Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Future Med Chem ; 12(6): 479-491, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32064939

RESUMO

Aim: The pharmaceutical industry is showing renewed interest in therapeutic peptides. Unfortunately, the chemical synthesis of peptides remains very expensive and problematic in terms of environmental sustainability. Hence, making peptides 'greener' has become a new front line for the expansion of peptide market. Results: We developed a mechanochemical solvent-free peptide bond-forming protocol using standard reagents and nanocrystalline hydroxyapatite as a bio-compatible, reusable inorganic base. The reaction was also conducted under ultra-mild, minimal solvent-grinding conditions, using common laboratory equipment. Conclusion: The efficacy of the described protocol was validated with the convenient preparation of endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2, the endogenous ligand of the µ-opioid receptor, currently regarded as a lead for the discovery of painkillers devoid of harmful side effects.

2.
Int J Biol Macromol ; 143: 126-135, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31805330

RESUMO

Snail mucus is an attractive natural substance, which is increasingly used in cosmetic creams and syrups thanks to its emollient, moisturizing, protective and reparative properties. The aim of the present study was to explore the physicochemical properties of chitosan-based films added with snail mucus extracted from Helix Aspersa Muller. To this aim, chitosan films at different content of snail mucus were fabricated by simple solvent casting technique. The results of X-ray diffraction analyses, tensile mechanical tests, Infrared spectroscopy and thermogravimetry demonstrated that snail mucus addition strongly modifies the properties of chitosan films. In particular, it acted like a plasticizer enhancing films extensibility up to ten times and strongly improving their water barrier and bioadhesion properties, with a trend depending on Snail mucus content. Furthermore, it provides the films with antibacterial properties and enhanced cytocompatibility, yielding materials with tailored properties for specific requirements.

3.
J Funct Biomater ; 10(2)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060308

RESUMO

ß-tricalcium phosphate (ß-TCP) is one of the most common bioceramics, widely applied in bone cements and implants. Herein we synthesized ß-TCP by solid state reaction in the presence of increasing amounts of two biologically active ions, namely strontium and zinc, in order to clarify the structural modifications induced by ionic substitution. The results of X-ray diffraction analysis indicate that zinc can substitute for calcium into a ß-TCP structure up to about 10 at% inducing a reduction of the cell parameters, whereas the substitution occurs up to about 80 at% in the case of strontium, which provokes a linear increase of the lattice constants, and a slight modification into a more symmetric structure. Rietveld refinements and solid-state 31P NMR spectra demonstrate that the octahedral Ca(5) is the site of ß-TCP preferred by the small zinc ion. ATR-FTIR results indicate that zinc substitution provokes a disorder of ß-TCP structure. At variance with the behavior of zinc, strontium completely avoids Ca(5) site even at high concentration, whereas it exhibits a clear preference for Ca(4) site. The infrared absorption bands of ß-TCP show a general shift towards lower wavenumbers on increasing strontium content. Particularly significant is the shift of the infrared symmetric stretching band at 943 cm-1 due to P(1), that is the phosphate more involved in Ca(4) coordination, which further supports the occupancy preference of strontium.

4.
Molecules ; 24(10)2019 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31109143

RESUMO

3D cylindrical layered scaffolds with anisotropic mechanical properties were prepared according to a new and simple method, which involves gelatin foaming, deposition of foamed strips, in situ crosslinking, strip rolling and lyophilization. Different genipin concentrations were tested in order to obtain strips with different crosslinking degrees and a tunable stability in biological environment. Before lyophilization, the strips were curled in a concentric structure to generate anisotropic spiral-cylindrical scaffolds. The scaffolds displayed significantly higher values of stress at break and of the Young modulus in compression along the longitudinal than the transverse direction. Further improvement of the mechanical properties was achieved by adding strontium-substituted hydroxyapatite (Sr-HA) to the scaffold composition and by increasing genipin concentration. Moreover, composition modulated also water uptake ability and degradation behavior. The scaffolds showed a sustained strontium release, suggesting possible applications for the local treatment of abnormally high bone resorption. This study demonstrates that assembly of layers of different composition can be used as a tool to obtain scaffolds with modulated properties, which can be loaded with drugs or biologically active molecules providing properties tailored upon the needs.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Módulo de Elasticidade , Hidroxiapatitas/química , Estrôncio/administração & dosagem , Tecidos Suporte/química , Anisotropia , Osso e Ossos/cirurgia , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Gelatina/química , Cinética , Estrôncio/química , Engenharia Tecidual/métodos
5.
J Cell Physiol ; 234(11): 20046-20056, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30950062

RESUMO

Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß-tricalcium phosphate (Sr-ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham-operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr-ßTCP, Sr-ßTCP + BMCSs, and Sr-ßTCP + ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro-CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr-ßTCP + BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr-ßTCP + BMCSs group with Sr-ßTCP + ADSCs. Radiographical score, based on micro-CT 2D image, highlighted that the Sr-ßTCP + BMCSs group presented a similar fusion to Sr-ßTCP and higher than Sr-ßTCP + ADSCs in both SHAM and OVX animals. Micro-CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr-ßTCP + BMSCs group than Sr-ßTCP and Sr-ßTCP + ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr-ßTCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr-ßTCP + ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs.

6.
J Funct Biomater ; 10(1)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717259

RESUMO

Dicalcium phosphate dihydrate (DCPD) is one of the mineral phases indicated as possible precursors of biological apatites and it is widely employed in the preparation of calcium phosphate bone cements. Herein, we investigated the possibility to functionalize DCPD with aspartic acid (ASP) and poly-aspartic acid (PASP), as models of the acidic macromolecules of biomineralized tissues, and studied their influence on DCPD hydrolysis. To this aim, the synthesis of DCPD was performed in aqueous solution in the presence of increasing concentrations of PASP and ASP, whereas the hydrolysis reaction was carried out in physiological solution up to three days. The results indicate that it is possible to prepare DCPD functionalized with PASP up to a polyelectrolyte content of about 2.3 wt%. The increase of PASP content induces crystal aggregation, reduction of the yield of the reaction and of the thermal stability of the synthesized DCPD. Moreover, DCPD samples functionalized with PASP display a slower hydrolysis than pure DCPD. On the other hand, in the explored range of concentrations (up to 10 mM) ASP is not incorporated into DCPD and does not influence its crystallization nor its hydrolysis. At variance, when present in the hydrolysis solution, ASP, and even more PASP, delays the conversion into the more stable phases, octacalcium phosphate and/or hydroxyapatite. The greater influence of PASP on the synthesis and hydrolysis of DCPD can be ascribed to the cooperative action of the carboxylate groups and to its good fit with DCPD structure.

7.
Int J Pharm ; 554: 245-255, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30423416

RESUMO

In this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone cells response to the composite cements. 10, 20 and 30% w/w of Alendronate (AL) were successfully introduced into microparticles of Cutina HR and Precirol, which were prepared by means of spray-congealing technique. Addition of AL-loaded MPs to the cement composition provoked a lengthening of the setting and of the hardening processes. However, setting times were still in a range useful for clinical applications, except for the cements at the highest Alendronate content. The composite cements displayed a sustained drug release over time. Cements with the best performances in terms of setting, hardening, mechanical properties and drug release were submitted to in vitro tests using a co-culture model of osteoblast and osteoclast. The results showed that the use of MPs to enrich the cement composition with Alendronate provides materials able to inhibit osteoclast viability and activity, while promoting osteoblast viability and earlier differentiation, indicating that the MPs-cements are good delivery systems for bisphosphonates.


Assuntos
Alendronato/administração & dosagem , Cimentos para Ossos/química , Conservadores da Densidade Óssea/administração & dosagem , Fosfatos de Cálcio/química , Alendronato/química , Alendronato/farmacologia , Materiais Biomiméticos/química , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Técnicas de Cocultura , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Humanos , Lipídeos , Microesferas , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos
8.
Mater Sci Eng C Mater Biol Appl ; 95: 355-362, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30573259

RESUMO

PURPOSE: The purpose of this study was to comparatively investigate the posterolateral fusion rate in ovariectomized (OVX) rats using two new bone graft materials: strontium (Sr) substituted hydroxyapatite (HA) nanocrystals and alendronate (AL) functionalized HA nanocrystals. SrHA was synthesized in presence of different Sr concentrations (SrHA5; SrHA10) and HA-AL nanocrystals at increasing bisphosphonate (BP) content (HA-AL7; HA-AL28). METHODS: A posterolateral spinal fusion model in twenty-five Sham operated and in twenty-five OVX female rats was used and materials were bilaterally implanted between transverse processes of lumbar vertebrae. Sham and OVX animals were divided in five groups depending on the material: HA, SrHA5, SrHA10, HA-AL7 and HA-AL28. The assessment of bone fusion was carried out by µCT, histology and histomorphometry. RESULTS: Some gaps between the transverse processes were observed by µCT in OVXHA group, while they were not present in all the other groups. These results were consistent with the histomorphometrical analyses showing that in OVX animals SrHA and HA-AL materials displayed significantly higher BV/TV and Tb.Th and significantly lower Tb.N and Tb.Sp in comparison with HA alone. CONCLUSIONS: Results of this study suggest that in spinal fusion the incorporation of bioactive ions or drugs as Sr and AL improves the biological performance of HA representing a promising strategy especially in osteoporosis patients with high risks of spinal fusion failure. Results also suggest the existence of a Sr and AL dose response effect and that HA containing the highest AL dose could be the candidate biomaterial for spinal fusion in osteoporotic subjects.


Assuntos
Alendronato/química , Artrodese/métodos , Durapatita/química , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Estrôncio/química , Animais , Materiais Biocompatíveis/química , Feminino , Ovariectomia , Ratos
9.
Nanomaterials (Basel) ; 8(6)2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29857541

RESUMO

Functionalization of calcium phosphates for biomedical applications has been proposed as a strategy to enrich the good osteoinductive properties of these materials with specific therapeutic characteristics. Herein, we prepared and characterized hydroxyapatite nanocrystals functionalized with an anticancer agent, (9R)-9-hydroxystearate (HSA), and loaded with an antimicrobial agent, namely silver nanoparticles (AgNPs). Nanocrystals at two different contents of HSA, about 4 and 9 wt %, were prepared via direct synthesis in aqueous solution. Loading with the antibacterial agent was achieved through interaction with different volumes of AgNPs suspensions. The amount of loaded nanoparticles increases with the volume of the AgNPs suspension and with the hydroxystearate content of the nanocrystals, up to about 3.3 wt %. The structural, morphological, and hydrophobic properties of the composite materials depend on hydroxystearate content, whereas they are not affected by AgNPs loading. At variance, the values of zeta potential slightly increase with the content of AgNPs, which exhibit a sustained release in cell culture medium.

10.
Macromol Biosci ; 18(7): e1800096, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29877029

RESUMO

Strontium has a beneficial role on bone remodeling and is proposed for the treatment of pathologies associated to excessive bone resorption, such as osteoporosis. Herein, the possibility to utilize a biomimetic scaffold as strontium delivery system is explored. Porous 3D gelatin scaffolds containing about 30% of strontium substituted hydroxyapatite (SrHA) or pure hydroxyapatite (HA) are prepared by freeze-drying. The scaffolds display a very high open porosity, with an interconnectivity of 100%. Reinforcement with further amount of gelatin provokes a modest decrease of the average pore size, without reducing interconnectivity. Moreover, reinforced scaffolds display reduced water uptake ability and increased values of mechanical parameters when compared to as-prepared scaffolds. Strontium displays a sustained release in phosphate buffered saline: the quantities released after 14 d from as-prepared and reinforced scaffolds are just 14 and 18% of the initial content, respectively. Coculture of osteoblasts and osteoclasts shows that SrHA-containing scaffolds promote osteoblast viability and activity when compared to HA-containing scaffolds. On the other hand, osteoclastogenesis and osteoclast differentiation are significantly inhibited on SrHA-containing scaffolds, suggesting that these systems could be usefully applied for local delivery of strontium in loci characterized by excessive bone resorption.


Assuntos
Materiais Biomiméticos/síntese química , Preparações de Ação Retardada/síntese química , Gelatina/química , Hidroxiapatitas/química , Osteoblastos/efeitos dos fármacos , Estrôncio/farmacologia , Reabsorção Óssea/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cocultura , Liberação Controlada de Fármacos , Humanos , Cinética , Modelos Biológicos , Osteoblastos/citologia , Osteoblastos/fisiologia , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Porosidade , Estrôncio/química , Estrôncio/metabolismo , Engenharia Tecidual , Tecidos Suporte
11.
J Inorg Biochem ; 183: 1-8, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29525694

RESUMO

The chemistry, structure and morphology of the implant surface have a great influence on the integration of an implant material with bone tissue. In this work, we applied Combinatorial Matrix-Assisted Pulsed Laser Evaporation (C-MAPLE) to deposit gradient thin films with variable compositions of Sr-substituted hydroxyapatite (SrHA) and Zn-substituted ß-tricalcium phosphate (ZnTCP) on Titanium substrates. Five samples with different SrHA/ZnTCP composition ratios were fabricated by a single step laser procedure. SrHA was synthesized in aqueous medium, whereas ZnTCP was obtained by reaction at high temperature. Both powders were separately suspended in deionized water, frozen at liquid nitrogen temperature and used as targets for C-MAPLE experiments, which proceed via simultaneous laser vaporization of two distinct material targets. X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy analyses confirmed that the coatings contain the same crystalline phases as the as-prepared powder samples, with a homogeneous distribution of the two phosphates along deposited thin films. Human osteoclast precursor 2T-110 and human osteoblast-like cells MG63 were co-cultured on the coatings. The results indicate that osteoblast viability and production of osteocalcin were promoted by the presence of ZnTCP. On the other hand, SrHA inhibited osteoclastogenesis and osteoclast differentiation, as demonstrated by the observed increase of the osteoprotegerin/RANKL ratio and decrease of the number of TRAP-positive multinucleated cells when increasing SrHA amount in the coatings. The results indicate that the possibility to tailor the composition of the coatings provides materials able to modulate bone growth and bone resorption.


Assuntos
Fosfatos de Cálcio/química , Hidroxiapatitas/química , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Estrôncio/química , Fosfatos de Cálcio/farmacologia , Linhagem Celular , Técnicas de Cocultura , Humanos , Hidroxiapatitas/farmacologia , Microscopia Eletrônica de Varredura , Osteoblastos/ultraestrutura , Osteoclastos/ultraestrutura , Espectrometria por Raios X , Estrôncio/farmacologia , Difração de Raios X , Zinco/química
12.
Eur J Pharm Biopharm ; 127: 120-129, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29454808

RESUMO

The development of new biomaterials able to favor bone formation and to inhibit bone abnormal resorption is mandatory to face the increasing number of age-related musculo-skeletal disorders. Moreover, the increasing antibiotic resistance of clinically important bacteria, which is among the main causes of implant failure, requires new antimicrobial systems. In this study, we prepared multifunctional materials consisting of hydroxyapatite-zoledronate composite crystals decorated with Ag Nanoparticles (AgNPs). Zoledronate, a potent bisphosphonate widely applied for the treatment of pathologies associated to abnormal bone loss, was incorporated into hydroxyapatite up to about 8 wt%. Loading of poly(ethylenimine) - stabilized AgNPs onto the crystals was promoted by zoledronate functionalization and provoked a significant variation of the values of zeta potential. The results of in vitro tests demonstrate that the multifunctional materials combine the beneficial actions of zoledronate and AgNPs. In fact, they improve osteoblast differentiation and activity, whereas they inhibit osteoclastogenesis and osteoclast differentiation, and significantly hinder the growth of multi-drug resistant Gram positive and Gram negative bacteria. As a consequence, they can be exploited both as antiresorptive agents and as antimicrobial materials able to prevent the development of bone-associated infections.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas/química , Osteoclastos/efeitos dos fármacos , Prata/química , Materiais Biocompatíveis/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Difosfonatos/química , Difosfonatos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Imidazóis/química , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana/métodos , Osteoblastos/efeitos dos fármacos , Ácido Zoledrônico
13.
J Funct Biomater ; 9(1)2018 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-29342839

RESUMO

Bisphosphonates (BPs) are the most utilized drugs for the treatment of osteoporosis, and are usefully employed also for other pathologies characterized by abnormally high bone resorption, including bone metastases. Due to the great affinity of these drugs for calcium ions, calcium phosphates are ideal delivery systems for local administration of BPs to bone, which is aimed to avoid/limit the undesirable side effects of their prolonged systemic use. Direct synthesis in aqueous medium and chemisorptions from solution are the two main routes proposed to synthesize BP functionalized calcium phosphates. The present review overviews the information acquired through the studies on the interaction between bisphosphonate molecules and calcium phosphates. Moreover, particular attention is addressed to some important recent achievements on the applications of BP functionalized calcium phosphates as biomaterials for bone substitution/repair.

14.
Colloids Surf B Biointerfaces ; 163: 73-82, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29278802

RESUMO

In this paper we developed an innovative, effective and rapid one-step approach to crosslink mucoadhesive gelatin films for buccal drug delivery. The method, which involves the application of non-equilibrium pressure plasma for 3 or 5 minutes/side, was compared with a classical approach based on the use of a chemical crosslinking agent, namely genipin. Econazole nitrate (ECN), an imidazole antifungal agent used for the treatment of skin infections and mucosal candidiasis, was selected as model drug. X-Ray Diffraction characterization performed on the drug-containing gelatin films revealed that ECN undergoes to a topotactic transformation into Econazole (EC) immediately after mixing with gelatin suggesting the occurrence of an acid-base reaction between drug and gelatin during film processing. Plasma treatment, as well as genipin crosslinking, did not provoke any further variation of EC structure. However, plasma exposure significantly improved films adhesiveness and allowed to reach mucoadhesive strength values more than double with respect to those obtained with genipin, ascribable to the presence of polar and hydrophilic groups on the plasma treated film's surface. A residence time of at least 48 h was obtained by properly selecting the plasma exposure times. These results, together with the in-vitro data showing retention of antifungal efficacy against a strain of Candida albicans, demonstrated that plasma treatment was a valid and rapid alternative, easy to scale-up, to chemical crosslinking methods for the production of highly mucoadhesive gelatin-based films.


Assuntos
Reagentes para Ligações Cruzadas/química , Portadores de Fármacos , Gelatina/química , Iridoides/química , Gases em Plasma/química , Adesividade , Administração Bucal , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Pressão Atmosférica , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Econazol/química , Econazol/farmacologia , Cinética , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Suínos , Resistência à Tração
15.
J Inorg Biochem ; 178: 43-53, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29049953

RESUMO

In this work we developed new antibacterial composite materials using polydopamine (PDA) to trigger the deposition of silver nanoparticles (AgNPs) onto calcium phosphates, namely octacalcium phosphate (OCP) and α-tricalcium phosphate (αTCP). Functionalization of OCP and αTCP with a self-polymerized polydopamine layer was obtained by soaking the calcium phosphates in dopamine solution. The PDA surface of functionalized calcium phosphates (OCPd and αTCPd) promoted the deposition of AgNPs by reducing silver ions when soaked in a silver nitrate solution. The amount of deposited AgNPs can be modulated by varying the concentration of silver nitrate solution and the type of substrate. The results of in vitro tests carried out with osteoblast-like MG63 cells indicate that the combination of AgNPs with OCP provides more biocompatible materials than those obtained using αTCP as substrate. In particular, the study of osteoblast activity and differentiation was focused on the samples OCPdAg5 (silver content=8.2wt%) and αTCPdAg5 (silver content=4.7wt%), which did not show any cytotoxicity, and compared with those obtained on pure OCP and αTCP. The results demonstrate that the AgNPs loaded materials support osteoblast viability and differentiation, whereas they significantly inhibit the growth of relevant antibiotic-resistant pathogenic bacteria.


Assuntos
Antibacterianos/síntese química , Biomimética , Fosfatos de Cálcio/química , Indóis/química , Polímeros/química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/química , Humanos , Nanopartículas/química , Osteoblastos/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Reação em Cadeia da Polimerase , Prata/química , Propriedades de Superfície
16.
J Biomed Mater Res A ; 106(4): 914-923, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29143449

RESUMO

The demand of new strategies for the induction of bone regeneration is continuously increasing. Biomimetic porous gelatin-nanocrystalline hydroxyapatite scaffolds with tailored properties were previously developed, showing a positive response in terms of cell adhesion, proliferation, and differentiation. In the present paper, we focused on their osteoinductive properties. The effect of scaffolds on osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was investigated in vitro. hMSCs were seeded on GEL (type A gelatin) and GEL containing 10 wt% hydroxyapatite (GEL-HA) and cultured in osteogenic medium. Results showed that GEL and GEL-HA10 sustained hMSC differentiation, with an increased ALP activity and a higher expression of bone specific genes. The osteoinductive ability of these scaffolds was then studied in vivo in a heterotopic bone formation model in nude mice. The influence of hMSCs within the implants was examined as well. Both GEL and GEL-HA10 scaffolds mineralized when implanted without hMSCs. On the contrary, the presence of hMSC abolished or reduced mineralization of GEL and GEL-HA10 scaffolds. However, we could observe a species-specific response to the presence of HA, which stimulated osteogenic differentiation of human cells only. In conclusion, the scaffolds showed promising osteoinductive properties and may be suitable for use in confined critical defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 914-923, 2018.


Assuntos
Durapatita/farmacologia , Gelatina/farmacologia , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Osseointegração , Animais , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Coristoma/patologia , Reagentes para Ligações Cruzadas/química , Gelatina/ultraestrutura , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iridoides/química , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Nus , Nanoestruturas/ultraestrutura , Osseointegração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Microtomografia por Raio-X
17.
Eur J Pharm Biopharm ; 122: 6-16, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28986297

RESUMO

The aim of this work was to develop an innovative drug delivery system potentially useful for the local delivery of Bisphosphonates to bone tissue. We propose the use of Solid Lipid Microparticles (MPs), up to now mainly used for oral and topical drug delivery, as carrier for bisphosphonates due to the favourable biocompatibility and lower toxicity of the lipids compared with many polymers. The delivery platform consisted of a biomimetic α-tricalcium phosphate-gelatin cement (CPC) enriched with alendronate loaded MPs (MPs-AL) produced by the spray congealing technology. Alendronate direct addition to cement composition is limited since Alendronate is able to sequester calcium from calcium phosphates, thus preventing the setting of the cements. At variance, this approach permitted to load a relatively high amount of the drug on the CPC and allowed the controlled release of the highly water soluble alendronate. A Design of Experiment (DoE) was employed for the screening of the effects of the formulation variables related to the presence of unloaded microparticle (MPs) on the cement most important mechanical properties. Then, MPs loaded with 10% w/w of alendronate were produced using five different carriers (Stearic Acid, Stearilic Alcohol, Cutina HR, Tristearin and Precirol ATO5). All MPs-AL exhibited a spherical shape, encapsulation efficiency higher than 90% and prevalent particle size ranging from 100 to 150µm. Solid state characterization (DSC, HSM and X-ray powder diffraction) demonstrated that encapsulation of alendronate into MPs did not alter its crystal structure. MPs-AL addition to the cement provoked a modest lengthening of the setting times and of the hardening reaction leading to the complete transformation of α-tricalcium phosphate into calcium-deficient hydroxyapatite, without significantly affect the cement mechanical properties. Moreover, the results of in vitro AL release study performed on cements enriched with MPs-AL showed that the system allows a controlled release of the drug over time.


Assuntos
Cimentos para Ossos/química , Fosfatos de Cálcio/química , Difosfonatos/química , Lipídeos/química , Alendronato/química , Materiais Biocompatíveis/química , Química Farmacêutica/métodos , Preparações de Ação Retardada , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Teste de Materiais/métodos , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Polímeros/química , Difração de Raios X/métodos
18.
Colloids Surf B Biointerfaces ; 160: 493-499, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28992488

RESUMO

Bisphosphonates are widely employed drugs for the treatment of pathologies characterized by excessive bone resorption, and display a great affinity for apatitic supports. In this work we investigate how hydroxyapatite functionalization can influence the processes of adsorption and release of a bisphosphonate, namely risedronate. To this aim, pure hydroxyapatite (HA), hydroxyapatite with a partial substitution of Zn to Ca (ZnHA) and poly-ethylenimine-functionalized hydroxyapatite (HAPEI) were submitted to interaction with risedronate solution. The results indicate that the mechanisms of adsorption and release are greatly influenced by the type of the apatitic support. All the apatitic supports display Langmuir isotherms for risedronate adsorption. However in the case of HAPEI the plateau is not reached even at high equilibrium concentrations in solution. The data suggest that risedronate adsorption on HAPEI mineral-organic support occurs not only through chemisorption on apatitic phase, as on HA and ZnHA, but also through physisorption involved by PEI coating, which modulates also bisphosphonate release. These properties of tailor-made hydroxyapatite supports could be exploited to develop delivery systems for antiresorptive agents directly on osteoporotic sites.


Assuntos
Reabsorção Óssea/prevenção & controle , Osso e Ossos/efeitos dos fármacos , Durapatita/química , Polietilenoimina/química , Ácido Risedrônico/farmacologia , Adsorção , Animais , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/farmacocinética , Conservadores da Densidade Óssea/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Cinética , Microscopia Eletrônica de Transmissão , Ácido Risedrônico/química , Ácido Risedrônico/farmacocinética , Termodinâmica , Difração de Raios X
19.
J Biomed Mater Res A ; 105(12): 3293-3303, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28865182

RESUMO

In spite of its remarkable anti-oxidant, anti-inflammatory, anti-cancer properties and its possible inhibition activity towards bone resorption, quercetin therapeutic use is limited by its poor bioavailability. Herein we developed a new multifunctionalized system for the local administration of quercetin and alendronate, one of the most potent anti-osteoporotic drugs, with the aim to get a material with enhanced properties. To this purpose we loaded quercetin on hydroxyapatite functionalized with alendronate, as well as on hydroxyapatite. Characterization was performed by means of X-ray diffraction, FT-IR and Raman spectroscopies, thermogravimetric and spectrophotometric analyses. Loading of quercetin from hydro-alcoholic solution increased with time and reached a constant value of about 5 weight% on both substrates, without causing significant structural and morphological modifications. Quercetin functionalized materials exhibit relevant anti-oxidant properties, in agreement with their high radical scavenging activity, and a quercetin sustained release in phosphate buffer. In vitro osteoblast and osteoclast co-culture in a microenvironment altered by oxidative stress shows that both alendronate and quercetin significantly reduce osteoclast viability, whereas they are able to counteract the negative effect of oxidative stress on osteoblast viability and differentiation, suggesting that their relative amount in the functionalized materials can be utilized to tailor bone cells response. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3293-3303, 2017.


Assuntos
Alendronato/farmacologia , Antioxidantes/farmacologia , Conservadores da Densidade Óssea/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Alendronato/administração & dosagem , Antioxidantes/administração & dosagem , Materiais Biocompatíveis/química , Conservadores da Densidade Óssea/administração & dosagem , Linhagem Celular , Técnicas de Cocultura , Sistemas de Liberação de Medicamentos/métodos , Durapatita/química , Humanos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Quercetina/administração & dosagem , Difração de Raios X
20.
Sci Rep ; 7(1): 2712, 2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28578416

RESUMO

The development of biomaterials able to act against a wide range of bacteria, including antibiotic resistant bacteria, is of great importance since bacterial colonization is one of the main causes of implant failure. In this work, we explored the possibility to functionalize hydroxyapatite (HA) nanocrystals with some monocyclic N-thio-substituted ß-lactams. To this aim, a series of non-polar azetidinones have been synthesized and characterized. The amount of azetidinones loaded on HA could be properly controlled on changing the polarity of the loading solution and it can reach values up to 17 wt%. Data on cumulative release in aqueous solution show different trends which can be related to the lipophilicity of the molecules and can be modulated by suitable groups on the azetidinone. The examined ß-lactams-HA composites display good antibacterial activity against reference Gram-positive and Gram-negative bacteria. However, the results of citotoxicity and antibacterial tests indicate that HA loaded with 4-acetoxy-1-(methylthio)-azetidin-2-one displays the best performance. In fact, this material strongly inhibited the bacterial growth of both methicillin resistant and methicillin susceptible clinical isolates of S. aureus from surgical bone biopsies, showing to be a very good candidate as a new functional biomaterial with enhanced antibacterial activity.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Durapatita/química , Monobactamas/química , Monobactamas/farmacologia , Antibacterianos/síntese química , Azetidinas/química , Azetidinas/farmacologia , Bactérias/efeitos dos fármacos , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monobactamas/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA