Acyclovir-Loaded Solid Lipid Nanoparticles: A Permeation and Penetrability Study

Herpes simplex virus type I is a cutaneous infection treated with acyclovir. The topical treatment has therapeutic challenges due to the deficient delivery of the drug through epithelial barriers. This results in an inadequate drug-virus interaction in the basal epidermis (virus replication site). For this reason, it is essential to generate drug carrier systems that overcome these limitations. In this study, we evaluated the permeation (through in vitro test Franz cells) and penetration (by ex vivo test Tape Stripping) of a topical formulation of acyclovir loaded in solid lipid nanoparticles and a conventional formulation (Aciclor®). The acyclovir solid lipid nanoparticles were prepared using hot homogenization and sonication methods. The results yielded a particle size of 85 ± 2 nm, a polydispersity index of 0.24 ± 0.01, a zeta potential of −16 ± 2 mV, and 94% ± 3% of encapsulated drug. The in vitro test revealed that the permeability of acyclovir solid lipid nanoparticles formulation was superior compared to reference formulation, with values of 1473.74 ± 30.14 µg/cm2 for the solid lipid nanoparticles and 893.36 ± 38.09 µg/cm2 for the reference formulation. The ex vivo test demonstrated that acyclovir solid lipid nanoparticles exhibited superior penetrability through the stratum corneum compared to the reference formulation, with total amounts of 3767 µg for the solid lipid nanoparticles and 2162 µg for the reference formulation. These findings seem promising in advancing new effective therapies against herpes generated by herpes simplex virus type I.

Characteristics and Transdermal Drug Delivery of Triamcinolone-Acetonide-Acetate-Loaded Solid Lipid Nanoparticles Carbomer Gel

Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.

Efficacy of combined albendazol and praziquntel and their loaded solid lipid nanoparticles components in chemoprophylaxis of experimental hydatidosis

Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification.Nanoparticles average size,polydispersity index(PDI),and particle size distribution were determined by scanning electron microscopy(SEM) and photon correlation spectroscopy.Forty females BALB/c were experimentally infected by protoscoleces(PSC) and randomly divided into four equal groups of 10 mice.After the end of the 3 months treatment period and 2 months rest,mice were sacrificed and the peritoneal cavity was opened for removal,counting,measuring,and histological analysis of hydatid cyst.Results:The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%,respectively.The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%,respectively.Conclusions:This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice.

New research on development of solid lipid nanoparticles

To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations of the SLN.the high pressure homogenization(HPH) and the microemulsion tech- nique are to praise highly.The drug incorporation and release profiles could be modified as adjustment of production parameters.The SLNis an excellent drug delivery system and has broad prospects in the phar- maceutical field.

Preparation, optimization, and characterization of chitosancoated solid lipid nanoparticles for ocular drug delivery

The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration.

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC): Occlusive Effect and Penetration Enhancement Ability

Objective: This work compares the occlusive effect and the penetration enhancement ability of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), through in vitro skin. Methods: SLN and NLC were prepared by high shear homogenization and characterized by size, polydispersity index, zeta potential, morphology and physical stability. Occlusive effect was assessed by an in vitro test and by measuring TEWL using pig skin. Skin treated with the lipid carriers was visualized by SEM. A penetration test through skin, followed by tape stripping, was carried out using Nile red as a marker. Results: SLN (200 ± 6 nm) and NLC (192 ± 11 nm) were obtained. An occlusion factor of 36% - 39% was observed for both systems, while a reduction in TEWL of 34.3% ± 14.8% and 26.2% ± 6.5% was seen after treatment with SLN and NLC, respectively. SEM images showed a film formed by the lipid carriers, responsible for the occlusion observed. No differences were found between the occlusive effect produced by SLN and NLC in both tests. NLC allowed the penetration of a greater amount of Nile red than SLN: 4.7 ± 1.3 μg and 1.7 ± 0.4 μg, respectively. Conclusion: Both carriers form a film on the skin, providing an occlusive effect with no differences between these two systems. The penetration of a marker (Nile red) into the stratum corneum was quite higher for NLC than for SLN, suggesting an influence of the composition of these particles on their penetration enhancing ability.

Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy

Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced.

Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form

In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

Bovine Serum Albumin Loaded Solid Lipid Nanoparticles Prepared by Double Emulsion Method

Solid lipid nanoparticles loaded with bovine serum albumin（BSA） were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.

Preparation and Antidiabetic Effect of Orally Administered Nifedipine‐Loaded Solid Lipid Nanoparticles in Fructose-Induced Diabetic Rats

The use of Nifedipine (NI), a dihydropyridine calcium channel blocker, is limited due to its poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN) are known to exhibit suitable pharmacokinetic properties and good biocompatibility. The present investigation was designed to evaluate the effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function in fructose-induced diabetic rats. NI-SLN was prepared by high pressure homogenization technique followed by lyophilization with trehalose as cryoprotectant. Diabetes was induced into rats by the administration of fructose (10%) in drinking water for six weeks. After induction of diabetes, rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or vehicles and their effects on blood glucose levels, oral glucose tolerance test (OGTT), lipid profile, biochemical parameters, electrolytes and histopathology were observed. Single dose administration and treatment with NI-SLN showed significant glucose lowering efficacy in fructose-induced diabetic rats. Although NI and NI-SLN did not alter the fasting blood glucose level in normal rats, diabetic rats treated with NI-SLN resulted in significant reduction in glucose level for 24 hr. In OGTT, NI-SLN exhibited significant antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has better glucose lowering efficacy than that of pure NI in diabetic rats. The survival rates in rats among the treatment groups were 100%. Treatment with NI-SLN significantly improved lipid profiles than NI alone and the effect was dose-dependent. Administration of NI-SLN significantly reduced uric acid, creatinine levels and maintained a good cationic balance. After two weeks of NI-SLN treatment, hepatocytes regained their normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. Therefore, NI-SLN was found to be useful for the enhancement of bioavailability and exhibited profound antidiabetic activity in rats. The results of the study suggested that NI-SLN exerted better improvement in glucose levels, lipid profiles and organ protection than pure NI and might have some beneficial effects in the management of diabetic patients.

Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles： a magnetic resonance imaging study

Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.

<i>In Vivo</i>Pharmacokinetic and Hemocompatible Evaluation of Lyophilization Induced Nifedipine Solid-Lipid Nanoparticle

Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.

聚乙二醇修饰杨梅苷固体脂质纳米粒制备及其体内药动学研究

目的制备聚乙二醇修饰杨梅苷固体脂质纳米粒,并考察其体内药动学。方法高压均质法制备聚乙二醇修饰固体脂质纳米粒,测定包封率、载药量、粒径、Zeta电位,单因素试验优化处方,XRPD进行晶型分析,考察体外释药、稳定性。24只大鼠随机分为4组,分别灌胃给予杨梅苷、杨梅苷固体脂质纳米粒、杨梅苷固体脂质纳米粒+聚乙二醇硬脂酸酯、聚乙二醇修饰杨梅苷固体脂质纳米粒的0.5%CMC-Na混悬液(150 mg/kg),于不同时间点采血,HPLC法测定杨梅素血药浓度,计算主要药动学参数。结果最优处方为药脂比1∶15,单硬酯酸甘油酯与聚乙二醇硬脂酸酯比例10∶1,泊洛沙姆188浓度0.8%,均质次数8次,包封率为81.75%,载药量为5.04%,粒径为207.56 nm,PDI为0.092,Zeta电位为-14.79 mV。杨梅苷以无定型状态存在于聚乙二醇修饰固体脂质纳米粒中,18 h内累积释放度为64.71%,模拟胃液中2 h内、模拟肠液中12 h内稳定性良好。与原料药、固体脂质纳米粒比较,聚乙二醇修饰固体脂质纳米粒t_(max)延长(P<0.05),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.05,P<0.01),相对生物利用度与原料药相比增加至4.60倍。结论聚乙二醇修饰固体脂质纳米粒可改善杨梅苷稳定性,促进其口服吸收。

漆黄素固体脂质纳米粒的制备及体外释放评价

目的制备漆黄素固体脂质纳米粒(FIT-SLN),对其进行质量评价并考察其体外释放作用。方法采用乳化蒸发-低温固化法制备FIT-SLN,利用Box-Behnken设计试验优化处方工艺,并制成冻干粉末。考察其外观、粒径、Zeta电位,并通过差示量热扫描仪判断药物在FIT-SLN冻干粉中的存在状态,透析袋法评价制剂在不同介质中的体外释放行为。结果FIT-SLN的最佳制备工艺:漆黄素用量3 mg、吐温80用量115μL、双硬脂酸甘油酯(Precirol ATO 5)用量30 mg、卵磷脂用量30 mg。所得FIT-SLN的粒径、Zeta电位、包封率分别为(124.53±2.00)nm、(-21.33±1.69)mV、77.89%,体外释放规律与一级动力学方程相符。结论成功制备粒径小、包封率高的FIT-SLN,其具有一定的缓释能力。

脂质纳米粒在经皮给药系统中治疗皮肤病的应用

经皮给药作为一种非侵入性给药方式,正逐渐受到广大医药工作者和患者的青睐。然而,皮肤角质层的屏障功能限制了药物的经皮吸收。脂质纳米粒作为一种新型的药物载体能够有效提高皮肤渗透性、减少药物相关副作用。本文就脂质纳米粒的特点、透皮作用机制以及在多种皮肤病中的应用做一综述,阐明脂质纳米粒在经皮给药领域的广阔发展前景,为脂质纳米粒的开发及临床应用提供参考。

姜黄素固体脂质纳米粒制备工艺研究

采用微乳法制备姜黄素固体脂质纳米粒,以固体脂质总量、2种固体脂质基质的质量比、乳化剂质量、表面活性剂的质量浓度为影响因素进行单因素试验和响应面试验。以姜黄素的包封率和载药量为指标,研究姜黄素固体脂质纳米粒的最优配方。结果表明,姜黄素固体脂质纳米粒优化配方为固体脂质总量30 mg,乳化剂的质量200 mg,表面活性剂质量分数为3%,在此条件下制备的姜黄素固体脂质纳米粒包封率为89.86%,载药量为28.63%。

M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 pandemic.This study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid tumor.The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication.Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth inhibition.These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

Bibliometric mapping of solid lipid nanoparticles research(2012–2022)using VOSviewer

Nanotechnology is a rapidly expanding discipline,and solid lipid nanoparticles(SLN)are at the forefront of this development.They offer various possible clinical and pharmaceutical research applications and numerous other fields.A quantitative review technique called bibliometric analysis uses statistics,data mining,and mathematics to find emerging trends in a particular academic topic.It is currently more widely utilized and is employed in many academic subjects.As a result,the current study looked through Scopus-indexed research documents on SLNs from 2012 to 2022 to assess the growth and expansion of this body of knowledge and predict its course in the future.The VOSviewer package and Scopus Analytics were used to conduct the bibliometric analysis.VOSviewer offers two distinct viewing modes:network and overlay visualization.A total of 3768 journal articles(n=3709)and conference papers(n=59)were extracted.The number of research documents published by 12,367 authors was steadily increasing annually.Gene therapy,development and detection methods,bioavailability,and controlled release have been important research subjects.Souto,E.B.,of the University of Porto in Portugal,is considered the most prolific and frequently cited scholar.Punjab University(India)is the top-publishing institution.India is the leading country in the number of publications and research collaborations.The International Journal of Pharmaceutics is the top source.The current results keep pace with global scientific efforts in nanotechnology and successfully integrate them into the pharmaceutical industry.

固体脂质纳米粒与纳米结构脂质载体的制备和质量评估研究进展

为促进固体脂质纳米粒与纳米结构脂质载体的综合利用,介绍了固体脂质纳米粒与纳米结构脂质载体的结构、组成,并对其生产技术及质量评估进行了详细阐述。固体脂质纳米粒和纳米结构脂质载体是分别以固体脂质或混合脂质为结构核心并伴有表面活性剂稳定水包油结构的脂溶性物质的纳米输送载体。固体脂质纳米粒和纳米结构脂质载体由脂类、乳化剂及其他成分组成,可采用高能制备工艺(高压均质法、微射流法和超声法)和低能制备工艺(变温相转变法、微乳液法、膜接触法和恒温相反转法)制备,其质量评估指标有粒径、Zeta电位、活性分子的负载能力和包封率及脂质基质的结晶行为等。固体脂质纳米粒和纳米结构脂质载体具有低毒性、低生物降解性、高效生物相容性和利于大规模生产的优势,可作为递送载体保护食品或医药中的活性物质。

塞来昔布固体脂质纳米粒对兔角膜重度热烧伤行穿透性角膜移植术后CNV、MMP-2的影响

目的观察塞来昔布(celecoxib,CXB)固体脂质纳米粒(solid lipid nanoparticles,SLN)对兔角膜重度热烧伤(severe corneal thermal burn,SCTB)行穿透性角膜移植术(penetrating keratoplasty,PKP)后角膜新生血管(corneal neovascularization,CNV)及基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)浓度的影响,探讨CXB-SLN对兔SCTB的作用机制。方法取36只新西兰白兔,恒温烧灼器制作兔SCTB模型(左眼),随机分为对照组、PKP组、CXB-PKP组,每组12只。对照组、PKP组球结膜下注射9 g/L的生理盐水0.1 ml,CXB-PKP组球结膜下注射1 g/L的CXB-SLN 0.1 ml。PKP组、CXB-PKP组于造模后第3天行PKP治疗。观察3组白兔术后角膜一般情况并记录术后10、20、40天CNV面积。在术后20、40天各组随机选择6只兔处死。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测角膜上清液中MMP-2浓度,并分析CNV面积与MMP-2的相关性。结果术前3组白兔角膜均可见角膜缘充血明显,角膜烧伤区水肿,混浊,伴角膜上皮层坏死、剥脱。术后对照组可见角膜混浊逐渐加重呈瓷白色混浊,PKP组与CXB-PKP组可见角膜植片均成活,角膜透明度尚可。术后10、20、40天,CXB-PKP组CNV面积小于PKP组(P均<0.05),PKP组CNV面积小于对照组(P均<0.05)。术后20和40天角膜上清液MMP-2的浓度,CXB-PKP组低于PKP组,PKP组低于对照组(P均<0.05)。术后20、40天,CNV面积与MMP-2浓度呈正相关(r=0.742,P<0.001;r=0.827,P<0.001)。结论CXB-SLN对兔SCTB后的CNV具有明显抑制作用,可减轻角膜混浊,其机理可能与MMP-2的下调有关,能够为SCTB后行PKP创造有利条件。