Characterization of silver sulfadiazine-loaded solid lipid nanoparticles by thermal analysis

The aim of this study is the solid-state characterization of solid lipid nanoparticles (SLN) based on Compritol^® 888 (C888) and Lutrol^® F68 (F68), loaded with silver sulfadiazine (AgSD), used to develop sponge-like dressings to treat chronic skin ulcers such as decubitis and leg ulcers. Silver compounds like AgSD, in fact, are used to prevent and/or to treat wound colonization that could impair healing, also in the case of antibiotic-resistant bacteria. Thermal analysis, with support from powder X-ray diffractometry and Fourier transform infrared spectroscopy, is used to characterize lipid and drug bulk, unloaded and drug-loaded SLN. In particular, differential scanning calorimetry is used to investigate the degree of crystallinity and the solid-state modification of lipid, two parameters correlated to drug incorporation and drug release rates. The solid-state characterization demonstrates AgSD entrapment in C888 as a core enclosed into F68 shell. AgSD SLN are also stored at different temperatures 25 and 37 °C, respectively, to study the effect of storage conditions, that induce an increase of the lipid crystallinity index correlated to drug release from the lipid matrix.     

七元瓜环作为5-氨基水杨酸结肠给药载体可行性考察

利用荧光光谱法考察了七元瓜环(Q[7])和5-氨基水杨酸(5-ASA)在不同pH条件下的相互作用. 在pH＝2.0, 4.0时, Q[7]与5-ASA可形成1∶1(物质的量比)的包合物; 而在pH＝5.0, 6.0, 7.4 时未观察到两者之间有明显的相互作用. 利用¹H NMR 技术研究了Q[7]-5-ASA固体包合物不同pH值的存在形式. 当体系的pH＜6.0, 5-ASA以包合物的形式存在. 而当pH＞6.0, 包合物的稳定性下降, 5-ASA被释放出来以游离的药物分子形式存在, 说明5-ASA与Q[7]之间的相互作用依赖于体系的pH值, Q[7]可作为5-ASA结肠给药的一种潜在载体; 热动力学的研究表明包合作用主要受到体系焓变的影响; 红外光谱, DSC和TG的分析进一步证实了Q[7]-5-ASA固体包合物的形成.     

Antioxidant and antimicrobial activities of green tea extract loaded into nanostructured lipid carriers

In this paper, the preparation and characterization of some novel nanostructured lipid carriers for drug delivery are reported. They are obtained by mixing two solid lipids, cetyl palmitate and glyceryl stearate, with three types of vegetable oils: grape seed oil, St. John's wort oil (Hypericum perforatum oil) and sea buckthorn oil. In order to increase their antioxidant and antimicrobial properties, they are co-loaded with green tea extract by using a modified high shear homogenization technique. Size distribution and polydispersity index of the developed nanostructured lipid carriers determined by the dynamic light scattering, and corroborated with the results obtained by the transmission electron microscopy analysis, confirmed that the structures obtained are at nanoscales. The crystallinity behavior of the prepared nanostructured lipid carriers has been studied by differential scanning calorimetry; zeta potential measurements show that all loaded nanostructures present excellent physical stability. Their antioxidant and antimicrobial properties evaluated by an appropriate in vitro analysis using the chemiluminescence method, and the diffusion disc method, respectively, show that green tea extract could be utilized as a valuable natural source of antioxidant and antimicrobial agent. These new nano-formulations proved to have significant potential for nutritional and pharmaceutical applications.     

Thermal characterization and compatibility studies of itraconazole and excipients for development of solid lipid nanoparticles

The current study was performed to investigate possible interactions between triazole antifungal drug itraconazole (ITR) with selected excipients commonly used for development of solid lipid nanoparticles. The excipients included common lipids (glyceryl behenate (Compritol 888 ATO?), glyceryl monostearate, stearic acid, and cetyl palmitate), charge inducers (dicetyl phosphate and stearlyamine), and surfactants (sodium cholate and sodium deoxycholate). Differential scanning calorimetry, isothermal stress testing, Fourier transform infrared spectral analysis, optical microcopy, and X-ray powder diffraction analysis were performed for assessing the compatibility between the drug and the excipients. Results of the study suggest that the stearic acid exhibited drug–excipient interactions, whereas all other excipients used in the study were found to be compatible with ITR.     

Composite Hydrogels for Sustained Release of Therapeutic Agents

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hydrogel composites were prepared by embedding drug‐loaded, biodegradable poly (DL‐lactide‐co‐glycolide) (PLGA) microparticles in semicrystalline hydrogels of polyvinyl alcohol (PVA). The gels were physically cross‐linked by the formation of the crystallites. The presence of the crystallites and the composite nature of the structure were confirmed by using differential scanning calorimetry and ATR‐FTIR spectroscopy. The distribution of microparticles in the hydrogel matrix was evaluated by using confocal laser scanning microscopy with coumarin‐6 as a fluorescence marker. The numbers of particles in the hydrogel matrix increased along the scanning depth, indicating uneven distribution. The release behavior of a model therapeutic agent, hydrocortisone, was evaluated, and the hydrogel composite system provided for better control of release than the microparticles and hydrogels alone. The addition of outer layers of PVA to the original single‐layer composite further reduced the initial burst effect from the microparticles and allowed for a linear release profile for greater than 1 month.     

Crystallinity of Dynasan<Superscript>®</Superscript>114 and Dynasan<Superscript>®</Superscript>118 matrices for the production of stable Miglyol<Superscript>®</Superscript>-loaded nanoparticles

This study focuses on the physicochemical characterization of lipid materials useful for the production of the so-called solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The chosen lipids were Dynasan^®114 (glyceril trimyristate) and Dynasan^®118 (glyceril tristearate) as solid lipids (SL), melting temperature above 80 °C, and Miglyol^®812 (caprylic/capric triglyceride) and Miglyol^®840 (propylene glycol dicaprylate/dicaprate) as liquid lipids (LL), crystallizing below ?15 °C. Raw lipids (pure or SL:LL mixtures) were analyzed by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD), and Polarized Light Microscopy (PLM), before and after tempering at 80 °C for 1 h. The selected SL:LL combination was 70% (Dynasan^®114 and 118) and 30% (Miglyol^®812 and 840) for the production of SLN and NLC by high-pressure homogenization (HPH), respectively. Particles with a mean size of 200 nm (polydispersity index <0.329) and zeta potential of ?15 mV were obtained, and their long-term stability was confirmed for 3 months of storage at 7 °C.     

Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables

This study aimed to prepare solid lipid nanoparticles (SLNs) of a hydrophobic drug, tretinoin, by emulsification-ultrasonication method. Solubility of tretinoin in the solid lipids was examined. Effects of process variables were investigated on particle size, polydispersity index (PI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (L) of the SLNs. Shape and surface morphology of the SLNs were investigated by cryogenic field emission scanning electron microscopy (cryo-FESEM). Complete encapsulation of drug in the nanoparticles was checked by cross-polarized light microscopy and differential scanning calorimetry (DSC). Crystallinity of the formulation was analyzed by DSC and powder X-ray diffraction (PXRD). In addition, drug release and stability studies were also performed. The results indicated that 10mg tretinoin was soluble in 0.45±0.07 g Precirol? ATO5 and 0.36±0.06 g Compritol? 888ATO, respectively. Process variables exhibited significant influence in producing SLNs. SLNs with <120 nm size, <0.2 PI, >I30I mV ZP, >75% EE, and ～0.8% L can be produced following the appropriate formulation conditions. Cryo-FESEM study showed spherical particles with smooth surface. Cross-polarized light microscopy study revealed that drug crystals in the external aqueous phase were absent when the SLNs were prepared at ≤0.05% drug concentration. DSC and PXRD studies indicated complete drug encapsulation within the nanoparticle matrix as amorphous form. The drug release study demonstrated sustained/prolonged drug release from the SLNs. Furthermore, tretinoin-loaded SLNs were stable for 3 months at 4°C. Hence, the developed SLNs can be used as drug carrier for sustained/prolonged drug release and/or to improve oral absorption/bioavailability.     

Thermal analysis and compatibility studies of prednicarbate with excipients used in semi solid pharmaceutical form

Differential Scanning Calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG) and infrared spectroscopy (IR) techniques were used to investigate the compatibility between prednicarbate and several excipients commonly used in semi solid pharmaceutical form. The thermoanalytical studies of 1:1 (m/m) drug/excipient physical mixtures showed that the beginning of the first thermal decomposition stage of the prednicarbate (T _onset value) was decreased in the presence of stearyl alcohol and glyceryl stearate compared to the drug alone. For the binary mixture of drug/sodium pirrolidone carboxilate the first thermal decomposition stage was not changed, however the DTG peak temperature (T _{peak DTG}) decreased. The comparison of the IR spectra of the drug, the physical mixtures and of the thermally treated samples confirmed the thermal decomposition of prednicarbate. By the comparison of the thermal profiles of 1:1 prednicarbate:excipients mixtures (methylparaben, propylparaben, carbomer 940, acrylate crosspolymer, lactic acid, light liquid paraffin, isopropyl palmitate, myristyl lactate and cetyl alcohol) no interaction was observed.     

Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells

Four types of drug nanoparticles (NPs) based on amphiphilic hyperbranched block copolymers were developed for the delivery of the chemotherapeutic doxorubicin (DOX) to breast cancer cells. These carriers have their hydrophobic interior layer composed of the hyperbranched aliphatic polyester, Boltorn^® H30 or Boltorn^® H40, that are polymers of poly 2,2‐bis (methylol) propionic acid (bis‐MPA), while the outer hydrophilic shell was composed of about 5 poly(ethylene glycol) (PEG) segments of 5 or 10 kDa molecular weight. A chemotherapeutic drug DOX, was further encapsulated in the interior of these polymer micelles and was shown to exhibit a controlled release profile. Dynamic light scattering and transmission electron microscopy analysis confirmed that the NPs were uniformly sized with a mean hydrodynamic diameter around 110 nm. DOX‐loaded H30‐PEG10k NPs exhibited controlled release over longer periods of time and greater cytotoxicity compared with the other materials developed against our tested breast cancer cell lines. Additionally, flow cytometry and confocal scanning laser microscopy studies indicated that the cancer cells could internalize the DOX‐loaded H30‐PEG10k NPs, which contributed to the sustained drug release, and induced more apoptosis than free DOX did. These findings indicate that the H30‐PEG10k NPs may offer a very promising approach for delivering drugs to cancer cells. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Novel Supports Based on Polysaccharides for Sustained‐Release of Isosorbide Dinitrate

Novel supports based on carboxymethylcellulose (CMC), crosslinked with epichlorohydrin (EPC), and microparticles based on acetylphthalylcellulose (APC), for sustained‐release of isosorbide dinitrate (Isoket, Ik), were obtained. The drug has been included into CMC hydrogels through diffusion from ethanol‐water solution. Studies about the ethanol–water ratio influence on including the drug have shown an increased amount of included drug at higher content of water in the alcohol‐water mixture. Isoket–ACP microparticles have been obtained by drug and polymer co‐precipitation from emulsified aqueous solution.

The kinetics for “in vitro” release of Ik from polymeric materials, in simulated conditions for intestinal tract medium, where the drug is preferentially absorbed, has been analyzed. The experimental data have shown a “zero” order kinetic for drug release, which is characteristic for systems controlled by diffusion.     

Nanoparticles Synthesis from Corn Cob (Xylan) and Their Potential Application as Colon-Specific Drug Carrier

Summary: Corn Cob based Xylan, a natural polysaccharide extracted from agro-waste may be used as a tool to deliver drugs especially to the colon because of their timely retention in the physiological environment of stomach and small intestine and can only be degraded in colon by vast anaerobic microflora like bifidobacterium. The objective of present research study is to incorporate the drug namely 5-aminosalicylic acid (5-ASA) into xylan macromolecular backbone, either by surface adsorption or by intermolecular covalent bond formation so that absorption of drugs is prevented in upper gastrointestinal tract (GIT). To achieve the above objective, xylan prodrug of 5-ASA was synthesized via activation of carboxylic acid with N,N-carbonyldiimidazole. The structure of obtained xylan prodrug was evaluated by means FT-IR spectroscopy. The ester carbonyl absorption band was observed at 1690 cm⁻¹ in addition to the bands originated from 5-ASA and xylan. The resulting prodrug and xylan itself assembled into spherical nanoparticles were analyzed by scanning electron microscopy. The prodrug of 5-ASA was synthesized which might be active against inflammatory bowel diseases, a novel thought towards advanced drug delivery from xylan based nanoparticles will be presented.     

Fabrication,characterization and evaluation of bacterial cellulose-based capsule shells for oral drug delivery

Bacterial cellulose (BC) was investigated for the first time for the preparation of capsule shells for immediate and sustained release of drugs. The prepared capsule shells were characterized using X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. The BC capsule shells were studied for drug release using an USP type-I dissolution apparatus. Irrespective of the drying method and the thickness of the BC sheet, the capsule shells displayed an immediate drug release profile. Moreover, the addition of release-retardant cellulosic polymers sustained the drug release having first-order kinetics for hydroxypropylmethylcellulose and carboxymethyl cellulose sodium with R ² values of 0.9995 and 0.9954, respectively. Furthermore, these capsules shells remained buoyant in 0.1 N HCl (pH 1.2) solution up to 12 h. This study showed that BC is a promising alternative to gelatin capsules with both immediate and sustained drug release properties depending upon the compositions of the encapsulated materials.     

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.     

Modification and stabilizing effects of PEG on resveratrol-loaded solid lipid nanoparticles

Resveratrol-loaded solid lipid nanoparticles (SLNs) modified by polyethylene glycol (PEG2000) (RES–PEG–SLNs) were prepared to study the stabilizing influences of PEG2000 on SLNs properties including loading capacity, particle size, photostability, and release. The micromorphology, particle size distribution, drug–lipid–modifier interaction and crystalline structure were characterized to elucidate stabilizing effects of PEG2000 on SLNs. Compared with ordinary SLNs, SLNs modified by PEG2000 at relatively low amounts of [m(PEG2000):m(lipids) = 1:10] exhibit high drug loading, steady nanoparticle size distributions, photostability and sustained release. According to characterizations, RES–PEG–SLNs formation is dependent on the physical interactions of drug–lipid–modifier. Since PEG2000 is doped into lipid matrix in a non-crystalline state, the lipids crystalline arrangement is disrupted. Additionally, RES–PEG–SLNs are crystallized in a PEG2000/lipid eutectic mixture rather than a simple mixture, inhibiting the lipid polymorphism transformation from α- to β-form, and therefore preventing drug exclusion from the lipid matrix. The PEG2000/lipid matrix contains lattice defects, which allow for the incorporation of more resveratrol and preventing it from photodegradation effectively. In contrast to the burst release of SLNs modified without PEG2000, resveratrol is released more slowly from the lattice defects in lipid matrix of RES–PEG–SLNs, resulting in a sustained release fitted by a two-stage exponential kinetic equation. PEG2000 is distributed on the RES–PEG–SLNs surface, increasing repulsion between nanoparticles and avoiding particles aggregation. These results confirm that both matrix doping effects and surface steric hindrance produced by the presence of PEG2000 play important roles in maintaining high loadings, nanoparticle size, photostability and sustained release.     

魔芋葡甘聚糖/聚乙烯醇纳米纤维膜及其释药行为研究

为了研制药物缓释效果优良的薄膜材料,利用静电纺丝设备研制不同比重的魔芋葡甘露聚糖/聚乙烯醇纳米纤维膜,并通过扫描电镜、傅里叶变换红外光谱和示差扫描量热法表征纳米纤维膜的结构和性能,结合体外实验和数学模型研究其缓释行为.结果显示当魔芋葡甘露聚糖含量占纳米纤维膜总质量约76%时,纳米纤维膜中微纤丝粗细最均匀且结点较少,纳米纤维膜中魔芋葡甘聚糖和聚乙烯醇之间存在明显的相互作用,含有5-氨基水杨酸的纳米纤维膜在pH=7.4 PBS磷酸盐缓冲液中25 h的累积释放量大约为45%,显示出良好的药物缓释效果,其缓释行为与Higuchi模型具有较高的拟合度.研究表明利用静电纺丝设备研制的魔芋葡甘聚糖/聚乙烯醇纳米纤维膜可以为药物缓释载体的开发提供理论依据.     

Effect of vegetable oils on obtaining lipid nanocarriers for sea buckthorn extract encapsulation

The principal aim of the present study was to develop new safe and highly antioxidant nanostructured lipid carriers loaded with sea buckthorn extract. Three vegetable oils — grape seed oil, sea buckthorn oil and St. John's wort oil (Hypericum perforatum oil) — were used as matrix components and the modified high shear homogenization technique has been employed for the synthesis of nanostructured materials. The effect of these oils on the antioxidant and antimicrobial activities of loaded sea buckthorn extract — nanostructured lipid carriers — has also been studied. For this purpose, a combination of two solid lipids: cetyl palmitate with glyceryl stearate and lecithin/block copolymer has been used. The obtained nanostructured lipid carriers have been characterized for the particle size and zeta potential by means of dynamic light scattering measurements. The nano-dimension morphology of loaded nanostructured lipid carriers was confirmed by transmission electron microscopy. Their crystallinity measured by differential scanning calorimetry has revealed a high disordered lipid matrix. The properties of sea-buckthorn-extract-loaded nanoparticles have been evaluated by an appropriate in vitro analysis (chemiluminescence method). The presence of the three vegetable oils influences extensively the antioxidant properties of the developed nano-formulations, as has been demonstrated using the chemiluminescence technique. The antimicrobial activity of the studied nanostructured lipid carriers, analyzed by the diffusion disc method, shows in most of the samples a high efficiency against Escherichia coli bacteria.     

Food dyes screening using electrochemistry approach in solid state: the case of sunset yellow dye electrochemical behavior

Concerning the importance of the identification and characterization of food dyes in food science, this work presents a screening method using voltammetry of immobilized microparticles for identification in solid state of sunset yellow, tartrazine yellow, brilliant blue, indigotine, and erythrosine in food matrices. Different aqueous supporting electrolyte were investigated for screening purpose and NaCl 0.1 mol L⁻¹ showed to be suitable for evaluating dyes in solid state. By using square wave voltammetry as detection mode was possible to establish qualitative diagnostic criteria for identification of dyes in commercials powder of food dyes samples using both anodic and cathodic scan. Moreover, based on the solid-state electrochemistry profile and due to the lack of information about the electrochemical behavior of these compounds in solid state, some oxi/reduction pathways could be elucidated, and special attention was given to the case of sunset yellow dye.

     

Evaluation of network parameters and drug release behavior of gum acacia-crosslinked-carbopol hydrogel wound dressings

Present article discusses the synthesis, characterization, biodegradation, network parameter and drug release of gum acacia-crosslinked-carbopol hydrogel wound dressing. Polymers have been characterized by ¹³C solid state nuclear magnetic resonance spectroscopy, elemental analysis, cryo-scanning electron microscopy, atomic force microscopy, thermogravimetric analysis, differential thermal analysis, differential thermogravimetry, and differential scanning calorimetry studies. Network parameters of hydrogel wound dressings such as polymer volume fraction in the swollen state φ, Flory–Huggins interaction parameter χ, molecular weight of the polymer chain between two neighboring cross links M_c, crosslink density ρ and the corresponding mesh size ξ have also been determined. Different in vitro release kinetic models (zero order, first order, Higuchi square root law, Korsmeyer-Peppas, and Hixson-Crowell cube root models) have been applied on the drug release profile. The release of antibiotic drug moxifloxacin from the drug loaded hydrogel matrix occurred through non-Fickian diffusion mechanism and release profile best fitted in the Korsmeyer-Peppas model. Semi-contact mode atomic force microscopic imaging showed that rough surface with root mean square roughness 82.868 nm of the polymer films.     

Interaction of Liposomal Formulations of Meta-tetra(hydroxyphenyl)chlorin (Temoporfin) with Serum Proteins: Protein Binding and Liposome Destruction

mTHPC is a non polar photosensitizer used in photodynamic therapy. To improve its solubility and pharmacokinetic properties, liposomes were proposed as drug carriers. Binding of liposomal mTHPC to serum proteins and stability of drug carriers in serum are of major importance for PDT efficacy; however, neither was reported before. We studied drug binding to human serum proteins using size‐exclusion chromatography. Liposomes destruction in human serum was measured by nanoparticle tracking analysis (NTA). Inclusion of mTHPC into conventional (Foslip^®) and PEGylated (Fospeg^®) liposomes does not affect equilibrium serum protein binding compared with solvent‐based mTHPC. At short incubation times the redistribution of mTHPC from Foslip^® and Fospeg^® proceeds by both drug release and liposomes destruction. At longer incubation times, the drug redistributes only by release. The release of mTHPC from PEGylated vesicles is delayed compared with conventional liposomes, alongside with greatly decreased liposomes destruction. Thus, for long‐circulation times the pharmacokinetic behavior of Fospeg^® could be influenced by a combination of protein‐ and liposome‐bound drug. The study highlights the modes of interaction of photosensitizer‐loaded nanovesicles in serum to predict optimal drug delivery and behavior in vivo in preclinical models, as well as the novel application of NTA to assess the destruction of liposomes.     

Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification

Nanostructured lipid carriers (NLC) made from mixtures of solid and spatially incompatible liquid lipids were prepared by melt-emulsification. Their drug loading capacity and releasing properties of progesterone were compared with those of solid lipid nanoparticles (SLN), and the NLC prepared by solvent diffusion method. Monostearin (MS) and stearic acid (SA) were used as solid lipid, whilst the oleic acid (OA) was used as liquid lipid. Properties of carriers such as the particle size and its distribution, drug loading, drug encapsulation efficiency and drug release behavior were investigated. As a result, the drug encapsulation efficiencies were improved by adding the liquid lipid into the solid lipid of nanoparticles. The drug release behavior could be adjusted by the addition of liquid lipid, and the NLC with higher OA content showed the faster rate of drug releasing. NLC had higher efficiency of encapsulation and slower rate of drug release than those of NLC prepared by solvent diffusion method. On the other hand, the NLC with higher drug loading was obtained, though the drug encapsulation efficiency was decreased slightly due to the increase of the amount of drug. The NLC modified with polyethylene glycol (PEG) was also prepared by using polyethylene glycol monostearate (PEG-SA). It was observed that the incorporation of PEG-SA reduced the drug encapsulation efficiency, but increased the rate of drug release. A sample with almost complete drug release in 24 h was obtained by modifying with 1.30 mol% PEG-SA. It indicated that the modified NLC was a potential drug delivery system for oral administration.