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2.
Pan Afr Med J ; 39: 108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512844

RESUMO

Introduction: to evaluate the effect of dexamethasone biodegradable implant (DEX-I), on intraocular pressure (IOP), to determine the incidence of secondary ocular hypertension (OHT) and to analyze the IOP changes as per the treatment indication in Zambian cohort. Methods: retrospective consecutive case series of patients receiving one DEX-I between January 2016 and September 2018 with a minimum follow-up of four months in a tertiary care centre in Zambia. The IOP was recorded before the injection and at 1st week, 1st, 2nd, 3rd and 4th month after the injection. Ocular hypertension was defined as IOP ≥ 21 mmHg or an increase of ≥ 10 mmHg from baseline. Results: the effects of 122 injections given to ninety - nine patients (65 male: 65%; mean age 57.3) were included. The main indications for treatment were diabetic macular edema (DME, 52%), retinal vein occlusion (18%), post-surgical macular edema (18%) and non-infectious posterior uveitis (10%). Mean IOP before the injection was was 14.7mmHg and at 1st week, 1st, 2nd, 3rd and 4th months after the injection it was 14.4 (p=0.08), 16.1 (p=0.01), 17.5 (p<0.001), 15.7 (p=0.006) and 14.9 (p=0.06) mmHg, respectively. The incidence of secondary OHT was 30.32% in this cohort. Peak incidence of OHT was between 1 - 2 months, with majority of cases in DME group (75%) and 43% diabetic eyes followed by 23% non-infectious posterior uveitis cases developing OHT post injection. OHT was well managed with anti-glaucoma medications only. Conclusion: DEX-I showed a good pressure tolerance in this cohort. Secondary ocular hypertension developed in one-third of patients receiving injection which was transient and successfully managed with topical anti-glaucoma medications only. Diabetic eyes are more prone to develop ocular hypertension and therefore needs close monitoring following injection.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dexametasona/efeitos adversos , Implantes de Medicamento , Oftalmopatias/tratamento farmacológico , Oftalmopatias/fisiopatologia , Feminino , Seguimentos , Glucocorticoides/efeitos adversos , Humanos , Incidência , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/etiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem , Zâmbia
3.
Theriogenology ; 173: 73-82, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339906

RESUMO

Long-acting gonadotropin-releasing hormone (GnRH) analogs, which are approved for male dogs and ferrets, have been used off-label to suppress estrus in bitches predisposed to the side effects of spaying. Health data from the past 12 years were evaluated from bitches without progestogen pretreatment that received deslorelin acetate (DA) to suppress estrus for the first time before the age of 4.5 years. The study population included 32 client-owned bitches repeatedly treated with either 4.7 mg or 9.4 mg DA implants for a period of 5.3 ± 3.4 years (range 0.5-11.3 years). Follow-up information concerning immediate side effects of DA occurring within five months after the first DA treatment (n = 23) as well as long-term side effects of sustained gonadal suppression occurring after five months up to three years (n = 2), three years up to five years (n = 2) or more than five years (n = 8) were assessed through a questionnaire. Treatment was considered successful if no major side effects requiring medical treatment occurred, which applied to 26 out of 32 (81 %) bitches. In the six remaining bitches, the following major side effects led to treatment discontinuation: persistent urinary incontinence (n = 1), reoccurring induced heat (n = 1), uterine disease (n = 3) and/or ovarian tumor (n = 3). The bitches recovered completely after surgical spaying and/or DA implant removal. Minor side effects that did not require therapy or affect animal welfare included body weight changes (n = 18), subtle behavioral changes (n = 13), induced heat (n = 12), coat changes (n = 11), pseudocyesis (n = 6), transient urinary incontinence (n = 4), and/or temporary thickening of the uterine wall with little anechogenic content (n = 2). To examine a possible causal relationship between adverse side effects and DA treatment, further studies should compare the frequency of pathologies between groups of GnRH-treated, intact and spayed bitches of similar breeds and ages. Nevertheless, DA application before the age of 4.5 years may be a means of postponing surgical spaying for several years in breeds at high risk for developing urinary incontinence. Before DA is used in bitches, owners should be fully informed regarding possible side effects.


Assuntos
Estro , Furões , Animais , Cães , Implantes de Medicamento , Feminino , Masculino , Reprodução , Pamoato de Triptorrelina/análogos & derivados , Pamoato de Triptorrelina/farmacologia
4.
Eur J Pharm Sci ; 166: 105981, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34428483

RESUMO

PURPOSE: Dexamethasone (Dex) is a widely used drug for the treatment of inflammatory and autoimmune conditions, however, long-term systemic use of Dex is associated with serious adverse effects. The objective of the present study was to develop an implantable device to avoid side effects and realize a controlled release of Dex at the implant site. METHODS: Hydrophobic Dex was incorporated into biodegradable polyesters derived from PCL and Pluronic® L64 (PCL-Pluronic L64-PCL, PCLC) by hot-melt extrusion (HME) method to prepare Dex/PCLC implantable devices. Drug loading and encapsulation efficiency, a series of physicochemical properties, and in vivo features of the implants were studied. RESULTS: The maximum value of the drug loading and encapsulation efficiency for the Dex/PCLC implants were up to 47% and 94%, respectively. Incorporation of Dex resulted in accelerated crystallization of PCLC, decreased the wettability, increased contact angles and viscosity, and accelerated Dex release rate and degradation rate from the implants in vivo. Moreover, Dex/PCLC implants showed excellent biocompatibility. Furthermore, the inflammatory response to the Dex/PCLC implants was less severe than that to the positive control group. CONCLUSION: All these results suggested that Dex/PCLC implants might be a safe and controlled local drug delivery system with excellent inflammatory response suppression effect.


Assuntos
Implantes Absorvíveis , Tecnologia de Extrusão por Fusão a Quente , Cristalização , Dexametasona , Sistemas de Liberação de Medicamentos , Implantes de Medicamento , Poliésteres
5.
BMJ Case Rep ; 14(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244184

RESUMO

Ozurdex is a dexamethasone intravitreal implant used for the treatment of macular oedema. A rare but serious complication is the migration of the implant into the anterior chamber (AC) in eyes with absent or incomplete posterior capsules that may lead to corneal decompensation. We report the case of a 75-year-old woman who presented with a 1-day history of decreased vision in her left eye. She had a history of complicated cataract surgery and had received multiple Ozurdex implants for postoperative cystoid macular oedema in the same eye. She had significant left corneal decompensation and a mobile Ozurdex implant in the AC. We report a simple but novel surgical technique for removing an Ozurdex implant from the AC using an intravenous cannula (Venflon). This technique can also be applied to removing a fluocinolone acetonide (Iluvien) implant in similar situations.


Assuntos
Retinopatia Diabética , Edema Macular , Idoso , Câmara Anterior , Cânula , Dexametasona/efeitos adversos , Implantes de Medicamento , Feminino , Fluocinolona Acetonida/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico
6.
Middle East Afr J Ophthalmol ; 28(1): 18-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321818

RESUMO

PURPOSE: The purpose of this study was to evaluate the efficacy of the combination therapy of intravitreal aflibercept 2 mg (Eylea®) and a sustained-release dexamethasone 0.7 mg intravitreal implant (Ozurdex®) versus dexamethasone alone in providing better visual acuity in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: Seventy-four eyes of 74 patients with treatment-naïve ME secondary to RVO were included in this prospective nonrandomized case series and were studied over a 12-month follow-up period. Patients in the dexamethasone monotherapy group were treated with an initial Ozurdex® injection while patients in the combination therapy group were treated with an Eylea® injection followed 2 weeks later by an Ozurdex® injection. The treatment was repeated as needed. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure were evaluated periodically. The primary outcome measure was the BCVA. The secondary outcome measures included CMT, number of retreatments, and safety parameters. RESULTS: At 1 year, the primary endpoint was met. Patients receiving combined therapy had better mean visual acuity changes from baseline compared to those receiving monotherapy (0.369 ± 0.221 logarithm of the minimum angle of resolution [logMAR] vs. 0.218 ± 0.171 logMAR; P = 0.002). The secondary endpoints were not met since there were no significant differences in mean reductions in CMT (272.67 ± 82.35 vs. 248.11 ± 159.73; P = 0.412) and the mean number of retreatments was similar in the two groups (1.75 ± 1.13 vs. 1.42 ± 0.64; P = 0.126). CONCLUSION: Aflibercept with dexamethasone implants achieved better visual outcomes compared to dexamethasone monotherapy with no significant differences in intravitreal retreatment rates at the 1st year in eyes with ME secondary to RVO.


Assuntos
Inibidores da Angiogênese , Dexametasona , Edema Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Oclusão da Veia Retiniana , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Dexametasona/administração & dosagem , Implantes de Medicamento/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica
7.
Nat Commun ; 12(1): 4501, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301958

RESUMO

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.


Assuntos
Implantes de Medicamento/metabolismo , Infarto do Miocárdio/metabolismo , Nitratos/metabolismo , Óxidos de Nitrogênio/metabolismo , Animais , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Implantes de Medicamento/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Células RAW 264.7 , Ratos Sprague-Dawley , Taxa de Sobrevida , Suínos
8.
AAPS PharmSciTech ; 22(5): 174, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34114068

RESUMO

Posterior eye diseases are a common cause of vision problems in developing countries, which have encouraged the development of new treatment models for these degenerative diseases. Intraocular implants are one of the drug delivery systems to the posterior region of the eye. Using these implants, the blood-eye barrier can be bypassed; the complications caused by repeated in vitro administrations can be eliminated, and smaller amounts of the drug would be used during the treatment process. Meanwhile, biodegradable implants have received more attention due to their biodegradable structure and the lack of need for re-surgery to remove the rest of the system from the eye. The aim of this study is to employ biodegradable implants composed of polyethylene glycol (PEG) and 3-hydroxybutyrate-co-3-hydroxyvalerat (PHBV) to deliver betamethasone to the back of the eye in the treatment of retinopathy. PHBV polymer has been selected as the main polymer with a certain ratio of drug to polymer for fabrication of enamel and different amounts of PEG with three molecular weights used as pore generators to control drug release over a period of time. Based on the analysis of the results of differential scanning calorimetry (DSC) and FTIR spectroscopy, none of the polymers were degraded in the temperature range of the manufacturing process, and among betamethasone derivatives, the best option for implant preparation is the use of its basic form. Drug release studies over a period of three months showed that implants containing PHBV HV2% and PEG 6000 had a more appropriate release profile.


Assuntos
Implantes Absorvíveis , Betametasona/farmacocinética , Desenho de Fármacos , Poliésteres/farmacocinética , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacocinética , Betametasona/análogos & derivados , Betametasona/síntese química , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Implantes de Medicamento , Liberação Controlada de Fármacos , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacocinética
9.
J Zoo Wildl Med ; 52(2): 427-436, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130384

RESUMO

The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin®), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.


Assuntos
Animais de Zoológico , Anticoncepcionais/administração & dosagem , Pamoato de Triptorrelina/análogos & derivados , Animais , Aves , Coleta de Dados , Implantes de Medicamento , Feminino , Masculino , Mamíferos , América do Norte , Pamoato de Triptorrelina/administração & dosagem
10.
Diab Vasc Dis Res ; 18(3): 14791641211027324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190643

RESUMO

BACKGROUND: Insulin exerts vasculoprotective effects on endothelial cells (ECs) and growth-promoting effects on vascular smooth muscle cells (SMCs) in vitro, and suppresses neointimal growth in vivo. Here we determined the role of ECs and SMCs in the effect of insulin on neointimal growth. METHODS: Mice with transgene CreERT2 under the control of EC-specific Tie2 (Tie2-Cre) or SMC-specific smooth muscle myosin heavy chain promoter/enhancer (SMMHC-Cre) or littermate controls were crossbred with mice carrying a loxP-flanked insulin receptor (IR) gene. After CreERT2-loxP-mediated recombination was induced by tamoxifen injection, mice received insulin pellet or sham (control) implantation, and underwent femoral artery wire injury. Femoral arteries were collected for morphological analysis 28 days after wire injury. RESULTS: Tamoxifen-treated Tie2-Cre+ mice showed lower IR expression in ECs, but not in SMCs, than Tie2-Cre- mice. Insulin treatment reduced neointimal area after arterial injury in Tie2-Cre- mice, but had no effect in Tie2-Cre+ mice. Tamoxifen-treated SMMHC-Cre+ mice showed lower IR expression in SMCs, but not in ECs, than SMMHC-Cre- mice. Insulin treatment reduced neointimal area in SMMHC-Cre- mice, whereas unexpectedly, it failed to inhibit neointima formation in SMMHC-Cre+ mice. CONCLUSION: Insulin action in both ECs and SMCs is required for the "anti-restenotic" effect of insulin in vivo.


Assuntos
Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima , Receptor de Insulina/agonistas , Lesões do Sistema Vascular/tratamento farmacológico , Animais , Modelos Animais de Doenças , Implantes de Medicamento , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/lesões , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Masculino , Camundongos Knockout , Músculo Liso Vascular/lesões , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia
12.
Int J Pharm ; 606: 120622, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932539

RESUMO

Generally, an organic-solvent-based film is denser and tougher than a corresponding aqueous-dispersion-based film. However, Kollicoat® MAE100P films prepared from aqueous dispersions had greater tensile strengths compared to the films cast from organic solutions. It was proposed that MAE100P polymer particles in aqueous media had a core-shell structure with a hydrophilic shell and a hydrophobic core. The hydrophilic shell was rich in ionized methacrylic acid (MAA) groups and the hydrophobic core primarily contained unionized MAA and ethyl acrylate (EA). As a result, ionized MAA formed a continuous phase which worked as a rigid frame and greatly improved the mechanical properties of aqueous-dispersion-based films. In order to prove this theory and investigate the effect of ionization level on this polymer system, the properties of pH, turbidity, zeta potential, and particle size of MAE100P dispersions were measured as a function of ionization level. The tensile strengths and thermal and mechanical properties of MAE100P films prepared from organic solution or aqueous dispersions of different ionization levels were investigated as well. FTIR was used to characterize the polymer films. Drug release in 0.1 N HCl from coated pellets was studied using the basket method. The experimental results showed that the original MAE100P polymer particles (if not specified, the ionization level is 6%) had a highly-charged surface. The properties of polymer aqueous dispersions were significantly changed by the ionization levels. Aqueous-dispersion-based MAE100P films or coats were stronger and comparable to or somewhat more effective in inhibiting drug diffusion than were organic-solvent-based coats. The tensile strength initially increased and then decreased with an increase of ionization level, while the water-uptake rate by the films continuously increased. Two endothermic peaks were observed in the DSC thermograms for cured MAE100P films. The high-Tg endothermic peak increased with an increase in ionization level, while the low-Tg peak didn't exhibit significant change except for the 18% ionization film. In the dynamic mechanical analysis, two relaxations in the storage modulus were observed in the aqueous-dispersion-based films. These data may suggest a two-phase structure in the form of a core-shell structure. The tensile-strength ratio for aqueous-dispersion-based films over organic-solvent-based films for MAE100P was close to that reported for films formed from polymer substances/particles with core-shell structures. In summary, the core-shell structure might result in a two-phase structure in the bulk MAE100P film prepared from aqueous dispersion. This special structure led to significantly-improved mechanical properties for aqueous-dispersion-based MAE100 films. The ionization levels had complicated effects on the polymer system by increasing the amount of ionic aggregates while also solubilizing the polymer and changing the mechanism of film formation.


Assuntos
Polímeros , Implantes de Medicamento , Tamanho da Partícula , Solubilidade , Solventes
13.
Adv Ther ; 38(6): 3143-3153, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948926

RESUMO

PURPOSE: To evaluate morpho-functional outcomes of the intravitreal fluocinolone acetonide (FAc) implant. METHODS: Retrospective, observational, single-center study. Primary endpoint was the mean change in central macular thickness (CMT) from baseline to month 1-3. Secondary endpoints included mean CMT change from baseline to month 4-8 and 9-14 and mean best corrected visual acuity (BCVA), photopic negative response (PhNR) and b-wave of flash full-field electroretinogram (ERG) changes from baseline to month 1-3, 4-8, and 9-14. RESULTS: Fourteen patients (18 eyes) were included. Mean (standard deviation) CMT decreased from 473 (196) µm at baseline to 371 (163) µm at month 1-3 (mean difference - 102.3 ± 98.35 µm, 95% CI ± 46.4 µm; p < 0.0001) and this decrease tended to endure up to month 9-14. BCVA did not change significantly. There was an improvement in mean PhNR amplitude from 2.76 (1.65) µV at baseline to 3.73 (2.32) µV at month 1-3 (mean difference 0.91 (1.14) µV, 95% CI ± 0.54 µV, p = 0.003); b-wave amplitude improved from 8.83 (4.52) µV at baseline versus 10.05 (5.04) µV at month 1-3 (mean difference 1.22 (2.23) µV, 95% CI ± 1.08 µV, p = 0.0384). These ERG positive changes tended to endure up to month 9-14, although they did not reach statistical significance after month 3. CONCLUSIONS: Intravitreal FAc implant significantly improved anatomic as well as functional outcomes related to middle and inner retinal layers, known to be altered in diabetic retinopathy. Our findings support the hypothesis that intravitreal FAc implant may exert a protective effect in diabetic retinas with diabetic macular edema.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento , Fluocinolona Acetonida/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Estudos Retrospectivos , Acuidade Visual
14.
Nat Commun ; 12(1): 2875, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001908

RESUMO

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.


Assuntos
Corticosteroides/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Corticosteroides/química , Corticosteroides/farmacocinética , Animais , Células Cultivadas , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Dexametasona/química , Dexametasona/farmacocinética , Dimerização , Modelos Animais de Doenças , Implantes de Medicamento , Liberação Controlada de Fármacos , Polímeros/química , Coelhos , Ratos , Uveíte/metabolismo , Uveíte/prevenção & controle
15.
Tidsskr Nor Laegeforen ; 141(7)2021 05 04.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-33950659

RESUMO

BACKGROUND: Subcutaneous contraceptive implants are recommended to be placed in the medial upper arm. Here, the implant lies close to important neurovascular structures. CASE PRESENTATION: We have treated two women with ulnar nerve injuries after removal of such implants. Patient 1 sustained a near complete nerve injury. Despite nerve grafting and a distal nerve transfer, she had a poor outcome. Patient 2 had a partial injury and has made a reasonable recovery after neurolysis of the ulnar nerve that was entrapped in scar tissue. INTERPRETATION: Prognosis after peripheral nerve injuries in the upper arm in adults is poor, and as such these injuries are particularly serious. Any patient with an implant that is not readily palpable in the subcutaneous tissue should be referred to a hand surgeon who has training in exploring peripheral nerves. If emergent nerve injury is suspected, referral to a department of hand surgery is vital.


Assuntos
Anticoncepcionais Femininos , Implantes de Medicamento/efeitos adversos , Traumatismos dos Nervos Periféricos , Adulto , Braço , Anticoncepcionais Femininos/administração & dosagem , Feminino , Humanos , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/etiologia , Nervo Ulnar/cirurgia
16.
Expert Opin Pharmacother ; 22(13): 1761-1771, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33866902

RESUMO

Introduction: Testosterone deficiency (TD) is defined as low serum testosterone associated with symptoms and signs. There has been an increasing prevalence of TD in recent decades, especially in males aged 15-39. Many of these men will require long-term testosterone therapy (TT). Although the end-goals for all treatments are essentially the same, strategies for increasing serum testosterone should be decided individually.Areas covered: This review focuses on the pharmacological management of TD in adults which includes TT with different routes of administration, such as transdermal, buccal, intramuscular and subcutaneous injections, pellets, nasal gel, and oral (pills). The authors review the options for TT available in the USA with emphasis on newer therapies. Furthermore, they examine the efficacy of these therapies with comparison between potential advantages or disadvantages related to dosing, administration method, and adverse events.Expert opinion: Treating TD can be difficult due to the wide range of available medications, diverse side effects related to testosterone replacement and route-of-administration, and necessity for long-term therapy. The combination of pharmacological and non-pharmacological therapies can improve symptoms of TD and patient satisfaction. Each patient should be managed individually, and clinicians should consider available treatment regimens based on the route-of-administration, efficacy, safety, and cost based on a shared decision-making approach.


Assuntos
Hipogonadismo , Administração Cutânea , Adulto , Implantes de Medicamento/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Hipogonadismo/tratamento farmacológico , Masculino , Testosterona/uso terapêutico , Estados Unidos
17.
Nat Nanotechnol ; 16(7): 820-829, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33795849

RESUMO

The poor transport of molecular and nanoscale agents through the blood-brain barrier together with tumour heterogeneity contribute to the dismal prognosis in patients with glioblastoma multiforme. Here, a biodegradable implant (µMESH) is engineered in the form of a micrometre-sized poly(lactic-co-glycolic acid) mesh laid over a water-soluble poly(vinyl alcohol) layer. Upon poly(vinyl alcohol) dissolution, the flexible poly(lactic-co-glycolic acid) mesh conforms to the resected tumour cavity as docetaxel-loaded nanomedicines and diclofenac molecules are continuously and directly released into the adjacent tumour bed. In orthotopic brain cancer models, generated with a conventional, reference cell line and patient-derived cells, a single µMESH application, carrying 0.75 mg kg-1 of docetaxel and diclofenac, abrogates disease recurrence up to eight months after tumour resection, with no appreciable adverse effects. Without tumour resection, the µMESH increases the median overall survival (∼30 d) as compared with the one-time intracranial deposition of docetaxel-loaded nanomedicines (15 d) or 10 cycles of systemically administered temozolomide (12 d). The µMESH modular structure, for the independent coloading of different molecules and nanomedicines, together with its mechanical flexibility, can be exploited to treat a variety of cancers, realizing patient-specific dosing and interventions.


Assuntos
Implantes Absorvíveis , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular , Diclofenaco/farmacocinética , Diclofenaco/farmacologia , Docetaxel/farmacocinética , Docetaxel/farmacologia , Implantes de Medicamento/farmacocinética , Implantes de Medicamento/farmacologia , Feminino , Humanos , Camundongos , Camundongos Nus , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836613

RESUMO

Drug delivery systems featuring electrochemical actuation represent an emerging class of biomedical technology with programmable volume/flowrate capabilities for localized delivery. Recent work establishes applications in neuroscience experiments involving small animals in the context of pharmacological response. However, for programmable delivery, the available flowrate control and delivery time models fail to consider key variables of the drug delivery system--microfluidic resistance and membrane stiffness. Here we establish an analytical model that accounts for the missing variables and provides a scalable understanding of each variable influence in the physics of delivery process (i.e., maximum flowrate, delivery time). This analytical model accounts for the key parameters--initial environmental pressure, initial volume, microfluidic resistance, flexible membrane, current, and temperature--to control the delivery and bypasses numerical simulations allowing faster system optimization for different in vivo experiments. We show that the delivery process is controlled by three nondimensional parameters, and the volume/flowrate results from the proposed analytical model agree with the numerical results and experiments. These results have relevance to the many emerging applications of programmable delivery in clinical studies within the neuroscience and broader biomedical communities.


Assuntos
Sistemas de Liberação de Medicamentos , Modelos Químicos , Sistemas de Liberação de Medicamentos/instrumentação , Implantes de Medicamento , Eletroquímica , Desenho de Equipamento , Membranas Artificiais , Microfluídica/instrumentação , Reprodutibilidade dos Testes
19.
Brasília; CONITEC; abr. 2021.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1254316

RESUMO

CONTEXTO: A gravidez não intencional se caracteriza como um problema de saúde pública e abrange de forma ampla a gravidez não planejada e a gravidez não desejada. A taxa global de gravidez não intencional tem apresentado declínio nos últimos anos em todo o mundo. No Brasil, estima-se que mais da metade das gravidezes podem ser consideradas como não planejadas. A contracepção é a prevenção intencional da gravidez e é capaz de reduzir a mortalidade materna e neonatal. Contudo, muitas mulheres que desejam evitar a gravidez não utilizam contraceptivos, usam de forma inconsistente ou incorreto. O aconselhamento sobre os métodos contraceptivos e a educação sexual são estratégias que auxiliam a evitar a gravidez não intencional. O SUS disponibiliza uma variedade de métodos contraceptivos, reversíveis ou permanentes, além de ações e políticas voltadas para a saúde sexual e o planejamento familiar. TECNOLOGIA: Implante contraceptivo subdérmico de etonogestrel (IMPLANON NXT®). PERGUNTA: O uso do implante subdérmico de etonogestrel por mulheres adultas em idade reprodutiva é eficaz na prevenção de gravidez não planejada, custo-efetivo, e apresenta maior adesão ou satisfação comparadas aos contraceptivos oferecidos pelo SUS? EVIDÊNCIAS CLÍNICAS: O conjunto da evidência clínica de eficácia, adesão e segurança do implante subdérmico de etonogestrel para mulheres adultas em idade reprodutiva, maiores de 18 anos, é proveniente de três ensaios clínicos e cinco estudos de coorte, que foram avaliados como de baixa a moderada qualidade metodológica. O implante subdérmico de etonogestrel demonstrou maior eficácia contraceptiva e maior taxa de continuação de uso no decorrer de três anos frente ao DIU de cobre, embora as suas taxas de eficácia e continuação de uso também sejam elevadas. Ao final de um ano, o implante de etonogestrel demonstrou maior taxa de satisfação do que o DIU de cobre, embora a sua taxa de satisfação também seja elevada. De um modo geral, alterações no peso corporal e no índice de massa corporal foram maiores entre as usuárias do implante de etonogestrel e do injetável trimestral de acetato de medroxiprogesterona quando comparado ao DIU de cobre, embora para alguns autores estes achados não possuem significância clínica. O distúrbio do sangramento está entre as principais causas para a descontinuação de uso do implante subdérmico de etonogestrel, seguido por ganho de peso, e a expulsão do dispositivo e o distúrbio do sangramento estão entre as principais causas para a descontinuação de uso do DIU de cobre. Não foram encontrados estudos que preenchessem os critérios de inclusão da pergunta de pesquisa e que comparassem o implante subdérmico de etonogestrel frente aos demais contraceptivos reversíveis disponíveis no SUS. AVALIAÇÃO ECONÔMICA: Análise de custo-efetividade, com horizonte temporal de três anos, na perspectiva do SUS, comparou o implante subdérmico de etonogestrel frente ao DIU de cobre, aos injetáveis mensal e trimestral, à pílula e à minipílula disponível no SUS. Frente ao DIU de cobre, o implante resultou em uma razão de custo-efetividade incremental (RCEI) de R$ 6.356,07 por gravidez não planejada. O implante de etonogestrel foi dominante frente aos demais contraceptivos disponíveis no SUS. Em suas análises de sensibilidade, os resultados se mantiveram e o custo do implante de etonogestrel se destacou entre as variáveis que mais impactam no modelo. Foram identificadas algumas incertezas nos parâmetros, que podem estar impactando consideravelmente nos resultados, desfavorecendo os comparadores. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Na perspectiva da população por demanda aferida, o demandante estimou um incremento de R$5.924.413 no primeiro ano, para uma população de 3.869.561, e uma economia de R$4.426.700 no quinto ano, para uma população de 3.911.195. Ao final de cinco anos, uma economia de R$ 6.780.627,00. Na perspectiva epidemiológica da população, foi estimado um incremento de R$40.890.518 no primeiro ano, para uma população de 26.707.854, e uma economia de R$30.553.251, para uma população de 26.995.213. Ao final de cinco anos, uma economia de R$ 46.800.143,00. Para se chegar a estes valores, o demandante contabilizou os gastos com os métodos contraceptivos e com a gravidez não planejada, e subtraiu os valores entre cenários sem e com o implante subdérmico, considerando uma possível incorporação. As incertezas descritas podem estar subestimando o impacto orçamentário incremental, favorecendo a intervenção. Em cenários alternativos, desconsiderando os gastos com gravidez não planejada, estes valores podem variar de R$ 183.017.788,83 a R$ 1.263.195.588,17 ao final de cinco anos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foi detectado um anel vaginal de etinilestradiol associado com segestrone, indicado para mulheres adultas e em idade reprodutiva. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 93ª Reunião Ordinária, realizada no dia 09 de dezembro de 2020, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação do implante subdérmico de etonogestrel para prevenção da gravidez não planejada por mulheres adultas em idade reprodutiva entre 18 e 49 anos no SUS. Considerou-se que as evidências são favoráveis ao implante de etonogestrel, mas que a ampla população proposta pelo demandante juntamente com o impacto orçamentário estimado dificultaria a incorporação desta tecnologia no SUS. ANÁLISE DE IMPACTO ORÇAMENTÁRIO DE ACORDO COM O SEGMENTO POPULACIONAL DELINEADO PELA SVS E PELA SAPS: A Secretaria de Vigilância em Saúde (SVS) e a Secretaria de Atenção Primária à Saúde (SAPS) propuseram, na 92ª Reunião da Conitec, delinear um segmento da população que mais se beneficiaria com a possível incorporação do implante subdérmico de etonogestrel. De acordo com o levantamento, esta população seria compreendida por: mulheres usuárias de drogas; mulheres em situação de rua; mulheres vivendo com HIV; mulheres em idade fértil e em uso de talidomida; mulheres privadas de liberdade; mulheres cis trabalhadoras do sexo e mulheres em idade fértil em tratamento com tuberculose e em uso de aminoglicosídeos. Desta forma, o quantitativo apresentado desta população foi de 356.381 indivíduos. Desconsiderando os custos da gravidez não planejada, o percentual de uso do implante subdérmico de etonogestrel no cenário base e atualizando os custos de alguns métodos contraceptivos, o novo cenário apresentou um incremento de R$ 1.747.690,30 no primeiro ano e de R$ 5.580.520,95 no quinto ano. Ao final de cinco anos, o impacto orçamentário incremental de uma possível incorporação do implante subdérmico de etonogestrel no SUS para o segmento populacional proposto foi de R$ 17.710.388,26. CONSULTA PÚBLICA: A consulta pública (CP) nº 01/2021 foi realizada entre os dias 12/01/2021 a 01/02/2021. Foram recebidas 191 contribuições, sendo 72 pelo formulário para contribuições técnico-científico e 119 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. De um modo geral, os participantes da CP discordaram da recomendação preliminar da Conitec. As contribuições versaram sobre a eficácia, a efetividade e a segurança do implante de etonogestrel, além dassuas altastaxas de continuação e satisfação das usuárias. O desejo de se ampliar os contraceptivos disponíveis no SUS e de favorecer o planejamento familiar também foi mencionado. Outro ponto muito destacado foi acerca do benefício do implante hormonal para um grupo mais vulnerável da população. A redução no número de gravidez não planejada também foi amplamente considerada nas participações, e os seus custos foram atribuídos de forma intercalada entre indivíduo, SUS e sociedade. Por fim, conclui-se que as contribuições recebidas na CP sobre o implante subdérmico de etonogestrel para prevenção da gravidez não planejada por mulheres adultas em idade reprodutiva, entre 18 e 49 anos, foram importantes e evidenciaram o desejo de que este método pudesse ser disponibilizado a um subgrupo mais vulnerável da população. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário presentes na 95ª Reunião Ordinária da Conitec, no dia 03 de março de 2021, deliberaram, por maioria simples, sem nenhuma declaração de conflito de interesses, recomendar a incorporação, condicionada à criação de programa específico, do implante subdérmico de etonogestrel na prevenção da gravidez não planejada por mulheres em idade fértil: em situação de rua; com HIV/AIDS e em uso de dolutegravir; em uso de talidomida; privadas de liberdade; cis trabalhadoras do sexo; e em tratamento de tuberculose, usando aminoglicosídeos. Considerou-se que as evidências são favoráveis ao implante de etonogestrel e que o segmento da população delineada pela SVS e pela SAPS seria a que mais se beneficiaria do implante subdérmico de etonogestrel. Foi assinado o Registro de Deliberação nº 594/2021. DECISÃO: Incorporar o implante subdérmico de etonogestrel, condicionada à criação de programa específico, na prevenção da gravidez não planejada para mulheres em idade fértil: em situação de rua; com HIV/AIDS em uso de dolutegravir; em uso de talidomida; privadas de liberdade; trabalhadoras do sexo; e em tratamento de tuberculose em uso de aminoglicosídeos, no âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria nº 13, publicada no Diário Oficial da União nº 74, seção 1, página 235, em 22 de abril de 2021.


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Desogestrel/administração & dosagem , Anticoncepção/métodos , Gravidez não Planejada , Planejamento Familiar , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Análise Custo-Benefício/economia , Implantes de Medicamento
20.
J Zoo Wildl Med ; 52(1): 300-305, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827189

RESUMO

Batrachochytrium dendrobatidis (Bd) is an important fungal pathogen present in wild hellbender (Cryptobranchus alleganiensis) populations that appears to cause disease during novel exposure and acute stress. Hellbender repatriation efforts are ongoing to combat declining populations, but mortality by chytridiomycosis (disease from Bd) after release has been reported. The goal was to determine whether a safe antifungal agent could be administered and provide prolonged plasma concentrations without repeated handling. A subcutaneous implant impregnated with 24.5 mg of terbinafine was tested in three juvenile eastern hellbenders (C. a. alleganiensis) raised in human care, and plasma terbinafine concentrations were recorded from weekly to biweekly for 141 days. Plasma concentrations were variable, with peak plasma concentrations of 1,610, 112, and 66 ng/ml between 28 and 56 days postimplant. Although all hellbenders achieved plasma concentrations above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml) at several time points, only one individual remained above this threshold for more than two consecutive time intervals. Results show the potential for these implants as a prophylaxis for chytridiomycosis in captive-to-wild hellbender releases. However, further investigation will be needed to determine the plasma concentrations required to achieve prophylaxis in vivo and implant reliability.


Assuntos
Antifúngicos/uso terapêutico , Batrachochytrium , Micoses/veterinária , Terbinafina/uso terapêutico , Urodelos , Animais , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Implantes de Medicamento , Micoses/prevenção & controle , Absorção Subcutânea , Terbinafina/administração & dosagem , Terbinafina/sangue
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