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Polyglycerol dendrimers (PGD) exhibit unique properties such as drug delivery, drug solubilization, bioimaging, and diagnostics. In this study, PGD hydrogels were prepared and evaluated as devices for controlled drug release with good solubilization properties. The PGD hydrogels were prepared by crosslinking using ethylene glycol diglycidylether (EGDGE). The concentrations of EGDGE and PGDs were varied. The hydrogels were swellable in ethanol for loading paclitaxel (PTX). The amount of PTX in the hydrogels increased with the swelling ratio, which is proportional to EGDGE/OH ratio, meaning that heterogeneous crosslinking of PGD made high dense region of PGD molecules in the matrix. The hydrogels remained transparent after loading PTX and standing in water for one day, indicating that PTX was dispersed in the hydrogels without any crystallization in water. The results of FTIR imaging of the PTX-loaded PGD hydrogels revealed good dispersion of PTX in the hydrogel matrix. Sixty percent of the loaded PTX was released in a sink condition within 90 min, suggesting that the solubilized PTX would be useful for controlled release without any precipitation. Polyglycerol dendrimer hydrogels are expected to be applicable for rapid release of poorly water-soluble drugs, e.g., for oral administration.
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In vitro-in vivo correlation (IVIVC) analysis reveals a relationship between in vitro release and in vivo pharmacokinetic response of the drug of interest. Sandostatin LAR Depot (SLD) for endocrine tumors and acromegaly is a sustained-release formulation of octreotide, a cyclic oligomer of 8 amino acids, which prolongs therapeutic efficacy and enhances medication compliance of octreotide. Since the efficacy of SLD is dependent on the pharmacokinetic characteristics of octreotide released from a biodegradable matrix polymer, poly(lactide-co-glycolide)-glucose, of SLD, the IVIVC of SLD is critical for predicting an in vivo behavior of the octreotide. In this study, in vitro release of octreotide from SLD was investigated using the release test media each containing 0.02% or 0.5% surfactant and having different pH values of 7.4 and 5.5. In vivo pharmacokinetic profiles of SLD were determined by LC-MS/MS analysis of the systemic blood concentration of octreotide after the SLD injection to rodents. In IVIVC analysis, the Weibull model was adopted as a drug release model for biodegradable microsphere formulation. The IVIVC analyses revealed the in vitro release test condition of SLD with the highest IVIV correlation coefficient. By applying the in vitro release data to the model derived from the IVIVC analysis, pharmacokinetic parameters of SLD could be predicted with the prediction error of ± 10 ~ 15%. IVIVC analysis and pharmacokinetic prediction model of SLD in our study can be an efficient tool for the development of long-acting pharmaceutical dosage forms.
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Glucose , Octreotida , Aminoácidos , Cromatografia Líquida , Preparações de Ação Retardada/farmacocinética , Microesferas , Poliglactina 910 , Tensoativos , Espectrometria de Massas em TandemRESUMO
GLH8NDE, a derivative of eupatilin, is currently under development to treat dry eye disease. We conducted a randomized, double-masked, placebo-controlled, single- and multiple-day study to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics of ocular GLH8NDE in healthy male adults. Subjects randomly received topical ocular dosing of GLH8NDE or its matching placebo for a day, then for 7 consecutive days with a 62-h washout at one of the following daily doses: 9, 18, 36 (Koreans), and 36 mg (Whites). The study drug was administered in divided doses over 10 h with 2- or 5-h intervals. Thirty-nine (97.5%) out of 40 subjects completed the study. A total of 17 subjects experienced 31 treatment-emergent adverse events, all of which were mild in severity and recovered without sequelae. Neither pathological changes in eye compartments nor clinically significant systemic effects were observed. GLH8NDE was rapidly absorbed reaching the peak concentration within 0.25-0.75 h postdose. The systemic exposure as measured by area under the concentration-time curve from time of administration up to the time of the last quantifiable concentration (AUClast ) after single-day administration of the same dose was 109% higher in Koreans than in Whites. In conclusion, GLH8NDE was safe and well-tolerated in healthy Korean and White male adults at 9-36 mg/day after single- and multiple-day administrations.
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Povo Asiático , Adulto , Área Sob a Curva , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , Humanos , MasculinoRESUMO
Amorphization technology has been the subject of continuous attention in the pharmaceutical industry, as a means to enhance the solubility of poorly water-soluble drugs. Being in a high energy state, amorphous formulations generally display significantly increased apparent solubility as compared to their crystalline counterparts, which may allow them to generate a supersaturated state in the gastrointestinal tract and in turn, improve the bioavailability. Conventionally, hydrophilic polymers have been used as carriers, in which the amorphous drugs were dispersed and stabilized to form polymeric amorphous solid dispersions. However, the technique had its limitations, some of which include the need for a large number of carriers, the tendency to recrystallize during storage, and the possibility of thermal decomposition of the drug during preparation. Therefore, emerging amorphization technologies have focused on the investigation of novel amorphous-stabilizing carriers and preparation methods that can improve the drug loading and the degree of amorphization. This review highlights the recent pharmaceutical approaches utilizing drug amorphization, such as co-amorphous systems, mesoporous particle-based techniques, and in situ amorphization. Recent updates on these technologies in the last five years are discussed with a focus on their characteristics and commercial potential.
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Adenosine (AD), which is used for treating wrinkles, exhibits poor skin permeation. The aim of the present study was to develop a cross-linked silicone-based cellulose elastomer as an elastic artificial skin for the treatment of skin wrinkles, a biocompatible lipid-based nano-carrier for enhancing the skin permeation of AD, and a formulation consisting of the lipid-based carrier incorporated in the elastic artificial skin. AD-loaded solid lipid nanoparticles (SLNs) were prepared using a double-emulsion method. Particle characteristics and mechanical properties of SLNs and elastic artificial skin, respectively, were assessed. Skin permeation was evaluated using SkinEthic RHE tissue, a reconstructed human epidermis model. The mean particle size and zeta potential for SLNs ranged from 123.57 to 248.90 nm and -13.23 to -41.23 mV, respectively. The components of neither SLNs nor the elastic artificial skin were cytotoxic, according to cell- and tissue-viability assays and EU classification. SLNs and the elastic artificial skin exhibited sustained drug release for 48 h. The amount of AD released from SLNs and elastic artificial skin was approximately 10 times and 5 times higher, respectively, than that from AD solution. Therefore, elastic artificial skin incorporated with AD-loaded SLNs may serve as a promising topical delivery system for cosmeceutical treatment of skin wrinkles.
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Eupatilin is known to possess anti-apoptotic, anti-oxidative, and antiinflammatory properties. We report here that eupatilin has a protective effect on the ethanol-induced injury in rats. Sprague-Dawley rats were divided into 6 groups: control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed to determine the extent of liver damage. Total cholesterol (TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis. Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were quantified to verify the degree of inflammation. Based on our findings, chronic alcohol treatment significantly changed the serum indexes and liver indicators of the model rats, which were significantly improved by eupatilin treatment. Rats in the eupatilin-treatment group showed reduced levels of AST, ALT, TG, TC, TNF-α, and IL-1ß, increased SOD activity and GSH levels, and improved overall physiology compared to the alcoholic liver disease model rats. H&E staining also verified the eupatilin-mediated improvement in liver injury. In conclusion, eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatory effects.
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The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus (HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated self-microemulsifying drug delivery system (S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS. Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper self-microemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS. Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.
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This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant.
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Panax ginseng has been used as an herbal medicine for thousands of years. Most of its pharmacological effects are attributed to its constituent ginsenosides, including 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (20(S)-25-OCH3-PPD), which is one of the protopanaxadiol type ginsenosides. It has been found to exhibit anticancer effects by interacting with multiple pharmacological pathways, such as the Wnt/ß-catenin, MDM2, ERK/MAPK, and STAT3 signaling pathways. However, its therapeutic potential could be limited by its low bioavailability mainly due to its low aqueous solubility. Thus, several studies have been conducted on its pharmacokinetics and its delivery systems, so as to increase its oral bioavailability. In this review, comprehensive information on its varying pharmacological pathways in cancer, as well as its pharmacokinetic behavior and pharmaceutical strategies, is provided. This information would be useful in the understanding of its diverse mechanisms and pharmacokinetics as an anticancer drug, leading to the design of superior 20(S)-25-OCH3-PPD-containing formulations that maximize its therapeutic potential.
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As the main symptom of Alzheimer's disease-related dementia is memory loss, patient compliance for donepezil hydrochloride (donepezil), administered as once-daily oral formulations, is poor. Thus, we aimed to design poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) with alginate-coated large pores as an injectable depot of donepezil exhibiting sustained release over 2-3 weeks. The PLGA MS with large pores could provide large space for loading drugs with high loading capacity, and thereby sufficient amounts of drugs were considered to be delivered with minimal use of PLGA MS being injected. However, initial burst release of donepezil from the porous PLGA MS was observed. To reduce this initial burst release, the surface pores were closed with calcium alginate coating using a spray-ionotropic gelation method. The final pore-closed PLGA MS showed in vitro sustained release for approximately 3 weeks, and the initial burst release was remarkably decreased by the calcium alginate coating. In the prediction of plasma drug concentration profiles using convolution method, the mean residence time of the pore-closed PLGA MS was 2.7-fold longer than that of the porous PLGA MS. Therefore, our results reveal that our pore-closed PLGA MS formulation is a promising candidate for the treatment of dementia with high patient compliance.
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Ginsenosides, the major active ingredients of ginseng and other plants of the genus Panax, have been used as natural medicines in the East for a long time; in addition, their popularity in the West has increased owing to their various beneficial pharmacological effects. There is therefore a wealth of literature regarding the pharmacological effects of ginsenosides. In contrast, there are few comprehensive studies that investigate their pharmacokinetic behaviors. This is because ginseng contains the complicated mixture of herbal materials as well as thousands of constituents with complex chemical properties, and ginsenosides undergo multiple biotransformation processes after administration. This is a significant issue as pharmacokinetic studies provide crucial data regarding the efficacy and safety of compounds. Moreover, there have been many difficulties in the development of the optimal dosage regimens of ginsenosides and the evaluation of their interactions with other drugs. Therefore, this review details the pharmacokinetic properties and profiles of ginsenosides determined in various animal models administered through different routes of administration. Such information is valuable for designing specialized delivery systems and determining optimal dosing strategies for ginsenosides.
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In this study, we aimed to design a highly swellable and mechanically robust matrix tablet (SMT) as a gastroretentive drug-delivery system (GRDDS) capable of improving the dissolution behavior of ß-lapachone with low aqueous solubility. For the preparation of SMTs, the cogrinding technique and freeze-thaw method were used to disperse ß-lapachone in SMTs in an amorphous state and to enhance the swelling and mechanical properties of SMTs, respectively. As a result, the crystallinity of coground ß-lapachone incorporated in the SMTs was found to be considerably decreased; thereby, the dissolution rates of the drug in a simulated gastric fluid could be substantially increased. The SMTs of ß-lapachone also demonstrated significantly enhanced swelling and mechanical properties compared to those of a marketed product. The reason for this might be because the physically crosslinked polymeric networks with a porous structure that were formed in SMTs through the freeze-thaw method. In addition, ß-lapachone was gradually released from the SMTs in 6 h. Therefore, SMTs of ß-lapachone developed in this study could be used as GRDDS with appropriate swelling and mechanical properties for improving the dissolution behavior of hydrophobic drugs such as ß-lapachone.
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Our study aimed to investigate the effects of the polysaccharide-rich extract of Phragmites rhizoma (PEP) against water immersion restraint (WIR) stress and forced swimming-induced fatigue. Exposure to WIR stress significantly increased the ulcer index, bleeding score, the weight of the adrenal gland, blood glucose concentrations, total cholesterol, cortisol, and creatine kinase (CK). The weight of the spleen decreased significantly. In addition, myeloperoxidase (MPO) and thiobarbituric acid-reactive substance (TBARS) were significantly upregulated by WIR stress. The antioxidative factors such as glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the stomach were decreased by WIR stress. Alterations induced by WIR stress were effectively reversed by pretreatment with PEP. The swimming endurance capacity of mice was significantly prolonged by the oral administration of PEP. Swimming-induced fatigue significantly reduced the body weight; however, the injection of PEP inhibited the decrease of body weight. The PEP-treated group had significantly lower CK levels in plasma, an indicator of muscle damage. These results indicated that PEP has anti-stress and anti-fatigue effects, which are mediated by suppressing the hyperactivation of the hypothalamus-pituitary-adrenal axis, and antagonism of the oxidative damages induced by WIR stress and prolonged swimming times.
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Fadiga/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Poaceae/química , Polissacarídeos/administração & dosagem , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Fadiga/metabolismo , Fadiga/fisiopatologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Peroxidase/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Rizoma/química , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , NataçãoRESUMO
Itraconazole (ITZ) is an anti-fungal agent generally used to treat cutaneous mycoses. For efficient delivery of ITZ to the skin tissues, an oil-in-water (O/W) cream formulation was developed. The O/W cream base was designed based on the solubility measurement of ITZ in various excipients. A physical mixture of the O/W cream base and ITZ was also prepared as a control formulation to evaluate the effects of the solubilized state of ITZ in cream base on the in vitro skin deposition behavior of ITZ. Polarized light microscopy and differential scanning calorimetry demonstrated that ITZ was fully solubilized in the O/W cream formulation. The O/W cream formulation exhibited considerably enhanced deposition of ITZ in the stratum corneum, epidermis, and dermis compared with that of the physical mixture, largely owing to its high solubilization capacity for ITZ. Therefore, the O/W cream formulation of ITZ developed in this study is promising for the treatment of cutaneous mycoses caused by fungi such as dermatophytes and yeasts.
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This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.
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Bladder dysfunction is a common complication of diabetes mellitus (DM). However, there have been a few studies evaluating bladder smooth muscle contraction in DM in the presence of pharmacological inhibitors. In the present study, we compared the contractility of bladder smooth muscle from normal rats and DM rats. Furthermore, we utilized pharmacological inhibitors to delineate the mechanisms underlying bladder muscle differences between normal and DM rats. DM was established in 14 days after using a single injection of streptozotocin (65 mg/kg, intraperitoneal) in Sprague-Dawley rats. Bladder smooth muscle contraction was induced electrically using electrical field stimulation consisting of pulse trains at an amplitude of 40 V and pulse duration of 1 ms at frequencies of 2-10 Hz. In this study, the pharmacological inhibitors atropine (muscarinic receptor antagonist), U73122 (phospholipase C inhibitor), DPCPX (adenosine A1 receptor antagonist), udenafil (PDE5 inhibitor), prazosin (α1-receptor antagonist), verapamil (calcium channel blocker), and chelerythrine (protein kinase C inhibitor) were used to pretreat bladder smooth muscles. It was found that the contractility of bladder smooth muscles from DM rats was lower than that of normal rats. In addition, there were significant differences in percent change of contractility between normal and DM rats following pretreatment with prazosin, udenafil, verapamil, and U73122. In conclusion, we suggest that the decreased bladder muscle contractility in DM rats was a result of perturbations in PLC/IP3-mediated intracellular Ca2+ release and PDE5 activity.
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Ginsenosides, dammarane-type triterpene saponins obtained from ginseng, have been used as a natural medicine for many years in the Orient due to their various pharmacological activities. However, the therapeutic potential of ginsenosides has been largely limited by the low bioavailability of the natural products caused mainly by low aqueous solubility, poor biomembrane permeability, instability in the gastrointestinal tract, and extensive metabolism in the body. To enhance the bioavailability of ginsenosides, diverse micro-/nano-sized delivery systems such as emulsions, polymeric particles, and vesicular systems have been investigated. The delivery systems improved the bioavailability of ginsenosides by enhancing solubility, permeability, and stability of the natural products. This mini-review aims to provide comprehensive information on the micro-/nano-sized delivery systems for increasing the bioavailability of ginsenosides, which may be helpful for designing better delivery systems to maximize the versatile therapeutic potential of ginsenosides.
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This study aimed to develop porous microspheres with a suitable porous structure and mechanical property for cell delivery using a comparatively low molecular weight (MW) poly(lactide-co-glycolide) (PLGA) having a weak mechanical strength and fast degradation rate, which could be potentially used for treatment of corneal endothelial diseases. Porous microspheres of 30 kDa PLGA with different pore sizes were prepared by varying preparation conditions, and the microspheres with mean pore diameters approximately 0.5, 1, 2 and 3 times that of a single green fluorescent protein-expressing human embryonic kidney 293 cell, used as a model cell, were chosen for cell loading study. The microspheres with an average pore diameter two times greater than that of the single cell were found to be the most appropriate for efficient cell loading in the inner pore spaces, along with demonstrating a good mechanical property, injectability and biodegradability. To maximize the cell loading amount in the microspheres, the cell adhesive property of the microspheres and cell loading conditions were optimized, leading to approximately 4.2 times increase in the cell loading amount. The porous microspheres designed using the low MW PLGA hold promise as a delivery system of corneal endothelial cells for regeneration of the corneal endothelium.
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Células Imobilizadas/transplante , Células Endoteliais/transplante , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polilisina/química , Células Imobilizadas/metabolismo , Córnea/irrigação sanguínea , Córnea/metabolismo , Córnea/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio/metabolismo , Endotélio/patologia , Células HEK293 , Humanos , PorosidadeRESUMO
BACKGROUND: Nanocrystallization technologies have been widely studied in recent years, as the formulation of drug nanocrystals solves problems of poor drug solubility and bioavailability. However, drug nanocrystals in the size range of 1-1000 nm usually need to be accompanied by stabilizers, such as polymers or surfactants, to enhance their stability. Despite their simplicity, improved dissolution rate, and enhanced bioavailability, the limited stability of nanocrystal formulations has prevented further development. OBJECTIVE: The most effective way to handle this instability is to use stabilizers. This paper reviews various factors to consider for the production of stable drug nanocrystals and provides suggestions to overcome the problems associated with instability, such as aggregation and Ostwald ripening. Through various examples of stabilizers acting via electrostatic and steric stabilization, this review highlights the scope of enhancing the stability of drug nanocrystals. CONCLUSION: Studies on stabilizers used in the production of drug nanocrystals are ongoing; various factors, such as the effect of zeta potential on the stability of drug nanosuspensions, have already been revealed. However, it is necessary to determine the most appropriate stabilizer experimentally based on the various mechanisms and factors have been reviewed since the possible interactions between each drug and stabilizer are diverse.
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Nanopartículas/química , Preparações Farmacêuticas/química , Disponibilidade Biológica , Cristalização , Estabilidade de Medicamentos , SolubilidadeRESUMO
Tuberculosis remains a serious health problem worldwide. Characterization of the dendritic cell (DC)-activating mycobacterial proteins has driven the development of effective TB vaccine candidates besides improving the understanding of immune responses. Some studies have emphasized the essential role of protein Rv2220 from M. tuberculosis in mycobacterial growth. Nonetheless, little is known about cellular immune responses to Rv2220. In this study, our aim was to test whether protein Rv2220 induces maturation and activation of DCs. Rv2220-activated DCs appeared to be in a mature state with elevated expression of relevant surface molecules and proinflammatory cytokines. DC maturation caused by Rv2220 was mediated by MAPK and NF-κB signaling pathways. Specifically, Rv2220-matured DCs induced the expansion of memory CD62LlowCD44highCD4+ T cells in the spleen of mycobacteria-infected mice. Our results suggest that Rv2220 regulates host immune responses through maturation of DCs, a finding that points to a new vaccine candidate against tuberculosis.