RESUMO
Interventions in structural heart disease cover many catheter-based procedures for congenital and acquired conditions including valvular diseases, septal defects, arterial or venous obstructions, and fistulas. Among the available procedures, the most common are aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure. Antithrombotic therapy for transcatheter structural heart disease interventions aims to prevent thromboembolic events and reduce the risk of short-term and long-term complications. The specific approach to antithrombotic therapy depends on the type of intervention and individual patient factors. In this review, we synopsize contemporary evidence on antithrombotic therapies for structural heart disease interventions and highlight the importance of a personalized approach. These recommendations may evolve over time as new evidence emerges and clinical guidelines are updated. Therefore, it's crucial for healthcare professionals to stay updated on the most recent guidelines and individualize therapy based on patient-specific factors and procedural considerations.
RESUMO
Limitations associated with the use of linear biodegradable polyesters in the preparation of anticancer nano-based drug delivery systems (nanoDDS) have turned scientific attention to the utilization of branched-chain (co-)polymers. In this context, the present study evaluates the use of novel branched poly(ε-caprolactone) (PCL)-based copolymers of different architectures for the preparation of anticancer nanoparticle (NP)-based formulations, using paclitaxel (PTX) as a model drug. Specifically, three PCL-polyol branched polyesters, namely, a three-arm copolymer based on glycerol (PCL-GLY), a four-arm copolymer based on pentaerythritol (PCL-PE), and a five-arm copolymer based on xylitol (PCL-XYL), were synthesized via ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), intrinsic viscosity, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy and cytotoxicity. Then, PTX-loaded NPs were prepared by an oil-in-water emulsion. The size of the obtained NPs varied from 200 to 300 nm, while the drug was dispersed in crystalline form in all formulations. High encapsulation efficiency and high yields were obtained in all cases, while FTIR analysis showed no molecular drug polymer. Finally, in vitro drug release studies showed that the studied nanocarriers significantly enhanced the dissolution rate and extent of the drug.
Assuntos
Antineoplásicos , Nanopartículas , Polietilenoglicóis/química , Espectroscopia de Infravermelho com Transformada de Fourier , Poliésteres/química , Nanopartículas/química , Antineoplásicos/química , Paclitaxel/química , Portadores de Fármacos/químicaRESUMO
This work describes the synthesis of poly(butylene adipate) (PBAd), by melt polycondensation, poly(l-lactic acid) (PLLA), by ring opening polymerization, and the new block copolymer PLLA/PBAd in ratios 90/10, 95/5, 75/25 and 50/50. Due to the biocompatibility and low toxicity of neat PBAd and PLLA, these copolymers are suitable to be used in biomedical applications. The 1H and 13C nuclear magnetic resonance spectroscopy techniques were employed for structural characterization. The thermal transitions, with an emphasis on crystallization, were assessed by differential scanning calorimetry, supplemented by X-ray diffraction and polarized optical microscopy. Molecular mobility studies were conducted using two advanced techniques, broadband dielectric spectroscopy and thermally stimulated depolarization currents. The results from the structural techniques, in combination with each other, provided proof of the presence of PLLA and PBAd blocks and, moreover, the successful copolymer synthesis. The overall data showed that the different co-polymer compositions result directly in severe changes in the polymer crystal distribution and, indirectly, the formation of PBAd micro/nano domains surrounded by PLLA. Furthermore, it was demonstrated that both the continuity of the two polymers throughout the copolymer volume and the semicrystalline morphology can be tuned to a wide extent. The latter makes these systems quite promising envisaging biomedical applications, including the encapsulation of small molecules, e.g. drug solutions. The molecular mobility map was constructed for these systems for the first time, revealing the local (short scale) and segmental (larger nm scale) mobility of PBAd and PLLA, as well as intermediate behaviors of the copolymers.
Assuntos
Poliésteres , Polímeros , Butileno Glicóis , Ácido Láctico , Difração de Raios XRESUMO
Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.
Assuntos
Sistemas de Liberação de Medicamentos , Moxifloxacina/farmacologia , Nanopartículas/química , Engenharia Tecidual , Proliferação de Células/efeitos dos fármacos , Difusão Dinâmica da Luz , Humanos , Magnésio/química , Microscopia Eletrônica de Varredura , Moxifloxacina/química , Osteogênese/efeitos dos fármacos , Porosidade , Dióxido de Silício/química , Difração de Raios XRESUMO
In this work, we synthesized poly(ε-caprolactone) (PCL) and three copolyesters of different architectures based on three different alcohols, namely a three arm-copolymer based on 1% glycerol (PCL_Gly), a four arm-copolymer based on 1% pentaerythrytol (PCL_PE), and a linear block copolymer based on â¼50% methoxy-poly(ethylene glycol) (PCL_mPEG), all simultaneously with the ring opening polymerization (ROP) of PCL. Due to their biocompatibility and low toxicity, these systems are envisaged for use in drug delivery and tissue engineering applications. Due to the in situ ROP during the copolyesters synthesis, the molecular weight of PCL, Wm initially â¼62 kg mol-1, drops in the copolymers from â¼60k down to â¼5k. For the structure-properties investigation we employed differential scanning calorimetry (DSC and TMDSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier transform infra red (FTIR) spectroscopy, polarized optical microscopy (POM), broadband dielectric spectroscopy (BDS) and isothermal water sorption. DSC revealed that the crystalline fraction of PCL increases whereas the crystallization rate drops in the copolymers in the order PCL â¼ PCL_Gly > PCL_PE â« PCL_mPEG, which coincides with that of decreasing Wm. In PCL_mPEG the major amount of PCL (87%) was found to crystallize while the majority of mPEG (92%) was found amorphous exhibiting constrained amorphous mobility and severely slower/weaker crystallization as compared to neat mPEG. Segmental dynamics in BDS, in agreement with DSC, is similar and in general slow for the samples of star-like structure for Wm ≥ 30k arising from PCL, whereas it is severely faster and enhanced in strength for the linear PCL_mPEG (lower Wm) copolymer arising from mPEG. For the latter system, the data provide indications for the formation of complex structures consisting of many small PCL crystallites surrounded by amorphous mPEG segments with constrained dynamics and severely suppressed hydrophilicity. These effects cannot be easily assessed by conventional XRD and POM, confirming the power of the dielectric technique. The overall recordings indicated that the different polymer architecture results in severe changes in the semicrystalline morphology, which demonstrates the potential for tuning the final product performance (permeability, mechanical).
Assuntos
Espectroscopia Dielétrica , Poliésteres , Varredura Diferencial de Calorimetria , Cristalização , PolietilenoglicóisRESUMO
In a century when environmental pollution is a major issue, polymers issued from bio-based monomers have gained important interest, as they are expected to be environment-friendly, and biocompatible, with non-toxic degradation products. In parallel, hyperbranched polymers have emerged as an easily accessible alternative to dendrimers with numerous potential applications. Glycerol (Gly) is a natural, low-cost, trifunctional monomer, with a production expected to grow significantly, and thus an excellent candidate for the synthesis of hyperbranched polyesters for pharmaceutical and biomedical applications. In the present article, we review the synthesis, properties, and applications of glycerol polyesters of aliphatic dicarboxylic acids (from succinic to sebacic acids) as well as the copolymers of glycerol or hyperbranched polyglycerol with poly(lactic acid) and poly(ε-caprolactone). Emphasis was given to summarize the synthetic procedures (monomer molar ratio, used catalysts, temperatures, etc.,) and their effect on the molecular weight, solubility, and thermal and mechanical properties of the prepared hyperbranched polymers. Their applications in pharmaceutical technology as drug carries and in biomedical applications focusing on regenerative medicine are highlighted.
Assuntos
Materiais Biocompatíveis , Dendrímeros , Portadores de Fármacos , Glicerol , Poliésteres , Polímeros , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Dendrímeros/síntese química , Dendrímeros/química , Dendrímeros/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Glicerol/síntese química , Glicerol/química , Glicerol/uso terapêutico , Humanos , Poliésteres/síntese química , Poliésteres/química , Poliésteres/uso terapêutico , Polímeros/síntese química , Polímeros/química , Polímeros/uso terapêutico , Medicina RegenerativaRESUMO
The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and physicochemical properties were evaluated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and dynamic light scattering (DLS). Results showed that the prepared nanoparticles ranged from ~150 to ~500 nm and had a spherical or irregular shape. In the case of annatto and UF annatto, due to the formation of H-bonds, the sunscreen agents were amorphously dispersed within CS nanoparticles, while in the case of saffron and UF saffron, crystalline dispersion was observed. All encapsulated materials had good thermal stability as well as color stability. In a further step, sunscreen emulsions were prepared based on the formed CS-sunscreen nanoparticles and evaluated for their stability in terms of pH and viscosity, along with their ultraviolet (UV) radiation protection ability in terms of sun protection factor (SPF). All prepared emulsions showed low cytotoxicity and good storage stability for up to 90 days, while minimum sunscreen protection was observed with SPF values varying from 2.15 to 4.85.
Assuntos
Quitosana/química , Cosméticos/química , Emulsões/química , Nanopartículas/química , Protetores Solares/química , Bixaceae , Carotenoides , Crocus , Estabilidade de Medicamentos , Células Endoteliais , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/ultraestrutura , Tamanho da Partícula , Extratos Vegetais , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Viscosidade , Difração de Raios XAssuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Oclusão Coronária/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Adulto , Valva Aórtica/cirurgia , Aortografia , Bioprótese , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Insuficiência Cardíaca/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Imageamento por Ressonância Magnética , Reoperação , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Myocardial cysts represent a miscellaneous and infrequent spectrum of conditions, with each of them coming from a different etiological background. Congenital myocardial cysts, neoplasia, cysts of infectious origin (bacterial, viral, or parasitic), and cardiac pathologies that may fake cystic content are all encompassed in this group. Although most patients are asymptomatic, some may occasionally present with obstruction, valvular dysfunction, or heart failure. Even more uncommon is the coexistence of a myocardial cyst with other extracardiac locations causing extracardiac symptoms. In this direction, the coexistence of a myocardial and endocranial cyst is extremely rare and can cause symptomatology from the affected organs (e.g., seizures). Cardiac investigation in this context is mainly dependent on non-invasive diagnostic modalities, and laboratory procedures. In this case report, we present a 26-year-old Congolese male admitted with dyspnea and epileptic seizures. Echocardiography revealed left ventricular and both mitral and tricuspid valve dysfunction and the presence of two myocardial cysts, while brain computed tomography showed an additional frontal cystic lesion. A precise diagnostic workup with a combination of non-invasive imaging, laboratory results, and epidemiology data assisted the diagnosis and guided the most suitable therapeutic choice.
RESUMO
In terms of drug delivery, the attractive properties of poly(L-lactic acid) (PLA) and its aliphatic polyesters, poly(ethylene adipate) (PEAd) and poly(butylene adipate) (PBAd), render them ideal co-formulants for the preparation of modified-release pharmaceutical formulations. Furthermore, we have previously demonstrated that by adding a "softer" aliphatic polyester onto the macromolecular chain of PLA, i.e., PEAd or PBAd, resulting in the formation of the PLA's copolymers (PLA-co-PEAd and PLA-co-PBAd, in 95/5, 90/10, 75/25 and 50/50 weight ratios), the hydrolysis rate is also severely affected, leading to improved dissolution rates of the active pharmaceutical ingredients (API). In the present report, we communicate our findings on the in vitro modified release of the chronobiotic hormone melatonin (MLT), in aqueous media (pH 1.2 and 6.8), from poly(L-lactic acid) and the aforementioned copolymer matrix tablets, enriched with commonly used biopolymers, such as hydroxypropylmethylcellulose (HPMC K15), lactose monohydrate, and sodium alginate. It was found that, depending on the composition and the relevant content of these excipients in the matrix tablets, the release of MLT satisfied the sought targets for fast sleep onset and sleep maintenance. These findings constitute a useful background for pursuing relevant in vivo studies on melatonin in the future.
RESUMO
(1) Background: A proposed approach to promote periodontal tissue regeneration in cases of peri-implantitis is the local administration of growth factors at the implant site. Recombinant human bone morphogenetic protein-2 (rh-BMP-2) can effectively promote bone regeneration and osseointegration and the development of appropriate carriers for its delivery is of paramount importance. The aim of the present study was to develop SBA-15 mesoporous nanoparticles (MSNs) with varying porosity, evaluate their biocompatibility with human Periodontal Ligament Cells (hPDLCs) and to investigate their effectiveness as carriers of rh-BMP-2. (2) Methods: SBA-15 type mesoporous silicas were synthesized via sol-gel reaction. The calcined SBA-15 samples were characterized by N2 porosimetry, Fourier transform-infrared spectrometry (FTIR), Scanning (SEM) and Transmission Electron Microscopy (TEM). Rh-BMP-2 loading and release kinetics were evaluated by UV spectroscopy. (3) Results: MSNs presented hexagonally arranged, tubular pores of varying length and diameter. Slightly higher loading capacity was achieved for SBA-15 with large pores that presented good hemocompatibility. MTT assay revealed no cytotoxic effects for all the tested materials, while SBA-15 with large pores induced a significant upregulation of cell viability at day 5. (4) Conclusions: SBA-15 MSNs may prove a valuable delivery platform towards the effective release of bone-inducing proteins.
RESUMO
Cytotoxic potential of Ag(i) coordination compounds against cancer cells is widely recognized, but their frequently low water solubility and potential adverse interactions of Ag(i) ions in biological media require their incorporation into suitable platforms to ensure effective transport and delivery at target sites. Herein, we developed and evaluated the in vitro cytotoxic activity of a biodegradable copolymer-based nano-sized drug delivery system for three cytotoxically active and lipophillic Ag(i) compounds. In particular, polymer-based nanoparticles of the newly synthesized amphiphilic methoxy-poly(ethylene glycol)-poly(caprolactone) (mPEG-PCL) copolymer were prepared as carriers for [Ag(dmp2SH)(PPh3)2]NO3 (1), [Ag(dmp2SH)(xantphos)]NO3 (2) and [Ag(dmp2S)(xantphos)] (3) (dmP2SH = 4,6-dimethylpyrimidine-2-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) which exhibit high cytotoxicity against HeLa cancer cells, while they maintain low toxicity against HDFa normal cells. Taking advantage of the favorable donor-acceptor Lewis acid-base and electrostatic interactions between functional groups of 1-3 and mPEG-PCL copolymer, the formation of [X]@mPEG-PCL (X = 1,2,3) nanoparticles with nearly spherical shape was achieved. Satisfactory loading capacities and encapsulation efficiencies were obtained (13-15% and 80-88%, respectively). Differences in their mean size diameters were observed, revealing a dependence on the individual structural characteristics of the Ag(i) compounds. In vitro release profiles of the nanoparticles showed an initial burst stage, followed by a prolonged release stage extending over 15 days, with their release rates being determined by the mean size of the nanoparticles, as well as the type and crystallinity of the encapsulated Ag(i) compounds. In vitro cytotoxicity studies revealed an increased cytotoxic activity of compounds 1-3 after their encapsulation in mPEG-PCL copolymer against HeLa cells, with the actual concentrations of the loaded compounds responsible for the inhibition of cell viability being reduced by 8 times compared to the compounds in free form. Therefore, the current drug delivery system improves the pharmacokinetic properties of the three cytotoxic and biocompatible Ag(i) compounds, and may be beneficial for future in vivo anticancer treatment.
RESUMO
The sustained release of pharmaceutical substances remains the most convenient way of drug delivery. Hence, a great variety of reports can be traced in the open literature associated with drug delivery systems (DDS). Specifically, the use of microparticle systems has received special attention during the past two decades. Polymeric microparticles (MPs) are acknowledged as very prevalent carriers toward an enhanced bio-distribution and bioavailability of both hydrophilic and lipophilic drug substances. Poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and their copolymers are among the most frequently used biodegradable polymers for encapsulated drugs. This review describes the current state-of-the-art research in the study of poly(lactic acid)/poly(lactic-co-glycolic acid) microparticles and PLA-copolymers with other aliphatic acids as drug delivery devices for increasing the efficiency of drug delivery, enhancing the release profile, and drug targeting of active pharmaceutical ingredients (API). Potential advances in generics and the constant discovery of therapeutic peptides will hopefully promote the success of microsphere technology.
RESUMO
In the present study, the preparation of controlled-released leflunomide (LFD)-loaded skin patches was evaluated, utilizing the combination of chitosan (CS) nanoparticles (NPs) incorporated into suitable poly(l-lactic acid) (PLLA) or poly(lactic-co-glycolic acid) (PLGA) polyester matrices. Initially, LFD-loaded CS NPs of ~600 nm and a smooth surface were prepared, while strong inter-molecular interactions between the drug and the CS were unraveled. In the following step, the prepared LFD-loaded CS NPs were incorporated into PLLA or PLGA, and thin-film patches were prepared via spin-coating. Analysis of the prepared films showed that the incorporation of the drug-loaded CS NPs resulted in a significant increase in the drug's release rate and extent as compared to neat LFD-loaded polyester patches (i.e., prepared without the use of CS NPs). In-depth analysis of the prepared formulations showed that the amorphization of the drug within the matrix and the increased wetting properties of the prepared CS NPs were responsible for the improved thin-film patch characteristics.
RESUMO
The present study evaluates the use of newly synthesized poly(l-lactic acid)-co-poly(butylene adipate) (PLA/PBAd) block copolymers as microcarriers for the preparation of aripiprazole (ARI)-loaded long acting injectable (LAI) formulations. The effect of various PLA to PBAd ratios (95/5, 90/10, 75/25 and 50/50 w/w) on the enzymatic hydrolysis of the copolymers showed increasing erosion rates by increasing the PBAd content, while cytotoxicity studies revealed non-toxicity for all prepared biomaterials. SEM images showed the formation of well-shaped, spherical MPs with a smooth exterior surface and no particle's agglomeration, while DSC and pXRD data revealed that the presence of PBAd in the copolymers favors the amorphization of ARI. FTIR spectroscopy showed the formation of new ester bonds between the PLA and PBAd parts, while analysis of the MP formulations showed no molecular drug-polyester matrix interactions. In vitro dissolution studies suggested a highly tunable biphasic extended release, for up to 30 days, indicating the potential of the synthesized copolymers to act as promising LAI formulations, which will maintain a continuous therapeutic level for an extended time period. Lastly, several empirical and mechanistic models were also tested, with respect to their ability to fit the experimental release data.
RESUMO
Considering that the extensive biomedical, pharmaceutics, cosmetic and other industrial applications of biomaterials (BMs) is of great concern nowadays, regarding their environmental risk, the present study aimed to investigate the effects of four BMs, poly(ε-caprolactone) (PCL), poly(butylene succinate) (PBSu), chitosan (CS) and modified chitosan (succinic acid grafted chitosan) (CS-Suc) in the form of microplastics (particle sizes less than 1 mm) on biochemical parameters of snails Cornu aspersum hemocytes. Due to the absence of knowledge about the environmentally relevant concentrations of BMs, snails were initially treated through their food with a wide range of nominal concentrations of each BM to define the half maximal effective concentration (NRRT50), according to the destabilization degree of hemocytes' lysosomal membranes (by mean of neutral red retention time/NRRT assay). Thereafter, snails were treated with each BM, at concentrations lower than the estimated NRRT50 values in all cases, for periods up to 15 days. After the end of the exposure period, a battery of stress indices were measured in hemocytes of challenged snails. According to the results, all parameters tested in BMs-treated snails statistically differed from those measured in BMs-free snails, thus indicating the pro-oxidant potential of BMs, as well as their ability to affect animals' physiology. The most considerable effect in most cases seems to be caused by modified chitosan and PCL, while chitosan appears to be the least toxic. A common response mechanism of snails' blood cells against the 4 BMs used in the present study was shown. After exposure to each of the studied BMs a significant augmentation in protein carbonyls, MDA equivalents and DNA damage, while a significant reduction in NRRT values was determined in the snails hemocytes, in relation to the unexposed animals. From the biochemical parameters examined, MDA equivalents and DNA damage seem to be more susceptible than the other parameters studied, to respond to BMs effect, with MDA to react with more sensitivity to PCL and CS, while DNA damage to CS-Suc and PBSu. Our results could suggest the simultaneous use of the latter biomarkers in biomonitoring studies of terrestrial ecosystems against the specific BMs.
Assuntos
Materiais Biocompatíveis , Plásticos , Animais , Materiais Biocompatíveis/toxicidade , Biomarcadores , Ecossistema , Estresse OxidativoRESUMO
The aim of the present study was to prepare a leflunomide (LFD) sustained release transdermal delivery system for the treatment of psoriasis. In this context, LFD-loaded nanoparticles (NPs) based on either neat chitosan (CS) or CS modified with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM, a sulfobetaine zwitterionic compound) were initially prepared via ionotropic gelation and characterized in terms of in vitro dissolution, physicochemical, and antibacterial properties. Results showed that the use of the SDAEM-modified CS resulted in the formation of LFD-loaded NPs with improved wetting and solubilization properties, better in vitro dissolution profile characteristics (i.e., higher dissolution rate and extent), and improved (enhanced) antibacterial properties. The resultant LFD-loaded NPs were then embedded in suitable thin-film skin patches, prepared via spin-coating, utilizing two different biodegradable polyesters, namely methoxy polyethylene glycol-b-poly(L-lactide) (mPEG-b-PLA, at a ratio of 25/75 mPEG to PLA) and poly(lactic-co-glycolic acid) (PLGA at a ratio of 75/25 DL-lactide/glycolide copolymer). Results showed the formation of polymeric thin-films with no agglomeration (or trapped air) and uniform structure in all cases, while the LFD-loaded NPs were successfully embedded in the polymeric matrix. Analysis of the obtained in vitro dissolution profiles revealed a sustained release profile of the drug for up to approximately twelve days, while between the two proposed systems, the use of CS-SDAEM NPs (independently of the polyester type) was the most promising formulation approach.
RESUMO
The plasticizing effect of three low molecular weight oligomers of aliphatic poly(alkylene succinate) polyesters, namely poly(butylene succinate) (PBSu), poly(ethylene succinate) (PESu), and poly(propylene succinate) (PPSu), on partially hydrolyzed poly(vinyl alcohol) (PVA) used in melt-based pharmaceutical applications, was evaluated for the first time. Initially, the three aliphatic polyesters were prepared by the melt polycondensation process and characterized by differential scanning calorimetry (DSC), 1H NMR, intrinsic viscosity, and size exclusion chromatography (SEC). Subsequently, their effect on the thermophysical and physicochemical properties of PVA was thoroughly evaluated. According to the obtained results, PVA was completely miscible with all three polyesters, while PESu induced PVA's thermal degradation, with the phenomenon starting from ~220 °C, in contrast to PBSu and PPSu, where a thermal profile similar to PVA was observed. Furthermore, molecular interactions between PVA and the prepared poly(alkylene succinate) polyesters were revealed by DSC, ATR-FTIR, and molecular dynamics simulations. Finally, melt flow index (MFI) measurements showed that, in contrast to PBSu, the use of PESu or PPSu significantly improved PVA's melt flow properties. Hence, according to findings of the present work, only the use of low molecular weight PPSu is suitable in order to reduce processing temperature of PVA and improve its melt flow properties (plasticizing ability) without affecting its thermal decomposition.
RESUMO
In the present work, the porous metal-organic framework (MOF) Basolite®F300 (Fe-BTC) was tested as a potential drug-releasing depot to enhance the solubility of the anticancer drug paclitaxel (PTX) and to prepare controlled release formulations after its encapsulation in amphiphilic methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles. Investigation revealed that drug adsorption in Fe-BTC reached approximately 40%, a relatively high level, and also led to an overall drug amorphization as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The dissolution rate of PTX-loaded MOF was substantially enhanced achieving a complete (100%) release within four days, while the neat drug only reached a 13% maximum rate (3-4 days). This PTX-Fe-BTC nanocomposite was further encapsulated into a mPEG-PCL matrix, a typical aliphatic amphiphilic copolyester synthesized in our lab, whose biocompatibility was validated by in vitro cytotoxicity tests toward human umbilical vein endothelial cells (HUVEC). Encapsulation was performed according to the solid-in-oil-in-water emulsion/solvent evaporation technique, resulting in nanoparticles of about 143 nm, slightly larger of those prepared without the pre-adsorption of PTX on Fe-BTC (138 nm, respectively). Transmission electron microscopy (TEM) imaging revealed that spherical nanoparticles with embedded PTX-loaded Fe-BTC nanoparticles were indeed fabricated, with sizes ranging from 80 to 150 nm. Regions of the composite Fe-BTC-PTX system in the infrared (IR) spectrum are identified as signatures of the drug-MOF interaction. The dissolution profiles of all nanoparticles showed an initial burst release, attributed to the drug amount located at the nanoparticles surface or close to it, followed by a steadily and controlled release. This is corroborated by computational analysis that reveals that PTX attaches effectively to Fe-BTC building blocks, but its relatively large size limits diffusion through crystalline regions of Fe-BTC. The dissolution behaviour can be described through a bimodal diffusivity model. The nanoparticles studied could serve as potential chemotherapeutic candidates for PTX delivery.
RESUMO
The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles.