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1.
Adv Drug Deliv Rev ; 175: 113823, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34089777

RESUMO

Advancements in technology and material development in recent years has led to significant breakthroughs in the remit of fiber engineering. Conventional methods such as wet spinning, melt spinning, phase separation and template synthesis have been reported to develop fibrous structures for an array of applications. However, these methods have limitations with respect to processing conditions (e.g. high processing temperatures, shear stresses) and production (e.g. non-continuous fibers). The materials that can be processed using these methods are also limited, deterring their use in practical applications. Producing fibrous structures on a nanometer scale, in sync with the advancements in nanotechnology is another challenge met by these conventional methods. In this review we aim to present a brief overview of conventional methods of fiber fabrication and focus on the emerging fiber engineering techniques namely electrospinning, centrifugal spinning and pressurised gyration. This review will discuss the fundamental principles and factors governing each fabrication method and converge on the applications of the resulting spun fibers; specifically, in the drug delivery remit and in regenerative medicine.


Assuntos
Engenharia Biomédica/métodos , Sistemas de Liberação de Medicamentos/métodos , Ciência dos Materiais/métodos , Medicina de Precisão/métodos , Medicina Regenerativa/métodos , Centrifugação , Fenômenos Eletromagnéticos , Humanos , Pressão
2.
Eur J Pharm Biopharm ; 156: 20-39, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32871196

RESUMO

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices.


Assuntos
Microinjeções/instrumentação , Agulhas , Polímeros/química , Pesquisa Qualitativa , Tecnologia Farmacêutica/instrumentação , Liberação Controlada de Fármacos , Microinjeções/normas , Agulhas/normas , Poliésteres/química , Poliésteres/normas , Polímeros/normas , Povidona/química , Povidona/normas , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tecnologia Farmacêutica/normas
3.
Drug Discov Today ; 25(8): 1513-1520, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561300

RESUMO

Recently, remarkable efforts have focused on research towards enhancing and delivering efficacious and advanced therapeutic agents. Even though this involves significant challenges, innovative techniques and materials have been explored to overcome these. The advantageous properties of mesoporous silica nanoparticles (MSNs), such as unique morphologies and geometries, makes then favorable for use for various drug delivery targeting purposes, particularly in cancer therapy. As we discuss here, MSNs have been utilized over the past few decades to improve the efficiency of anticancer drugs by enhancing their solubility to render them suitable for application, reducing adverse effects, and improving their anticancer cytotoxic efficiency.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Dióxido de Silício/administração & dosagem , Animais , Humanos , Porosidade
4.
Drug Deliv Transl Res ; 8(6): 1815-1827, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29873037

RESUMO

Electrohydrodynamic atomization (EHDA) is an emerging technique for the production of micron and nano-scaled particles. The process often involves Taylor cone enablement, which results in a fine spray yielding formulated droplets, which then undergo drying during deposition. In this work, novel multi-tip emitter (MTE) devices were designed, engineered and utilized for potential up-scaled EHDA, by comparison with a conventional single-needle system. To demonstrate this, the active ketoprofen (KETO) was formulated using polyvinylpyrrolidone (PVP) polymer as the matrix material. Here, PVP polymer (5% w/v) solution was prepared using ethanol and distilled water (80:20) as the vehicle. KETO was incorporated as 5% w/w of PVP. Physical properties of resulting solutions (viscosity, electrical conductivity, density and surface tension) were obtained. Formulations were electrosprayed through both single and novel MTEs under EHDA conditions at various flow rates (5-300 µl/min) and applied voltages (0-30 kV). The atomization process using MTEs and single nozzle was monitored at using various process parameters via a digital optical camera. Resulting particles were collected 200 mm below processing heads and were analyzed using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Digital recordings confirmed stable MTE jetting at higher flow rates. Electron micrographs confirmed particle size variation arising due to nozzle head design and evidenced stable jetting derived greater near-uniform particles. DSC, XRD and TGA confirm KETO molecules were encapsulated and dispersed into PVP polymer particles. In conclusion, novel MTE devices enabled stable atomization even at higher flow rates when compared to conventional single-needle device. This indicates an exciting approach for scaling up (EHDA) in contrast to current efforts focusing on multiple-nozzle and pore-based processing outlets.


Assuntos
Composição de Medicamentos/métodos , Cetoprofeno/química , Povidona/química , Varredura Diferencial de Calorimetria , Microscopia Eletrônica de Varredura , Nanopartículas/química , Nebulizadores e Vaporizadores , Tamanho da Partícula , Propriedades de Superfície , Viscosidade
5.
Mol Pharm ; 14(6): 2010-2023, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28445052

RESUMO

Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems, and diagnostic agents. The handling and processing of such materials still constitutes a major challenge, which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent. Mode mapping of CO-ES led to an optimized atomization engineering window for stable jetting, leading to encapsulation of SPIONs within particles of diameter 0.65-1.2 µm and drug encapsulation efficiencies of around 92%. Electron microscopy was used to image the encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded particles (∼1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4) demonstrate a triphasic release profile. Further cell studies confirmed cell uptake and internalization at selected time points (t = 1, 2, and 4 h). The results suggest potential for using the CO-ES technique as an efficient way to encapsulate SPIONs together with sensitive drugs for the development of multimodal particles that have potential application for combined imaging and therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Sobrevivência Celular , Compostos Férricos/química , Genisteína/química , Células HeLa , Humanos , Microscopia de Força Atômica , Polímeros/química , Nanomedicina Teranóstica , Triglicerídeos/química
6.
Eur J Pharm Sci ; 102: 147-155, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28249823

RESUMO

In this study conventional electrospinning (ESp) was used to prepare a series of buccal films containing indomethacin (INDO, a nonsteroidal anti-inflammatory drug), Ethocel (10), hydroxypropylmethylcellulose (HPMC) and Tween® 80 at various concentrations. The films were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM), fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Drug release behaviour was assessed in vitro (buffer pH6.8). SEM revealed film morphology and mean fibre diameter was dependent on the process formulation. INDO was encapsulated in the amorphous state once electrospun as evidenced from DSC and XRD studies. The presence of other excipients within fibrous matrices was confirmed using FTIR and Raman spectroscopy. Loading and release of INDO from filamentous structures was influenced by formulation composition; indicating potential to 'fine-tune' dosage forms. Given that ESp is a one-step preparation method and operational at ambient conditions; an attractive route for engineering tailored film type dosage forms is presented. This is a valuable approach for optimizing dosage forms as needed in a single step for various age groups.


Assuntos
Anti-Inflamatórios não Esteroides/química , Celulose/análogos & derivados , Celulose/química , Sistemas de Liberação de Medicamentos , Indometacina/química , Administração Bucal , Anti-Inflamatórios não Esteroides/administração & dosagem , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Indometacina/administração & dosagem , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Polissorbatos/química , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Tensoativos/química , Tecnologia Farmacêutica , Difração de Raios X
7.
Drug Discov Today ; 22(1): 157-165, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27693432

RESUMO

Complex micro- and nano-structures enable crucial developments in the healthcare remit (e.g., pharmaceutical and biomaterial sciences). In recent times, several technologies have been developed and explored to address key healthcare challenges (e.g., advanced chemotherapy, biomedical diagnostics and tissue regeneration). Electrohydrodynamic atomization (EHDA) technologies are rapidly emerging as promising candidates to address these issues. The fundamental principle driving EHDA engineering relates to the action of an electric force (field) on flowing conducting medium (formulation) giving rise to a stable Taylor cone. Through careful optimization of process parameters, material properties and selection, nozzle and needle design, and collection substrate method, complex active micro- and nano-structures are engineered. This short review focuses on key selected recent and established advances in the field of pharmaceutical and biomaterial applications.


Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Técnicas Eletroquímicas/métodos , Nanotecnologia/métodos , Preparações Farmacêuticas/química , Tecnologia Farmacêutica/métodos , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Hidrodinâmica , Nanotecnologia/instrumentação , Propriedades de Superfície , Tecnologia Farmacêutica/instrumentação
8.
J Drug Target ; 24(7): 603-12, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26586147

RESUMO

Dexibuprofen (DXIBN) transdermal patches were formulated using various concentrations of selected polymeric excipients (matrix material; ethyl cellulose and polyvinylpyrrolidone, plasticizer (di-N-butyl phthalate), and a conventional permeation enhancer (almond oil)). Initial patch formulations were evaluated for their physiochemical properties (thickness, moisture uptake, final moisture content, and DXIBN content). Also, impact of patch components on resulting tensile strength and in vitro permeation were used to predict an optimal patch formulation using a quality-by-design (QbD) approach, which was subsequently evaluated and further compared with a commercial oral tablet dosage form for in vitro and in vivo release (rabbit model). Initially formulated patches demonstrated uniform thickness (0.44 ± 0.02 cm), relatively low moisture uptake (7.87 ± 1.11 w/w %), and highly acceptable drug loading values (100.0 ± 0.026%). The tensile strength of patches increased significantly with matrix polymer concentration and to a lesser degree with increase in plasticizer and permeation enhancer content, although these affected the permeation of DXIBN. Predicted properties (tensile strength and DXIBN steady-state flux) for the QbD-optimized formulation were in close agreement to experimental results. The QbD optimal patch formulation behavior differed significantly from the commercial tablet formulation in vivo. Such model-based predictions (QbD approach) will reduce cost and time in formulation development sciences.


Assuntos
Antirreumáticos/administração & dosagem , Portadores de Fármacos/química , Desenho de Fármacos , Ibuprofeno/análogos & derivados , Pele/metabolismo , Adesivo Transdérmico/normas , Animais , Antirreumáticos/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Ibuprofeno/administração & dosagem , Ibuprofeno/farmacocinética , Plastificantes/química , Polímeros/química , Coelhos , Pele/efeitos dos fármacos , Absorção Cutânea , Testes de Irritação da Pele , Solubilidade , Propriedades de Superfície , Resistência à Tração
9.
Pharmaceutics ; 7(4): 486-502, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26556364

RESUMO

Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

10.
J Mater Sci Mater Med ; 26(11): 256, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26449446

RESUMO

The viability of single and coaxial electrospray techniques to encapsulate model peptide-angiotensin II into near mono-dispersed spherical, nanocarriers comprising N-octyl-O-sulphate chitosan and tristearin, respectively, was explored. The stability of peptide under controlled electric fields (during particle generation) was evaluated. Resulting nanocarriers were analysed using dynamic light scattering and electron microscopy. Cell toxicity assays were used to determine optimal peptide loading concentration (~1 mg/ml). A trout model was used to assess particle behaviour in vivo. A processing limit of 20 kV was determined. A range of electrosprayed nanoparticles were formed (between 100 and 300 nm) and these demonstrated encapsulation efficiencies of ~92 ± 1.8%. For the single needle process, particles were in matrix form and for the coaxial format particles demonstrated a clear core-shell encapsulation of peptide. The outcomes of in vitro experiments demonstrated triphasic activity. This included an initial slow activity period, followed by a rapid and finally a conventional diffusive phase. This was in contrast to results from in vivo cardiovascular activity in the trout model. The results are indicative of the substantial potential for single/coaxial electrospray techniques. The results also clearly indicate the need to investigate both in vitro and in vivo models for emerging drug delivery systems.


Assuntos
Nanopartículas , Animais , Linhagem Celular , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Oncorhynchus mykiss , Tamanho da Partícula
11.
Curr Pharm Des ; 21(22): 3239-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26027562

RESUMO

Electrohydrodynamic atomization (EHDA) enabling platform technologies have gathered significant momentum over the last two decades. Utilisation of the underpinning jetting process in tandem with desired materials (including polymers, ceramics, metals and even naturally occurring compounds such as peptides, DNA and cells) provides the basis for novel engineered therapies. Through EHDA processes, the generation of a variety of nano-meter and micro-meter scaled structures with control on surface and encapsulation features is attainable in a single step. While a host of adaptable EHDA techniques have evolved (e.g. printing and template patterning), there are two main processes that continue to dominate: electrospraying (ESy) and electrospinning (ESp). Although ESp has drawn considerable researcher interest for nanofibre applications, ESy is an important and timely process for nano- and micro-particle fabrication. Thus, an appropriate evaluation of ESy is vital. This short review focuses on key developments in the ESy field in relation to nanotechnologies with potential healthcare applications using metals, polymers and ceramics. An insight into the process of particle formation (during EHDA spraying or ESy), process parameters and materials specifications, is provided. Emerging biomedical and other healthcare research through nanotechnologies are highlighted.


Assuntos
Nanotecnologia , Humanos , Metais/química , Nanomedicina/métodos , Nanopartículas/química , Nanotecnologia/métodos , Polímeros/química , Propriedades de Superfície
12.
Int J Pharm ; 473(1-2): 95-104, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24997411

RESUMO

A method in layering dressings with a superficial active layer of sub-micrometer scaled fibrous structures is demonstrated. For this, polyvinylpyrolidone (PVP)-indomethacin (INDO) fibres (5% w/v PVP, 5% w/w indomethacin, using a 50:50 ethanol-methanol solvent system) were produced at different flow rates (50 µL/min and 100 µL/min) via a modified electrospinning device head (applied voltage varied between 15 ± 2 kV). We further assessed these structures for their morphological, physical and chemical properties using SEM, AFM, DSC, XRD, FTIR and HPLC-UV. The average diameter of the resulting 3D (ca. 500 nm in height) PVP-INDO fibres produced at 50 µL/min flow rate was 2.58 ± 0.30 µm, while an almost two-fold increase in the diameter was observed (5.22 ± 0.83 µm) when the flow rate was doubled. However, both of these diameters were appreciably smaller than the existing dressing fibres (ca. 30 µm), which were visible even when layered with the active spun fibres. Indomethacin was incorporated in the amorphous state. The encapsulation efficiency was 75% w/w, with complete drug release in 45 min. The advantages are the ease of fabrication and deposition onto any existing normal or functionalised dressing (retaining the original fabric functionality), elimination of topical product issues (application, storage and transport), rapid release of active and controlled loading of drug content (fibre layer).


Assuntos
Anti-Inflamatórios não Esteroides/química , Bandagens , Sistemas de Liberação de Medicamentos , Indometacina/química , Povidona/química , Administração Cutânea , Anti-Inflamatórios não Esteroides/administração & dosagem , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Indometacina/administração & dosagem , Microscopia Eletrônica de Varredura , Povidona/administração & dosagem , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
13.
Acta Biomater ; 9(2): 5052-62, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23036949

RESUMO

Surface topography plays a crucial role in influencing cellular responses and has therefore been utilized in the development of numerous implantable devices. Whilst numerous studies have either investigated cell attachment or migration post-attachment, few have looked at the early-stages of this process temporally. The aim of this study was to evaluate the use of time-lapse microscopy to study the behaviour of fibroblasts cultured with polycaprolactone microfibres and to assess spatially and temporally the cell-structure interaction over a 24h period. Ordered polymeric structures were printed (predetermined) onto glass substrates using an electrohydrodynamic direct write process to produce fine (3-5 µm wide) structures. Fibroblast attachment and migration were characterized as a function of distance perpendicular from structures (∼17.3, 34.6 and 51.9 µm). The use of time-lapse microscopy revealed a gradual decrease in cell attachment as the distance from the microfibres was increased. The technique also revealed that some cells were attaching and detaching from the microfibre multiple times. Our findings demonstrate that time-lapse microscopy is a useful technique for evaluating early-stage cell-biomaterial interaction that is capable of recording important events that might otherwise be overlooked.


Assuntos
Técnicas de Cultura de Células/métodos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Poliésteres/farmacologia , Animais , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Sistemas Computacionais , Camundongos , Microscopia de Força Atômica , Soluções , Solventes , Fatores de Tempo , Imagem com Lapso de Tempo
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