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1.
Mol Pharm ; 19(1): 274-286, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34877863

RESUMO

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Géis , Pressão Intraocular/efeitos dos fármacos , Timolol/farmacologia , Administração Oftálmica , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Córnea/efeitos dos fármacos , Córnea/metabolismo , Géis/administração & dosagem , Poloxâmero , Álcool de Polivinil , Suínos , Timolol/administração & dosagem
2.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672949

RESUMO

Two different types of ordered mesoporous nanoparticles, namely MCM-41 and MCM-48, with similar pore sizes but different pore connectivity, were loaded with aprepitant via a passive diffusion method. The percentage of the loaded active agent, along with the encapsulation efficiency, was evaluated using High-performance Liquid Chromatography (HPLC) analysis complemented by Thermogravimetric Analysis (TGA). The determination of the pore properties of the mesoporous particles before and after the drug loading revealed the presence of confined aprepitant in the pore structure of the particles, while Powder X-ray Diffractometry(pXRD), Differential Scanning Calorimetry (DSC), and FTIR experiments indicated that the drug is in an amorphous state. The release profiles of the drug from the two different mesoporous materials were studied in various release media and revealed an aprepitant release up to 45% when sink conditions are applied. The cytocompatibility of the silica nanoparticles was assessed in Caco-2 cell monolayers, in the presence and absence of the active agent, suggesting that they can be used as carriers of aprepitant without presenting any toxicity in vitro.


Assuntos
Aprepitanto/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Administração Oral , Antieméticos/administração & dosagem , Antieméticos/farmacocinética , Aprepitanto/farmacocinética , Células CACO-2 , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Difusão , Liberação Controlada de Fármacos , Humanos , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porosidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
3.
AAPS PharmSciTech ; 22(1): 23, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400042

RESUMO

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.


Assuntos
Canabidiol/administração & dosagem , Canabinoides/administração & dosagem , Nanofibras/química , Administração Oral , Canabidiol/química , Canabinoides/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Ácidos Polimetacrílicos/química , Povidona/química
4.
Langmuir ; 36(44): 13292-13300, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33118809

RESUMO

Achieving strong adhesion in wet environments remains a technological challenge in biomedical applications demanding biocompatibility. Attention for adhesive motifs meeting such demands has largely been focused on marine organisms. However, bioadhesion to inorganic surfaces is also present in the human body, in the hard tissues of teeth and bones, and is mediated through serines (S). The specific amino acid sequence DpSpSEEKC has been previously suggested to be responsible for the strong binding abilities of the protein statherin to hydroxyapatite, where pS denotes phosphorylated serine. Notably, similar sequences are present in the non-collagenous bone protein osteopontin (OPN) and the mussel foot protein 5 (Mefp5). OPN has previously been shown to promote fracture toughness and physiological damage formation. Here, we investigated the adhesion strength of the motif D(pS)(pS)EEKC on substrates of hydroxyapatite, TiO2, and mica using atomic force microscopy (AFM) single-molecule force spectroscopy (SMFS). Specifically, we investigated the dependence of adhesion force on phosphorylation of serines by comparing findings with the unphosphorylated variant DSSEEKC. Our results show that high adhesion forces of over 1 nN on hydroxyapatite and on TiO2 are only present for the phosphorylated variant D(pS)(pS)EEKC. This warrants further exploitation of this motif or similar residues in technological applications. Further, the dependence of adhesion force on phosphorylation suggests that biological systems potentially employ an adhesion-by-demand mechanism via expression of enzymes that up- or down-regulate phosphorylation, to increase or decrease adhesion forces, respectively.

5.
Drug Dev Ind Pharm ; 46(8): 1253-1264, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32597338

RESUMO

OBJECTIVE: The inkjet printing (IP) and fused deposition modeling (FDM) technologies have emerged in the pharmaceutical field as novel and personalized formulation approaches. Specific manufacturing factors must be considered in each adopted methodology, i.e. the development of suitable substrates for IP and the incorporation of highly thermostable active pharmaceutical compounds (APIs) for FDM. In this study, IP and FDM printing technologies were investigated for the fabrication of hydroxypropyl methylcellulose-based mucoadhesive films for the buccal delivery of a thermolabile model drug. Significance: This proof-of-concept approach was expected to provide an alternative formulation methodology for personalized mucoadhesive buccal films. METHODS: Mucoadhesive substrates were prepared by FDM and were subjected to sequential IP of an ibuprofen-loaded liquid ink. The interactions between these processes and the performance of the films were evaluated by various analytical and spectroscopic techniques, as well as by in vitro and ex vivo studies. RESULTS: The model drug was efficiently deposited by sequential IP passes onto the FDM-printed substrates. Significant variations were revealed on the morphological, physicochemical and mechanical properties of the prepared films, and linked to the number of IP passes. The mechanism of drug release, the mucoadhesion and the permeation of the drug through the buccal epithelium were evaluated, in view of the extent of ink deposition onto the buccal films, as well as the distribution of the API. CONCLUSIONS: The presented methodology provided a proof-of-concept formulation approach for the development of personalized mucoadhesive films.


Assuntos
Derivados da Hipromelose/química , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Impressão Tridimensional
6.
Pharm Dev Technol ; 25(4): 517-523, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31903821

RESUMO

To this day, the oral delivery of biomacromolecules remains a major developmentally-oriented challenge. A combinatorial approach was followed at this study, to formulate an efficient carrier for the in vitro delivery of a model macromolecule, fluorescein isothiocyanate-dextran 4 kDa (FD4). The model macromolecule was formulated in a self-assembling peptide hydrogel (ac-(RADA)4-CONH2), prior to deposition in a hydroxypropyl methylcellulose-phthalate (HPMCP)-based 3D-printed capsule. Loading of FD4 was investigated for potential alterations on the structural (AFM) and gelling properties of the peptide carrier. Thermal analysis and morphological properties of the 3D-printed capsules were assessed by TGA, DSC and microscopy studies. For the peptide hydrogel, similar release profiles of FD4 were recorded in simulated gastric fluid pH 1.2 and phosphate buffer saline pH 7.4, indicating the need for a structural barrier, to protect the peptide carrier from the acidic environment of the stomach. The pH responsive character of the HPMCP-based capsule was evidenced in the release profiles of FD4 in a sequence of release media, i.e. simulated gastric fluid pH 1.2, simulated intestinal fluid pH 6.8 and phosphate buffer saline pH 7.4. The results supported the combinatorial formulation approach as a promising system for the efficient oral delivery of biomacromolecules.


Assuntos
Preparações de Ação Retardada/química , Dextranos/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Corantes Fluorescentes/administração & dosagem , Metilcelulose/análogos & derivados , Peptídeos/química , Cápsulas/química , Liberação Controlada de Fármacos , Fluoresceína-5-Isotiocianato/administração & dosagem , Hidrogéis/química , Concentração de Íons de Hidrogênio , Metilcelulose/química , Impressão Tridimensional
7.
Langmuir ; 34(11): 3438-3448, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29486562

RESUMO

Toward engineering approaches that are designed to optimize the particle size, morphology, and mucoadhesion behavior of the particulate component of inhaler formulations, this paper presents the preparation, physicochemical characterization, and preliminary in vitro evaluation of multicomponent polymer-lipid systems that are based on "spray-drying engineered" α-lactose monohydrate microparticles. The formulations combine an active (budesonide) with a lung surfactant (dipalmitoylphosphatidylcholine) and with materials that are known for their desirable effects on morphology (polyvinyl alcohol), aerosolization (l-leucine), and mucoadhesion (chitosan). The effect of the composition of formulations on the morphology, distribution, and in vitro mucoadhesion profiles is presented along with "Calu-3 cell monolayers" data that indicate good cytocompatibility and also with simulated-lung-fluid data that are consistent with the therapeutically useful release of budesonide.


Assuntos
Budesonida/química , Portadores de Fármacos/química , Excipientes/química , Lactose/química , Álcool de Polivinil/química , 1,2-Dipalmitoilfosfatidilcolina/química , 1,2-Dipalmitoilfosfatidilcolina/toxicidade , Administração por Inalação , Linhagem Celular Tumoral , Quitosana/química , Quitosana/toxicidade , Portadores de Fármacos/toxicidade , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes/toxicidade , Feminino , Humanos , Lactose/toxicidade , Leucina/química , Leucina/toxicidade , Masculino , Muco/química , Tamanho da Partícula , Álcool de Polivinil/toxicidade , Surfactantes Pulmonares/química , Surfactantes Pulmonares/toxicidade
8.
AAPS PharmSciTech ; 19(8): 3362-3375, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29948989

RESUMO

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (µCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.


Assuntos
Ácido Algínico/química , Fluoruracila/química , Impressão Tridimensional , Ácido Algínico/farmacocinética , Varredura Diferencial de Calorimetria/métodos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes/química , Excipientes/farmacocinética , Fluoruracila/farmacocinética , Concentração de Íons de Hidrogênio , Comprimidos/química , Tecnologia Farmacêutica/métodos , Difração de Raios X/métodos
9.
Langmuir ; 30(41): 12337-44, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25247739

RESUMO

Toward the development of microparticulate carriers for nasal administration, N-trimethylchitosan chloride (TMC) of low molecular weight (LMW) and high molecular weight (HMW) and low degree of quaternization (16% and 27%, respectively) was co-formulated into microparticles comprising of dipalmatoylphosphatidylcholine (DPPC) and poly(lactic-co-glycolic) acid (PLGA) via the spray-drying technique. The chitosan derivatives were characterized by means of nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and Fourier transfrom infrared (FTIR) spectroscopy. The size and morphology of the produced microparticles were assessed by scanning electron microscopy (SEM), whereas their mucoadhesive properties were investigated by means of atomic force microscopy-force spectroscopy (AFM-FS). The results showed that microparticles exhibit mucoadhesion when TMC is present on their surface above a threshold of TMC (>0.3% w/w).


Assuntos
Quitosana/química , Portadores de Fármacos/química , Microesferas , Administração Intranasal , Quitosana/administração & dosagem , Quitosana/síntese química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Eletrólitos/química , Microscopia de Força Atômica , Peso Molecular , Tamanho da Partícula , Polímeros/química , Propriedades de Superfície
10.
Nanomedicine ; 10(1): 197-205, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23916887

RESUMO

Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. FROM THE CLINICAL EDITOR: This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.


Assuntos
Fluoruracila/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Zeolitas/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Difusão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Fluoruracila/química , Humanos , Cinética , Simulação de Dinâmica Molecular , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Zeolitas/química
11.
Eur J Pharm Biopharm ; 197: 114212, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342421

RESUMO

Capsaicin (CAP) has been implicated as a gastroprotective agent in the treatment of peptic ulcers. However, its oral administration is hampered by its poor aqueous solubility and caustic effect at high administered doses. To address these limitations, we describe the development of gastric floating, sustained release electrospun films loaded with CAP. The nanofiber films were formulated using the polymers Eudragit RL/RS and sodium bicarbonate (SB) as the effervescent agent. The films were tested for their physicochemical properties, and film buoyancy and in vitro release of CAP were assessed in simulated gastric fluid. The cytocompatibility and anti-inflammatory properties of the films were evaluated in lipopolysaccharide (LPS)-stimulated Caco-2 cells. The amorphous films showed improved wettability, a short floating lag time (<1 s) and a total floating time of over 24 h accompanied by sustained CAP release for up to 24 h. CAP-loaded films demonstrated biocompatibility with Caco-2 cells and potential cytoprotective effects by attenuating inflammatory cytokine and reactive oxygen species (ROS) production in LPS-stimulated Caco-2 cells. The gastric floating electrospun films could serve as a platform for sustained and stomach-specific drug delivery applications.


Assuntos
Capsaicina , Lipopolissacarídeos , Humanos , Preparações de Ação Retardada/química , Células CACO-2 , Sistemas de Liberação de Medicamentos , Solubilidade , Comprimidos
12.
Int J Pharm ; 655: 124058, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38552754

RESUMO

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API's (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the "cheerios effect" that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API's of the formulation and the resemblance of their PK behavior with previously reported data.


Assuntos
Anti-Hipertensivos , Diltiazem , Humanos , Idoso , Preparações de Ação Retardada/química , Comprimidos/química , Liberação Controlada de Fármacos , Hidroclorotiazida , Impressão Tridimensional , Tecnologia Farmacêutica/métodos
13.
Gels ; 9(12)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38131970

RESUMO

In this work, a sodium alginate-based copolymer grafted by thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains was used as gelator (Alg-g-PNIPAM) in combination with methylcellulose (MC). It was found that the mechanical properties of the resulting gel could be enhanced by the addition of MC and calcium ions (Ca2+). The proposed network is formed via a dual crosslinking mechanism including ionic interactions among Ca2+ and carboxyl groups and secondary hydrophobic associations of PNIPAM chains. MC was found to further reinforce the dynamic moduli of the resulting gels (i.e., a storage modulus of ca. 1500 Pa at physiological body and post-printing temperature), rendering them suitable for 3D printing in biomedical applications. The polymer networks were stable and retained their printed fidelity with minimum erosion as low as 6% for up to seven days. Furthermore, adhered pre-osteoblastic cells on Alg-g-PNIPAM/MC printed scaffolds presented 80% viability compared to tissue culture polystyrene control, and more importantly, they promoted the osteogenic potential, as indicated by the increased alkaline phosphatase activity, calcium, and collagen production relative to the Alg-g-PNIPAM control scaffolds. Specifically, ALP activity and collagen secreted by cells were significantly enhanced in Alg-g-PNIPAM/MC scaffolds compared to the Alg-g-PNIPAM counterparts, demonstrating their potential in bone tissue engineering.

14.
J Pharm Sci ; 112(10): 2644-2654, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37549845

RESUMO

Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.


Assuntos
Deglutição , Omeprazol , Animais , Suínos , Sistemas de Liberação de Medicamentos , Administração Oral , Alginatos , Administração Bucal , Mucosa Bucal
15.
Small ; 8(15): 2381-93, 2012 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-22549909

RESUMO

Hybrid magnetic drug nanocarriers are prepared via a self-assembly process of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (p(MAA-g-EGMA)) on growing iron oxide nanocrystallites. The nanocarriers successfully merge together bio-repellent properties, pronounced magnetic response, and high loading capacity for the potent anticancer drug doxorubicin (adriamicin), in a manner not observed before in such hybrid colloids. High magnetic responses are accomplished by engineering the size of the magnetic nanocrystallites (∼13.5 nm) following an aqueous single-ferrous precursor route, and through adjustment of the number of cores in each colloidal assembly. Complementing conventional magnetometry, the magnetic response of the nanocarriers is evaluated by magnetophoretic experiments providing insight into their internal organization and on their response to magnetic manipulation. The structural organization of the graft-copolymer, locked on the surface of the nanocrystallites, is further probed by small-angle neutron scattering on single-core colloids. Analysis showed that the MAA segments selectively populate the area around the magnetic nanocrystallites, while the poly(ethylene glycol)-grafted chains are arranged as protrusions, pointing towards the aqueous environment. These nanocarriers are screened at various pHs and in highly salted media by light scattering and electrokinetic measurements. According to the results, their stability is dramatically enhanced, as compared to uncoated nanocrystallites, owing to the presence of the external protective PEG canopy. The nanocarriers are also endowed with bio-repellent properties, as evidenced by stability assays using human blood plasma as the medium.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Magnetismo , Doxorrubicina/química , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Polietilenoglicóis/química , Termogravimetria
16.
Biomater Adv ; 133: 112723, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35474147

RESUMO

Periodontal disease is associated with chronic inflammation and destruction of the soft and hard tissues in the periodontium. Scaffolds that would enable cell attachment and proliferation while at the same time providing a local sustained anti-inflammatory action would be beneficial in restoring or reversing disease progression. In the current study, silk sericin, a natural protein derived from the silkworm cocoons, was electrospun with poly lactide-co-glycolic acid (PLGA) and ketoprofen, and the composite scaffolds were assessed for their physicochemical and mechanical properties, as well as their biocompatibility and in vitro anti-inflammatory action. The composite scaffolds showed an increase in their hydrophilicity and an exceptional reinforcement of their mechanical properties, compared to plain PLGA scaffolds, sustaining drug release for up to 15 days. Human gingival fibroblasts showed a favorable attachment and proliferation on the composite scaffolds as visualized with scanning electron and confocal microscopy. A significant downregulation of the pro-inflammatory markers MMP-9 and MMP-3 and an upregulation of the anti-inflammatory gene IL-10 was achieved for lipopolysaccharide-stimulated RAW 264.7 macrophages after cultivation on the composite scaffolds. The current study demonstrated that silk sericin-PLGA composite scaffolds have the potential to simultaneously accommodate cell attachment and proliferation and achieve a sustained anti-inflammatory action in the treatment of periodontal diseases.


Assuntos
Sericinas , Engenharia Tecidual , Animais , Anti-Inflamatórios/farmacologia , Glicolatos , Humanos , Ácido Láctico/química , Camundongos , Periodonto , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células RAW 264.7 , Sericinas/farmacologia , Alicerces Teciduais/química
17.
J Pharm Pharmacol ; 74(10): 1498-1506, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34468746

RESUMO

OBJECTIVES: The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-solid extrusion (SSE) 3D printing. METHODS: Corn starch was used for ink preparation using ISO as model drug. The inks were characterized physicochemically and their viscoelastic properties were assessed with rheological analysis. The morphology of the printed dosage forms was visualized with scanning electron microscopy and their textural properties were evaluated using texture analysis. Dose accuracy was verified before in-vitro swelling and dissolution studies in simulated gastric fluid (SGF). KEY FINDINGS: Starch inks were printed with good resolution and high drug dose accuracy. The printed dosage forms had a soft texture to ease administration in paediatric patients and a highly porous microstructure facilitating water penetration and ISO diffusion in SGF, resulting in almost total drug release within 45 min. CONCLUSIONS: The ease of preparation and fabrication combined with the cost-effectiveness of the starting materials constitutes SSE 3D printing of starch-based soft dosage forms a viable approach for paediatric-friendly formulations in low-resource settings.


Assuntos
Isoniazida , Tuberculose Latente , Criança , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes/química , Humanos , Lactente , Impressão Tridimensional , Amido , Comprimidos/química , Tecnologia Farmacêutica/métodos , Água
18.
J Pharm Sci ; 111(9): 2562-2570, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35469835

RESUMO

In an effort to combine a child-friendly dosage form for medication administration in hospitalized pediatric patients and a user-friendly automated process for its preparation by health-care providers, the current study proposes a method for drug administration with breakfast using semi-solid extrusion 3D printing. Cereal was used as the platform carrier of the hydrophobic ibuprofen and the hydrophilic paracetamol to develop the drug loaded cereal ink. Rheological analysis was performed to identify the cereal ink with optimum viscosity for extrusion printing. Drug distribution and crystallinity within the printed cereal were assessed with confocal Raman microscopy and thermal and X-ray diffraction analysis, respectively, indicating molecular dispersion of both drugs within the cereal. High cereal porosity was associated with a higher milk absorption capacity and a decrease in their flexural force upon immersion in milk. Dissolution studies were performed in biorelevant media under fasted and fed state conditions and in the presence of full-fat and low-fat milk showing dissolution enhancement of the poorly soluble ibuprofen in the presence of the higher fat content milk. Concealing drug administration under the auspice of this essential daily eating habit is expected to facilitate overcoming adherence barriers to medication intake by pediatric patients within a hospital setting.


Assuntos
Grão Comestível , Ibuprofeno , Desjejum , Criança , Formas de Dosagem , Liberação Controlada de Fármacos , Hospitais , Humanos , Preparações Farmacêuticas , Impressão Tridimensional
19.
Artigo em Inglês | MEDLINE | ID: mdl-35405570

RESUMO

Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy. A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution mobile phase was developed to evaluate the production quality of both formulations (assay and dissolution profiles in gastric and intestinal fluids). Method's validation was carried out providing good linearity (r ≥ 0.9995), precision (RSD < 1.53%), recovery (96.9% - 103.7%) and limits of detection (LODSLF = 12 ng/mL, LODHA = 15 ng/mL). Experimental design and Plackett-Burman methodology was constructed to study the robustness of the analysis. In all composite substrates, a freezing lipid precipitation approach was used as purification step. The method was optimized by applying Central Composite design mode. The in-vitro/ex-vivo permeability studies of both formulations were evaluated by a Liquid Chromatography-Electron Spray Ionization Mass Spectrometry (LC-ESI/MS) +/- mode. The analysis of sulfamethazine (internal standard, SLM, m/z 279), HA (m/z 449, [M + HCOO]-), SLF (m/z 399) and its active metabolite mesalazine (MSL, m/z 154) was performed using a C18 column and gradient elution. The validation of the method met the requirements of the International Council for Harmonization (ICH) (r ≥ 0.9997, RSD ≤ 4.62%, Recovery > 95%, LODSLF = 1.28 ng/mL, LODHA = 1.07 ng/mL, LODMSL = 3.16 ng/mL). Based on the results, important conclusions were drawn concerning the role of excipients and SLF metabolism.


Assuntos
Mesalamina , Sulfassalazina , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Hidrocortisona/análogos & derivados , Permeabilidade , Reprodutibilidade dos Testes , Supositórios , Comprimidos
20.
Gels ; 8(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36354613

RESUMO

Medium Chain Triglyceride (MCT) oil was successfully combined with Glyceryl Monostearate (GMS) and Glyceryl Monoolein (GMO) to form oleogels that were subsequently whipped to form stable oleofoams. The co-crystallization of GMS and GMO at a ratio of 20:1, 20:2.5, and 20:5 within MCT oil was studied through Differential Scanning Calorimetry (DSC), X-ray Diffraction analysis (XRD), rheological analysis, Fluorescence Recovery after Photobleaching (FRAP), Fourier Transform Infrared Spectroscopy (FTIR), and polarized microscopy. The addition of 5% GMO resulted in the production of more stable oleogels in terms of crystal structure and higher peak melting point, rendering this formulation suitable for pharmaceutical applications that are intended to be used internally and those that require stability at temperatures close to 40 °C. All formulations were whipped to form oleofoams that were evaluated for their storage stability for prolonged period at different temperatures. The results show that oleofoams containing 5% MGO retained their foam characteristics even after 3 months of storage under different temperature conditions.

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