti-cancer bioactive substance with suitable sustained- or controlled release properties. The efficiency of extraction of damnacanthal will be compared using both conventional and traditional method. Both the damnacanthal and an anthraquinone active compounds extracted from noni roots, are currently being studied in the context of anti-cancer study. Soon, the medical values, bioactivities and nutritional of this fruit can be assessed, especially its anti-cancer activity, this fruit extract could play an outstanding economic role in Malaysia and other tropical countries.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Plásticos Biodegradáveis/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Nanocápsulas/química , Antraquinonas/química , Antioxidantes/química , Neoplasias da Mama/tratamento farmacológico , Feminino , Frutas/química , Humanos , Medicina Tradicional/métodos , Morinda/química , Extratos Vegetais/química , Raízes de Plantas/química
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