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1.
Mol Biol (Mosk) ; 53(5): 860-870, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661484

RESUMO

It is time to celebrate the 125th anniversary of the first successful attempt to develop and use a specific high-titer antitoxic serum for treating diphtheria, a deadly infectious disease. This was followed by major advances in passive immunotherapy 75 years ago (production of pooled human IgG for subcutaneous injection) and 50 years ago (widespread technology for producing immunoglobulin preparations for intravenous administration). More than 200 tons of pooled human IgG are produced per year worldwide. The preparation is used primarily for IgG substitution in patients with primary and secondary immunodeficiencies, as well as for an immunomodulating treatment of a growing number of autoimmune and inflammatory diseases. These preparations contain the pooled IgG antibody repertoire of a large population of healthy plasma donors. This repertoire includes antibodies that neutralize pathogens and their factors of virulence, anti-idiotypic antibodies, and antibodies to other foreign and own proteins, as well as to carbohydrate antigens. Naturally polyspecific antibodies that are present in all healthy individuals play an important role as a first-line defense against bacteria and viruses. After exposure to protein-modifying agents, some IgG molecules can acquire the ability to bind novel structurally unrelated antigens. This phenomenon is referred to as induced polyspecificity. The list of these protein-modifying molecules was shown to include low-pH buffers, free heme, pro-oxidative ferrous ions, reactive oxygen species, etc. Such modified antibody preparations may have a therapeutic potential, since their administration to animals with experimental sepsis or aseptic systemic response syndromes significantly improved survival rates, while the same dose of the native preparation had no effect. We also hypothesize that the aggressive protein-modifying molecules released in sites of inflammation and tissue damage could also modify the antigen-binding behavior of surface immunoglobulin B cell receptors and the structurally related T cell receptors. This "specificity editing" of both types of receptors may play a major role in the body's defense mechanisms.


Assuntos
Imunoglobulina G/imunologia , Imunoglobulina G/uso terapêutico , Preparações Farmacêuticas/administração & dosagem , Animais , História do Século XIX , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/história , Inflamação/tratamento farmacológico , Inflamação/imunologia , Preparações Farmacêuticas/história , Sepse/tratamento farmacológico , Sepse/imunologia
2.
Adv Exp Med Biol ; 1141: 407-466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571171

RESUMO

Blood-brain interfaces comprise the cerebral microvessel endothelium forming the blood-brain barrier (BBB) and the epithelium of the choroid plexuses forming the blood-cerebrospinal fluid barrier (BCSFB). Their main functions are to impede free diffusion between brain fluids and blood; to provide transport processes for essential nutrients, ions, and metabolic waste products; and to regulate the homeostasis of central nervous system (CNS), all of which are attributed to absent fenestrations, high expression of tight junction proteins at cell-cell contacts, and expression of multiple transporters, receptors, and enzymes. Existence of BBB is an important reason that systemic drug administration is not suitable for the treatment of CNS diseases. Some diseases, such epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and diabetes, alter BBB function via affecting tight junction proteins or altering expression and function of these transporters. This chapter will illustrate function of BBB, expression of transporters, as well as their alterations under disease status.


Assuntos
Barreira Hematoencefálica , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo
3.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

Purpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
4.
Chem Pharm Bull (Tokyo) ; 67(10): 1144-1151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582634

RESUMO

Definitive screening design (DSD) is a new class of small three-level experimental design that is attracting much attention as a technical tool of a quality by design (QbD) approach. The purpose of this study is to examine the usefulness of DSD for QbD through a pharmaceutical study on the preparation of ethenzamide-containing orally disintegrating tablet. Model tablets were prepared by directly compressing the mixture of the active pharmaceutical ingredient (API) and excipients. The five evaluated factors assigned to DSD were: the contents of API (X1) and lubricant (X2), and the compression force (X3) of the tableting process, the mixing time (X4), and the filling ratio of powder in the V-type mixer (X5). After tablet preparation, hardness and disintegration time were measured. The same experiments were performed by using the conventional design of experiments [i.e., L8 and L16 orthogonal array designs and central composite design (CCD)]. Results showed that DSD successfully clarified how various factors contribute to tablet properties. Moreover, the analysis result from DSD agreed well with those from the L8 and L16 experiments. In additional experiments, response surfaces for tablet properties were created by DSD. Compared with the response surfaces created by CCD, DSD could produce reliable response surfaces for its smaller number of experiments. We conclude that DSD is a powerful tool for implementing pharmaceutical studies including the QbD approach.


Assuntos
Desenho de Drogas , Preparações Farmacêuticas/química , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Propriedades de Superfície , Comprimidos/administração & dosagem , Comprimidos/química
5.
Life Sci ; 237: 116907, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606378

RESUMO

Treatment of majority of eye diseases involve the use of eye drops or eye ointments, which have major drawbacks of needing frequent administration, lower bioavailability and inability to cross the various eye barriers. This necessitates the use of novel delivery systems. Microneedles (MNs) as an alternate novel delivery system facilitate drug delivery to various ocular diseases with promising approaches in healthcare. Advances in pharmaceutical technology have made MNs provide localized, effective, less invasive and targeted drug delivery in the eye. The purpose of this review is to provide an insight to efficacious therapeutic applications the MNs can bring in various ocular diseases. Out of which, glaucoma, age-related macular degeneration, uveitis, retinal vascular occlusion and retinitis pigmentosa are majorly discussed. Among the various types of MNs; solid coated, hollow and dissolving polymeric MNs are specifically focused for their applications in ocular diseases. In addition, MNs shows improvement in the visual acuity and decreases the progression of the different ocular diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Oftalmopatias/tratamento farmacológico , Microinjeções/instrumentação , Microinjeções/métodos , Preparações Farmacêuticas/administração & dosagem , Administração Oftálmica , Animais , Humanos , Agulhas
6.
Expert Opin Drug Metab Toxicol ; 15(9): 751-765, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31512953

RESUMO

Introduction: Over the last decade, the spread of next-generation sequencing technology along with the rising cost in health management in national health systems has led to widespread use/abuse of pharmacogenetic tests (PGx) in the practice of many clinical disciplines. However, given their clinical significance, it is important to standardize these tests for having an interaction with the clinical analysis laboratory (CAL), in which a PGx service can meet these requirements. Areas covered: A diagnostic test must meet the criteria of reproducibility and validity for its utility in the clinical routine. This present review mainly describes the utility of introducing PGx tests in the CAL routine to produce correct results useful for setting up personalized drug treatments. Expert opinion: With a PGx service, CALs can provide the right tool to help clinicians to make better choices about different categories of drugs and their dosage and to manage the economic impact both in hospital-based settings and in National Health Services, throughout electronic health records. Advances in PGx also allow a new approach for pharmaceutical companies in order to improve drug development and clinical trials. As a result, CALs can achieve a powerful source of epidemiological, clinical, and research findings from PGx tests.


Assuntos
Desenvolvimento de Medicamentos/métodos , Farmacogenética/métodos , Testes Farmacogenômicos/métodos , Animais , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos/tendências , Indústria Farmacêutica/métodos , Indústria Farmacêutica/tendências , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Humanos , Preparações Farmacêuticas/administração & dosagem , Farmacogenética/tendências , Testes Farmacogenômicos/tendências , Medicina de Precisão , Reprodutibilidade dos Testes
7.
Expert Rev Clin Pharmacol ; 12(10): 921-930, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31544557

RESUMO

Introduction: In each section of the human gastrointestinal (GI) tract we may find bacteria that are adapted to local conditions and fulfill an important role in the proper functioning of the body. The gut microorganisms are crucial in human physiology in areas as diverse as the brain and the immune system functions. Therefore, there is a close relationship between the intestinal microbiota, its metabolic activity, and health of the host. Areas covered: In this review, we explore the host-microbiome interactions and characterize the role they may play in drug metabolism and toxicity. The study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. Expert opinion: Increasing unhealthy eating habits, stress, antibiotic therapy, unfavorable environmental factors, and genetic predisposition contribute to imbalances in the composition and function of the GI tract microbes and the initiation and progression of disease processes. Restoration of the balanced gut microbiota composition is possible by oral administration of probiotics.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Microbioma Gastrointestinal/fisiologia , Preparações Farmacêuticas/metabolismo , Administração Oral , Animais , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/microbiologia , Trato Gastrointestinal/microbiologia , Humanos , Preparações Farmacêuticas/administração & dosagem , Probióticos/administração & dosagem
8.
Pharm Res ; 36(10): 148, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414302

RESUMO

Medications have been used during space missions for more than half a century, yet our understanding of the effects of spaceflight on drug pharmacokinetics and pharmacodynamics is poor. The space environment induces time-dependent alterations in human physiology that include fluid shifts, cardiovascular deconditioning, bone and muscle density loss, and impaired immunity. This review presents the current knowledge on the physiological effects of spaceflight that can translate into altered drug disposition and activity and eventually to inadequate treatment. It describes findings from studies in astronauts along with mechanistic studies in animal models and in vitro systems. Future missions into deeper space and the emergence of commercial spaceflight will require a more detailed understanding of space pharmacology to optimize treatment in astronauts and space travelers.


Assuntos
Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Medicina Aeroespacial , Animais , Astronautas , Gravitação , Humanos , Farmacocinética , Voo Espacial , Ausência de Peso/efeitos adversos
9.
Expert Opin Drug Metab Toxicol ; 15(8): 633-658, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274340

RESUMO

Introduction: In quantitative modeling, the resolving of underpredictions and overpredictions of hepatic clearance (CLh) makes a top priority for pharmacokinetic modelers. Clearly, the 'protein-mediated hepatic uptake' is a violation of 'the free drug hypothesis', but the lack of its consideration in CLh-predictive approaches may be one of the reasons to explain the discrepancies between predicted and observed values. Areas covered: We first review the two 'albumin-facilitated hepatic uptake' models that were recently challenged to improve the in vitro-to-in vivo extrapolation (IVIVE) of CLh by reducing the underprediction bias, particularly in the absence of albumin (ALB) in vitro compared to the presence of ALB in vivo. Second, we identify three types of interactions related to the ALB-bound drug moiety (i.e., ALB-lipids, ALB-proteins, and ALB-ligand allosteric interactions) that may be behind the 'ALB-mediated hepatic uptake' mechanism(s) for highly bound drugs. Main keywords used in our search are IVIVE; albumin; allostery; protein-mediated uptake; hepatic clearance; polarized hepatocytes. Expert opinion: Understanding the implication of these interactions and the enzyme/transporter interplay for each drug would help selecting the appropriate IVIVE model. Therefore, we have proposed a tree of decision for guidance. The next step is to improve the 'ALB-facilitated hepatic uptake' models to cover the remaining uncertainties.


Assuntos
Albuminas/metabolismo , Hepatócitos/metabolismo , Modelos Biológicos , Transporte Biológico , Humanos , Lipídeos/química , Fígado/metabolismo , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Farmacocinética , Ligação Proteica , Proteínas/metabolismo
10.
Acta Pharm ; 69(2): 131-153, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259723

RESUMO

Core-shell nanofibers have grown in popularity over the last decade owing to their special features and their many applications in biomedicine. They can be produced by electrospinning of immiscible polymer blends or emulsions through a single nozzle or by electrospinning using a coaxial nozzle. Several of the electrospinning parameters allow great versatility for the compositions and diameters of core-shell nanofibers to be produced. Morphology of core-shell nanofibers can be investigated using transmission electron microscopy and, in some cases, scanning electron microscopy. Several studies have shown that core-shell nanofibers have some advantages over monolithic nanofibers, such as better drug, protein, gene or probiotic incorporation into the nanofibers, greater control over drug release, and maintenance of protein structure and activity during electrospinning. We herein review the production and characterization of core-shell nanofibers, the critical parameters that affect their development, and their advantages as delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Nanofibras , Preparações Farmacêuticas/administração & dosagem , Liberação Controlada de Fármacos , Emulsões , Humanos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Preparações Farmacêuticas/química , Polímeros/química
11.
Acta Pharm ; 69(2): 155-176, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259725

RESUMO

In recent years, there has been a tendency toward creating innovative, easy to use and patient-friendly drug delivery systems suitable for every consumer profile, which would ensure safety, stability and acceptability of a drug. One of the relatively novel and promising approaches is the manufacture of orodispersible films (ODFs), which is an upcoming area of interest in drug delivery. They are defined as polymer thin films that disintegrate in the oral cavity within seconds, without drinking water or chewing, and eliminate the risk of choking. Gaining special usefulness in therapies of children and the elderly, ODFs seem to fill the gap in the range of preparations available for these groups of patients. As no detailed monography of ODFs including testing methods and uniform requirements has been presented in any of the pharmacopoeias to date, the aim of this article is to give an overview of the applied testing methods, their modifications and innovative approaches related to ODF quality assessment.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Administração Oral , Idoso , Química Farmacêutica/métodos , Criança , Humanos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/normas , Polímeros/química
12.
Acta Pharm ; 69(2): 197-215, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259729

RESUMO

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Adesivo Transdérmico , Administração Cutânea , Desenho de Drogas , Desenvolvimento de Medicamentos , Humanos , Preparações Farmacêuticas/química
13.
Semin Ophthalmol ; 34(4): 218-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31146619

RESUMO

Clinical pharmacology training for clinicians typically focuses on a drug's Active Pharmaceutical Ingredient. However, pharmaceutical formulation, the process of optimizing manufacturing methods and excipients to make a final drug product, is a critical process in determining whether a potential drug can become a realistic, routinely used therapeutic agent. This review focuses on the formulation methods used in commonly prescribed retina drug products.


Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas/administração & dosagem , Doenças Retinianas/tratamento farmacológico , Humanos , Lipossomos/química , Nanopartículas/química , Fosfolipídeos/química
14.
AAPS PharmSciTech ; 20(6): 231, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236781

RESUMO

In spite of the major advantages that the liquisolid technology offers, particularly in tackling poor bioavailability of poorly water-soluble drugs (i.e., BCS Class II drugs), there are a few critical drawbacks. The inability of a high liquid load factor, poor flowability, poor compactibility, and an inability to produce a high dose dosage form of a reasonable size for swallowing are major hurdles, hampering this technology from being commercially feasible. An attempt was therefore made to overcome these drawbacks whilst maintaining the liquisolid inherent advantages. This resulted in the emerging next generation of oral dosage forms called the liqui-pellet. All formulations were incorporated into capsules as the final product. Solubility studies of naproxen were conducted in different liquid vehicles, namely polyethylene glycol 200, propylene glycol, Tween 80, Labrafil, Labrasol, and Kolliphor EL. The scanning electron microscopy studies indicated that the liquid vehicle tends to reduce the surface roughness of the pellet. X-ray powder diffraction (XRPD) indicated no significant differences in the crystalline structure or amorphous content between the physical mixture and the liqui-pellet formulation. This was due to the presence of a high concentration of amorphous Avicel in the formulation which overshadowed the crystalline structure of naproxen in the physical mixtures. Flowability and dissolution tests confirmed that this next-generation oral dosage form has excellent flowability, whilst maintaining the typical liquisolid enhanced drug release performance in comparison to its physical mixture counterpart. The liqui-pellet also had a high liquid load factor of 1, where ~ 29% of the total mass was the liquid vehicle. This shows that a high liquid load factor can be achieved in a liqui-pellet without compromising flowability. Overall, the results showed that the poor flowability of a liquisolid formulation could be overcomed with the liqui-pellet, which is believed to be a major advancement into the commercial feasibility of the liquisolid concept.


Assuntos
Formas de Dosagem , Preparações Farmacêuticas/administração & dosagem , Administração Oral , Disponibilidade Biológica , Difração de Pó , Solubilidade
15.
AAPS PharmSciTech ; 20(6): 235, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236849

RESUMO

Brazil has established a framework for provision of generic pharmaceuticals including for orally inhaled and nasal drug products (OINDP) to its populace. This includes the development of guidelines or "resolutions" and normative instructions describing the Brazilian medicines agency's (Anvisa) expectations for demonstrating OINDP therapeutic equivalence. The Anvisa regulatory framework for OINDP therapeutic equivalence, challenges, and comparisons with the US Food and Drug Administration and European Medicines Agency approaches are assessed and discussed.


Assuntos
Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/normas , Equivalência Terapêutica , Administração por Inalação , Administração Intranasal , Brasil , Órgãos Governamentais , Humanos , Estados Unidos
16.
Curr Med Chem ; 26(24): 4681-4696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203795

RESUMO

Phytochemicals represent an important class of bioactive compounds characterized by significant health benefits. Notwithstanding these important features, their potential therapeutic properties suffer from poor water solubility and membrane permeability limiting their approach to nutraceutical and pharmaceutical applications. Lipid nanoparticles are well known carrier systems endowed with high biodegradation and an extraordinary biocompatible chemical nature, successfully used as platform for advanced delivery of many active compounds, including the oral, topical and systemic routes. This article is aimed at reviewing the last ten years of studies about the application of lipid nanoparticles in active natural compounds reporting examples and advantages of these colloidal carrier systems.


Assuntos
Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Humanos , Nanomedicina , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade
17.
Ceska Slov Farm ; 68(1): 12-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163963

RESUMO

Transdermal Therapeutic Systems (TTS) improve patient compliance especially due to its simple application and long-term action with the need to exchange the system every 12 hours to several days. The advantages also include elimination of first-pass effect, avoidance of gastrointestinal adverse effects, stable drug levels in the blood and simple discontinuation of therapy by patch removing. However, most drugs do not have the appropriate physicochemical properties to achieve therapeutic levels by transdermal application, therefore only a limited amount of drugs administered by this route is available on the market. Microneedles (MI) by their painless application appear to increase drug permeation when applied transdermally. In this review work, various types of MI (solid, coated, hollow, matrix, hydrogel forming) their size, shape, grouping, but also materials and technologies used in MI production are described. Finally, the work is focused on current clinical trials in which MI have been tested. MI with their unique properties have potential to increase the range of transdermally administered drugs currently applied by another route of administration. MI can simply pave the way for transdermal delivery to poorly penetrating small molecules as well as large molecules such as vaccines, monoclonal antibodies, or siRNA.


Assuntos
Sistemas de Liberação de Medicamentos , Agulhas , Preparações Farmacêuticas/administração & dosagem , Administração Cutânea , Humanos
18.
Int J Mol Sci ; 20(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159216

RESUMO

The development of age-appropriate formulations should focus on dosage forms that can deliver variable yet accurate doses that are safe and acceptable to the child, are matched to his/her development and ability, and avoid medication errors. However, in the past decade, the medication needs of neonates have largely been neglected. The aim of this review is to expand on what differentiates the needs of preterm and term neonates from those of the older paediatric subsets, in terms of environment of care, ability to measure and administer the dose (from the perspective of the patient and carer, the routes of administration, the device and the product), neonatal biopharmaceutics and regulatory challenges. This review offers insight into those challenges posed by the formulation of medicinal products for neonatal patients in order to support the development of clinically relevant products.


Assuntos
Preparações Farmacêuticas/administração & dosagem , Medicina de Precisão , Fatores Etários , Química Farmacêutica , Vias de Administração de Medicamentos , Composição de Medicamentos , Estabilidade de Medicamentos , Humanos , Recém-Nascido , Preparações Farmacêuticas/química , Medicina de Precisão/métodos
19.
Molecules ; 24(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159343

RESUMO

In this work, with the drug oxytetracycline (OTC) released, cell cytotoxicity and antimicrobial studies of dual-responsive sodium alginate and N-Isopropylacrylamide hydrogels (SA/pNIPAAm) with enclosed OTC were investigated. The molecular OTC release was explored with different acid-base conditions and temperature conditions. In order to characterize cell cytotoxicity and antimicrobial efficacy, time-dependent OTC release analysis of different acid-base conditions was performed in SA/pNIPAAm hydrogels. OTC@SA/pNIPAAm hydrogels showed excellent time-dependent antimicrobial efficacy, in which the IC50 values were 50.11 µg mL-1, 34.27 µg mL-1, and 22.39 µg mL-1 among three consecutive days, respectively. Meanwhile, the human cells showed excellent viability at the IC50 dosage of OTC@SA/pNIPAAm (50.11 µg mL-1). OTC@SA/pNIPAAm performed in this study indicated that SA/pNIPAAm may serve as drug carriers for sustainable release at a specific concentration and for being employed as substrates for decreasing drug toxicity. Besides, pH-responsive and thermos-responsive SA/pNIPAAm may lead to the better selectivity of drug release in the ideal location or site. Finally, the results demonstrate that the designed, dual-responsive, biocompatible OTC@SA/pNIPAAm hydrogels showed excellent antimicrobial efficacy and may potentially be found to have enormous applicability in the field of pharmaceutics.


Assuntos
Alginatos/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Hidrogéis/química , Preparações Farmacêuticas/administração & dosagem , Anti-Infecciosos/administração & dosagem , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Preparações Farmacêuticas/química , Análise Espectral
20.
BMC Bioinformatics ; 20(Suppl 7): 199, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074377

RESUMO

BACKGROUND: Drug adverse events (AEs), or called adverse drug events (ADEs), are ranked one of the leading causes of mortality. The Ontology of Adverse Events (OAE) has been widely used for adverse event AE representation, standardization, and analysis. OAE-based ADE-specific ontologies, including ODNAE for drug-associated neuropathy-inducing AEs and OCVDAE for cardiovascular drug AEs, have also been developed and used. However, these ADE-specific ontologies do not consider the effects of other factors (e.g., age and drug-treated disease) on the outcomes of ADEs. With more ontological studies of ADEs, it is also critical to develop a general purpose ontology for representing ADEs for various types of drugs. RESULTS: Our survey of FDA drug package insert documents and other resources for 224 neuropathy-inducing drugs discovered that many drugs (e.g., sirolimus and linezolid) cause different AEs given patients' age or the diseases treated by the drugs. To logically represent the complex relations among drug, drug ingredient and mechanism of action, AE, age, disease, and other related factors, an ontology design pattern was developed and applied to generate a community-driven open-source Ontology of Drug Adverse Events (ODAE). The ODAE development follows the OBO Foundry ontology development principles (e.g., openness and collaboration). Built on a generalizable ODAE design pattern and extending the OAE and NDF-RT ontology, ODAE has represented various AEs associated with the over 200 neuropathy-inducing drugs given different age and disease conditions. ODAE is now deposited in the Ontobee for browsing and queries. As a demonstration of usage, a SPARQL query of the ODAE knowledge base was developed to identify all the drugs having the mechanisms of ion channel interactions, the diseases treated with the drugs, and AEs after the treatment in adult patients. AE-specific drug class effects were also explored using ODAE and SPARQL. CONCLUSION: ODAE provides a general representation of ADEs given different conditions and can be used for querying scientific questions. ODAE is also a robust knowledge base and platform for semantic and logic representation and study of ADEs of more drugs in the future.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Linezolida/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Preparações Farmacêuticas/administração & dosagem , Sirolimo/efeitos adversos , Software , Adulto , Fatores Etários , Antibacterianos/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Preparações Farmacêuticas/análise
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