RESUMO
AIM: Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. METHOD: Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. RESULT: Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited â¼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. In situ liposomal gels showed 1.5x higher blood concentration than the control formula. CONCLUSION: In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.
Assuntos
Administração Intranasal , Disponibilidade Biológica , Colchicina , Géis , Lipossomos , Tamanho da Partícula , Poloxâmero , Polietilenoglicóis , Animais , Coelhos , Poloxâmero/química , Colchicina/administração & dosagem , Colchicina/análogos & derivados , Colchicina/farmacocinética , Polietilenoglicóis/química , Temperatura , Humanos , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacosRESUMO
Loteprednol etabonate (LE) is a topical corticosteroid for the symptomatic management of ocular conditions, encompassing both allergic and infectious etiologies. Owing to the dynamic and static barriers of the eye, LE exhibits significantly low bioavailability, necessitating an increase in the frequency of drug administration. The objective of this study is to overcome the limitations by developing niosomal systems loaded with LE. Design of Experiments (DoE) approach was used for the development of optimal niosome formulation. The optimal formulation was characterized using DLS, FT-IR, and DSC analysis. In vitro and ex vivo release studies were performed to demonstrate drug release patterns. After that HET-CAM evaluation was conducted to determine safety profile. Then, in vivo studies were carried out to determine therapeutic activity of niosomes. Zeta potential (ZP), particle size, polydispersity index (PI), and encapsulation efficacy (EE) were -33.8 mV, 89.22 nm, 0.192, and 89.6%, respectively. Medicated niosomes had a broad distribution within rabbit eye tissues and was absorbed by the aqueous humor of the bovine eye for up to 6 h after treatment. Cumulative permeated drug in the bovine eye and rabbit eye were recorded 52.45% and 54.8%, respectively. No irritation or hemorrhagic situation was observed according to the results of HET-CAM study. Thus, novel LE-loaded niosomal formulations could be considered as a promising treatment option for the dry-eye-disease (DED) due to enhanced bioavailability and decreased side effects.
Assuntos
Preparações de Ação Retardada , Síndromes do Olho Seco , Lipossomos , Etabonato de Loteprednol , Animais , Coelhos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Etabonato de Loteprednol/administração & dosagem , Etabonato de Loteprednol/farmacocinética , Síndromes do Olho Seco/tratamento farmacológico , Bovinos , Liberação Controlada de Fármacos , Tamanho da Partícula , Modelos Animais de Doenças , Administração Oftálmica , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Olho/metabolismo , Olho/efeitos dos fármacos , Humor Aquoso/metabolismo , Química Farmacêutica/métodos , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinéticaRESUMO
The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.
Assuntos
Lipossomos , Metoclopramida , Coelhos , Humanos , Animais , Disponibilidade Biológica , Administração Intranasal , Náusea , Lipídeos , Géis , Tamanho da Partícula , Sistemas de Liberação de MedicamentosRESUMO
Obesity is considered one of the most crucial health problems of the century. Therefore, reducing obesity is critically important. Caffeine (CF) and chlorogenic acid (CLA), which are substantial components in green bean coffee which maximize thermogenesis in brown adipose tissue. In our study, we have prepared CF, CLA, and CF + CLA loaded-solid lipid nanoparticles (SLN) since the SLNs are cost-effective, tissue-localized, and highly stable. The central composite design model was preferred to select the optimized formulation. UHPLC was used for quantification related to the CF and CLA amounts. The high-pressure homogenization (HPH) method was used while SLN formulations were prepared in the presence of poloxamer® 407 (surfactant) and Compritol® 888 ATO (solid lipid). The nanoparticles were characterized, followed by the utilization of 3T3-F442A cell lines for the evaluation of the adipogenesis activity of the formulations. Then, rt-PCR and ELISA studies of adipogenic markers were conducted. After optimal formulations were selected with an average of 110.2 ± 0.1 nm, CF (1 mM) + CLA (0.5 mM)-loaded SLN formulation has been proven significantly effective by using PPAR-γ/C/EBP-a pathways. In a nutshell, our study has shown that CF + CLA loaded-SLN has been affected 45.8% times more than regular extracted coffee (p < 0.05) on the adipocyte cells.
Assuntos
Portadores de Fármacos , Nanopartículas , Humanos , Portadores de Fármacos/química , Cafeína/farmacologia , Ácido Clorogênico/farmacologia , Café , PPAR alfa , Nanopartículas/química , Obesidade/tratamento farmacológicoRESUMO
CONTEXT: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. OBJECTIVE: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. METHODS: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. RESULTS: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. CONCLUSION: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).
Assuntos
Sistemas de Liberação de Medicamentos , Tensoativos , Solubilidade , Eplerenona , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Tensoativos/química , Disponibilidade BiológicaRESUMO
Addressing obesity is a critical health concern of the century, necessitating urgent attention. L-carnitine (LC), an essential water-soluble compound, plays a pivotal role in lipid breakdown via ß-oxidation and facilitates the transport of long-chain fatty acids across mitochondrial membranes. However, LC's high hydrophilicity poses challenges to its diffusion through bilayers, resulting in limited bioavailability, a short half-life, and a lack of storage within the body, mandating frequent dosing. In our research, we developed LC-loaded nanoparticle lipid carriers (LC-NLCs) using economically viable and tissue-localized nanostructured lipid carriers (NLCs) to address these limitations. Employing the central composite design model, we optimized the formulation, employing the high-pressure homogenization (HPH) method and incorporating Poloxamer® 407 (surfactant), Compritol® 888 ATO (solid lipid), and oleic acid (liquid oil). A comprehensive assessment of nanoparticle physical attributes was performed, and an open-field test (OFT) was conducted on rats. We employed immunofluorescence assays targeting CRP and PPAR-γ, along with an in vivo rat study utilizing an isolated fat cell line to assess adipogenesis. The optimal formulation, with an average size of 76.4 ± 3.4 nm, was selected due to its significant efficacy in activating the PPAR-γ pathway. Our findings from the OFT revealed noteworthy impacts of LC-NLC formulations (0.1 mg/mL and 0.2 mg/mL) on adipocyte cells, surpassing regular L-carnitine formulations' effects (0.1 mg/mL and 0.2 mg/mL) by 169.26% and 156.63%, respectively (p < 0.05).
Assuntos
Nanopartículas , Nanoestruturas , Ratos , Animais , Lipídeos/química , Carnitina/farmacologia , Portadores de Fármacos/química , Receptores Ativados por Proliferador de Peroxissomo , Nanopartículas/química , Nanoestruturas/química , Tamanho da PartículaRESUMO
Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.
Assuntos
Portadores de Fármacos , Nanopartículas , Humanos , Etabonato de Loteprednol , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Córnea , Tamanho da PartículaRESUMO
AIM: Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. METHODS: SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. RESULTS: It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (â¼0.169 PI) and the mean charge was -23.6. They were found to be stable both physically and chemically at room temperature. CONCLUSION: SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems.
Assuntos
Portadores de Fármacos , Nanopartículas , Lipídeos , Lipossomos , Etabonato de Loteprednol , Tamanho da PartículaRESUMO
Essential oils have a high volatility that leads to evaporation and loss of their pharmacological effect when exposed to the environment. The objectives of the present work were to prepare microcapsules with oregano essential oil by extrusion using sodium alginate as a shell material and non-ionic surfactant polysorbate 80 as an emulsifier to stabilize the emulsion. The present study was aimed to evaluate the physical parameters of microcapsules and to compare the influence of the amount of emulsifier and the essential oil-to-emulsifier ratio on the capsules' physical parameters and encapsulation efficiency; to our knowledge, the existing research had not yet revealed whether unstable emulsion affects the encapsulation efficiency of oregano essential oil. This study showed that increasing the emulsifier amount in the formulation significantly influenced encapsulation efficiency and particle size. Moreover, increasing the emulsion stability positively influenced the encapsulation efficiency. The emulsion creaming index depended on the emulsifier amount in the formulation: the highest creaming index (%) was obtained with the highest amount of polysorbate 80. However, the essential oil-to-polysorbate 80 ratio and essential oil amount did not affect the hardness of the microcapsules (p > 0.05). In conclusion, the obtained results could be promising information for production of microcapsules. Despite the fact that microencapsulation of essential oils is a promising and extremely attractive application area for the pharmaceutical industry, further basic research needs to be carried out.
Assuntos
Alginatos/química , Cápsulas/química , Emulsificantes/química , Emulsões/química , Óleos Voláteis/química , Origanum/química , Polissorbatos/química , Tamanho da PartículaRESUMO
Phenylketonuria (PKU) is a rare inherited metabolic disease characterized by phenylalanine hydroxylase enzyme deficiency. In PKU patients, coenzyme Q10 (CoQ10) levels were found low. Therefore, we focused on the modification of CoQ10 to load the micelles and increase entry of micelles into the cell and mitochondria, and it is taking a part in ATP turnover. Micelles had produced by comparing two different production methods (thin-film layer and direct-dissolution), and characterization studies were performed (zeta potential, size, and encapsulation efficiency). Then, L-arginine (LARG) and poly-arginine (PARG) were incorporated with the micelles for subsequential release and PKU cell studies. The effects of these components on intracellular uptake and their use in the cellular cycle were analyzed by ELISA, Western blot, membrane potential measurement, and flow cytometry methods. In addition, both effects of LARG and PARG micelles on pharmacokinetics at the cellular level and their cell binding rate were determined. The thin-film method was found superior in micelle preparation. PARG/LARG-modified micelles showed sustained release. In the cellular and mitochondrial uptake of CoQ10, CoQ10-micelle + PARG > CoQ10-micelle + LARG > CoQ10-micelle > CoQ10 was found. This increased localization caused lowering of oxygen consumption rates, but maintaining mitochondrial membrane potential. The study results had showed that besides micelle formulation, PARG and LARG are effective in cellular and mitochondrial targeting.
Assuntos
Micelas , Fenilcetonúrias , Humanos , Ubiquinona/química , Mitocôndrias/metabolismo , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/metabolismoRESUMO
The purpose of this study was to conduct the kinetic assessment of iontophoretic delivery of niosomal tetracycline-HCl formulated in an electroconductive gel. Tween-80 and Span-80 were used to obtain tetracycline-HCl niosomes with an average diameter of 101.9 ± 3.3 nm, a polydispersity index of 0.247 ± 0.004, a zeta potential of - 34.1 mV, and an entrapment efficiency of 70.08 ± 0.16%. Four different gel preparations, two of which contained niosomal tetracycline-HCl, were transdermally delivered using Franz diffusion cells under the trigger effect of iontophoresis, applied at 0.2, 0.5, and 1 mA/cm2 current density. The control group was the passive diffusion results of the preparation made using a tetracycline-HCl-based drug marketed in Turkey. The control group was compared with the groups that contained (a) tetracycline-HCl in an electroconductive gel, (b) the niosomal tetracycline-HCl formulation in water, and (c) the niosomal tetracycline-HCl formulation in the electroconductive gel. The group with the niosomal formulation in the electroconductive gel displayed the highest increase in iontophoretic transdermal delivery relative to the control group, displaying a 2-, 2.1-, and 2.2-fold increase, respectively, by current density. The experimental results of transdermal delivery using the synergistic effect of niosomal formulation in electroconductive gel and the trigger effect of iontophoresis appeared to divert slightly from zero-order kinetics, demonstrating a statistically significant increase in the rate of controlled transdermal drug delivery. Considering that about 20% of the formulation is transdermally delivered in the first half-hour, the iontophoretic transdermal delivery of niosomal tetracycline-HCl can be efficiently used in local iontophoretic therapy.
Assuntos
Iontoforese , Tetraciclina , Lipossomos , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodosRESUMO
BACKGROUND: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). METHODS: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. RESULTS: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/ß-catenin pathway. The gene expression level of ß-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3ß signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. CONCLUSION: CNPSGS might be an effective therapeutic alternative for AD treatment.
Assuntos
Alginatos , Doença de Alzheimer , Curcumina , Gelatina , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Impressão Tridimensional , Alicerces Teciduais , Alginatos/química , Gelatina/química , Curcumina/farmacologia , Curcumina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Doença de Alzheimer/tratamento farmacológico , Nanopartículas/química , Alicerces Teciduais/química , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/químicaRESUMO
This research primarily focuses on the development of innovative topical nanoemulsions for etodolac, aimed at surmounting its inherent limitations. The preparation of etodolac nanoemulsions is accomplished through a combination of high shear homogenization and ultrasonication methods. The optimization of the formulation components is systematically conducted using the design of experiments methodology. The droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) of the optimized formulation were assessed using the differential light scattering (DLS) technique. Surface morphology examinations were conducted using electron microscopy, while interactions between excipients and the drug were analyzed through FTIR analysis. Additionally, in vitro release and ex vivo permeability studies were carried out. Furthermore, anti-inflammatory activity was evaluated in the context of a carrageenan-induced paw edema model in rats. The DS, PDI, and ZP of the optimal formulation were 163.5 nm, 0.141, and -33.1 mV, respectively. The in vitro release profile was assessed as a sustained release by following a non-Fickian drug transport. The flux of etodolac nanoemulsions and coarse dispersions were 165.7 ± 11.7 µg/cm2 h and 59.7 ± 15.2 µg/cm2 h, respectively. Enhanced edema inhibition was observed at 13.4%, 36.5%, and 50.65% for the 6th, 8th, and 24th hours, respectively. Taken together, these results confirmed that nanoemulsions are promising carriers for the topical delivery of etodolac.
RESUMO
Ulcerative colitis is an inflammatory condition with ulcerations throughout the colon. The existing remedies have some limitations such as drug inactivation, poor absorption, and adverse reactions. The present study aimed to design novel microsponge formulations to enhance remission of the dexamethasone (as a model pharmaceutical ingredient) in the colon. Microsponges were prepared by using the quasi-emulsion technique. The optimal formulation was selected by applying the design of experiments approach which used methylcellulose (MC) (0.75-2%, w/w), polyvinylalcohol (PVA)(0.5-1%, w/w), and tween 80 (TW80) (1.5-2.5%, w/w). The critical quality attributes were selected as particle size and entrapment efficiency. The particle size and encapsulation efficiency were found as 140.38 ± 9.2 µm and 77.96 ± 3.4 %. After the optimization; morphological, thermal, and physicochemical characterization studies were performed. Ultimately, the optimal formulation was investigated by using the acetic acid-induced ulcerative colitis model in rats. The physicochemical characterization studies confirmed that the formulation components were compatible with each other. The in vitro release mechanisms were fitted to First order kinetics at pH 1.2 (R2:0.9563), and Korsmeyer-Peppas kinetics at pH 4.5 (R2: 0.9877), and pH 6.8 (R2: 0.9706). The medicated microsponges exhibited remarkable recovery compared to the control group of the in vivo ulcerative colitis model (p < 0.05). It could be concluded that microsponges were evaluated as a promising alternative drug delivery system for the management of ulcerative colitis.
Assuntos
Colite Ulcerativa , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ácido Acético/uso terapêutico , DexametasonaRESUMO
The beta-adrenoceptor blocker timolol maleate (TML) is a commonly used pharmaceutical agent for the management of glaucoma. Conventional eye drops have limitations due to biological or pharmaceutical factors. Therefore, TML-loaded ethosomes have been designed to mitigate these restrictions and give a viable solution for reducing elevated intraocular pressure (IOP). The ethosomes were prepared using the thin film hydration method. Integrating the Box-Behnken experimental strategy, the optimal formulation was identified. The physicochemical characterization studies were performed on the optimal formulation. Then, in vitro release and ex vivo permeation studies were conducted. The irritation assessment was also carried out with Hen's Egg Test-Chorioallantoic Membrane model (HET-CAM), and in vivo evaluation of the IOP lowering effect was also performed on rats. The physicochemical characterization studies demonstrated that the components of the formulation were compatible with each other. The particle size, zeta potential, and encapsulation efficiency (EE%) were found as 88.23 ± 1.25 nm, -28.7 ± 2.03 mV, and 89.73 ± 0.42 %, respectively. The in vitro drug release mechanism was found as Korsmeyer-Peppas kinetics (R2 = 0.9923). The HET-CAM findings verified the formulation's eligibility for biological applications. The IOP measurements revealed no statistical difference (p > 0.05) between the once-a-day application of the optimal formulation and the three-times-a-day application of the conventional eye drop. A similar pharmacological response was observed at lowered application frequencies. Therefore, it was concluded that the novel TML-loaded ethosomes could be a safe and efficient alternative for glaucoma treatment.
Assuntos
Glaucoma , Timolol , Animais , Feminino , Ratos , Timolol/química , Pressão Intraocular , Galinhas , Glaucoma/tratamento farmacológico , Antagonistas Adrenérgicos beta , Preparações Farmacêuticas , Soluções OftálmicasRESUMO
Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol®ATO5, and Pluronic® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays.
Assuntos
Galinhas , Olho , Animais , Feminino , Humanos , Membrana Corioalantoide , Sistemas de Liberação de Medicamentos , BioensaioRESUMO
Coenzyme Q10 (CoQ10) is a fat-soluble vitamin-with a benzoquinone-like structure. CoQ10 plays a role in membrane stability, energy conversion, and ATP production. It is also one of the important antioxidants in the body. The bioavailability of exogenous CoQ10 is extremely low due to its poor aqueous solubility and large molecular mass. In this study, mixed proniosomal drug delivery systems have been used to increase solubility and bioavailability of CoQ10. Arginine (semi-essential amino acid) was incorporated in the formulation composition to achieve higher efficacy by boosting nitric oxide presence, endothelial dysfunction, and cellular uptake. Proniosomes were investigated in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, and process yield, and optimization studies were carried on by utilizing STATISTICA 8.0 software considering dependent factors (carrier amount, drug amount, and surfactant ratio). Optimum proniosome formulation (particle size 187.5 ± 16.35 nm, zeta potential: -44.7 ± 12.8 mV, encapsulation efficiency 99.05±0.30%, and product yield: 90.55%) was evaluated for thermal analysis, in-vitro drug release using microcentrifuge method. In-vitro cytotoxicity studies of proniosomes were performed on intestinal Epithelial Cells (Cellartis®, ChiPSC18) and no cytotoxic effects was seen during the 72 h. Besides, anti Alzheimer effect was investigated on APPSL-GFP lentivirus-infected human neural cells (APPSL-GFP-l-HNC) and Alzheimer biomarkers (p-tau181 and p-tau217). While CoQ10's relative bioavailability was statistically increased by proniosome compared to CoQ10 suspension (p<0.01, Grubb test). PK parameters of proniosome formulation, obtained with non-compartmental modeling, were fitting to the data (R2=0.956±0.026). The study results proved that proniosomal formulation has a high potential drug delivery system for both increasing bioavailability and anti-Alzheimer effect of CoQ10.
RESUMO
Objectives: This study constructed dorzolamide (DRZ)-loaded ophthalmic implants for extended drug delivery and increased drug retention. Materials and Methods: Carboxymethyl cellulose (CMC) and chitosan (CHI) were used to describe the ophthalmic implants. The implants were prepared by the solvent casting technique in presence of polyethylene glycol 6000 (PEG 6000) as plasticizer. Physicochemical characterization studies including mechanical characteristics [tensile strength (TS), elongation at break, and Young's modulus], bioadhesion studies, and in vitro and ex vivo drug release studies were conducted. Results: TS of drug-loaded ophthalmic implants was 10.70 and 11.68 MPa, respectively. Elongation at break of CMC and CHI implants was 62.00% and 59.05%, respectively. The in vitro release profiles fit into Higuchi type kinetic model. Ex vivo release study results for both implants were correlated with in vitro release investigations. Conclusion: CMC and CHI-based implants provide extended drug delivery. Implants prepared using CMC provided a significantly slower in vitro release rate, and drug retention on ocular surfaces increased. Thus, it has been concluded that DRZ-loaded CMC implants could provide effective treatment for glaucoma.