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.

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.

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.

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.

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.

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.

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.

Bimodal visualization of colorectal uptake of nanoparticles in dimethylhydrazine-treated mice

AIM:To investigate colorectal uptake of solid lipid nanoparticles(SLNs) in mice receiving different doses of 1,2-dimethylhydrazine(DMH) using magnetic resonance(MR) and laser-scanning confocal fluorescence microscope(LSCFM) imaging.METHODS:Eight mice were sacrificed in a pilot study to establish the experimental protocol and to visualize colorectal uptake of SLNs in normal mice.Gadopentetate dimeglumine and fluorescein isothiocyanate(FITC)-loaded SLN(Gd-FITC-SLN) enemas were performed on mice receiving DMH for 10 wk(group 1,n = 9) or 16 wk(group 2,n = 7) and FITC-SLN enema wasperformed on 4 DMH-treated mice(group 3).Pre-and post-enema MR examinations were made to visualize the air-inflated distal colorectum.Histological and LSCFM examinations were performed to verify colorectal malignancy and to track the distribution of SLNs.RESULTS:Homogeneous enhancement and dense fluorescence(FITC) deposition in colorectal wall were observed in normal mice and 1 DMH-treated mouse(group 1) on fluid attenuated inversion recovery(FLAIR) and LSCFM images,respectively.Heterogeneous mural enhancement was found in 6 mice(4 in group 1;2 in group 2).No visible mural enhancement was observed in the other mice.LSCFM imaging revealed linear fluorescence deposition along the colorectal mucosa in all groups.Nine intraluminal masses and one prolapsed mass were detected by MR imaging with different enhancement modes and pathologies.Interstitial FITC deposition was identified where obvious enhancement was observed in FLAIR images.Bladder imaging agent accumulations were observed in 11 of 16 DMH-treated mice of groups 1 and 2.CONCLUSION:There are significant differences in colorectal uptake and distribution of SLNs between normal and DMH-treated mice,which may provide a new mechanism of contrast for MR colonography.

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.

Multi-methodological Approach to Evaluate Performances of Mucoadhesive Oral Gel Based on Nanoparticles

Oral mucositis due to chemotherapy and irradiation continues to be an important clinical problem. The effectiveness of hyaluronic acid-based compounds in accelerated healing and helping manage pain in patients with oral mucositis was demonstrated. It was investigated a protective and regenerative effect of hyaluronic acid based gel formulation enriched with NAG （N-acetyl glucosamine） loaded solid lipid nanoparticles against degenerative process of the oral mucosa. Gel formulations were obtained by adding sHA （sodium hyaluronate） into SLN aqueous suspension. Gel performances were evaluated by multi-methodological approach： mucoadhesive and barrier properties evaluation, cell viability. It was shown that gel formulation based sHA, enriched with NAG loaded SLNs, when added as suspension, demonstrated to have a good mucoadhesion profile comparable in terms of tensile work and fracture strength to Carbomer 934 2%. The presence of NAG encapsulated and not in gel formulation enhances also the biocompatibility of the system, demonstrating also to have a proliferative effect. Finally, any barrier property was altered. Finally, results demonstrated that sHA based gel formulation enriched SLNs, demonstrated good mucoadeshion property, comparable to carbopol gel, positive control. The proposed gel formulation enriched with SLNs setting up in this work could be used as innovation strategy to treat oral mucositis.

Research progress of triptolide-loaded nanoparticles delivery systems

This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.

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。

口服水飞蓟素固体脂质纳米粒（SM-SLN）肝靶向性的动物实验研究

采用冷却-匀质法制备了平均粒径为170nm的水飞蓟素固体脂质纳米粒(SM-SLN),用其给小鼠灌胃后,采用高效液相法(HPLC)测定小鼠血浆和各脏器中的药物浓度,以相对摄取率(re)、靶向效率(te)和峰浓度比(Ce)三个指标定量地评价了SM-SLN的肝靶向性.结果表明,SM-SLN组中的肝脏相对于血浆和其它脏器的te值均大于1,且肝脏中的re值(7.50)、Ce值(8.12)均为最大值,说明SM-SLN具有良好的肝靶向性.SLN可以作为治疗肝脏疾病药物的良好肝靶向载体.