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.

Surface modified solid lipid microparticles based on homolipids and Softisan 142:preliminary characterization

ObjectiveTo preliminarily investigate three different lipid matrices consisting of two natural homolipids from Capra hircus (goat fat) and Bovine Spp. (tallow fat) and one semi-synthetic lipid (Softisan? 142) separately structured with Phospholipon? 90G (P90G) as potential delivery systems for poorly water soluble drugs.MethodsThe structured lipid matrices were characterized by differential scanning calorimetry (DSC) and employed to prepare solid lipid microparticles (SLMs) by the melt homogenization method using gradient concentrations of polysorbate 80 and at different emulsification times of 2, 5 and 10 min using a Silverson mixer. The SLMs were analyzed for morphology and particle size, thermal properties, stability studies and determination of injectability.ResultsThe results showed that SLM production was optimum at 5 % of lipid matrices, 1.5 % of polysorbate 80 and emulsification time of 5 min. Increase in polysorbate 80 concentrations decreased the particle size of the SLMs. The SLMs were well formed, spherical, smooth and non-porous with particle sizes in the ranges of (13.90 ± 2.10) μm - (0.09 ± 0.01) μm for SLMs produced from the structured - tallow fat; (13.40 ± 1.30) μm - (0.10 ± 0.01) μm for the structured - goat fat and (13.40±2.00) μm - (2.10± 1.00)μm for the structured Softisan? 142 lipid matrices. DSC traces showed that Softisan? 142 was the most crystalline of all three bulk matrices due to its high enthalpy (?7.962 mW/mg) while tallow fat was the least (?5.067 mW/mg) but addition of P90G to the matrices lowered their enthalpies mostly in the structured goat fat matrices. The SLMs when stored at 4-6 ° were most stable and syringeable with 27 G needle.ConclusionsThis suggests that structured goat fat matrices with the enthalpy of ?2.813 mW/mg will mostly favour drug loading of some poorly soluble drugs more than tallow fat (?4.892 mW/mg) and Softisan? 142 (?5.501 mW/mg).

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.

Preparation and Crystal Modification of Ibuprofen-Loaded Solid Lipid Microparticles

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.

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.

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.

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 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.

Solid lipid microparticles:An approach for improving oral bioavailability of aspirin

The objectives of the work were to develop a lipid based delivery system for aspirin and to evaluate its physicochemical and pharmacodynamic properties.Aspirin-loaded solid lipid microparticles(SLMs)were formulated by hot homogenization and analysed for their encapsulation efficiency(EE%),in vitro release,particle size,anti-inflammatory and ulcer inhibition properties.Particle size ranged from 33.10±5.85 to 43.50±7.27μm for batches A1 to A3 SLMs loaded with 1,3 and 5%aspirin and containing Poloxamer 407,while batches B1,B2 and B3 formulated with Soluplus as surfactant had particle size range of 31.10±1.46 to 45.60±2.92μm.Batches A1 and B1 containing 1%of aspirin had the highest EE of 70 and 72%respectively.Maximum in vitro release of 95.1 and 93.2%were obtained at 8 h from batches A1 and B1 respectively.SLMs exhibited about 77.8%oedema inhibition,while the reference had 66.7%and ulcer inhibition range of 25-75%.Aspirin-loaded SLMs exhibited good properties and could be used orally twice daily for the treatment of inflammation.

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.

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.

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.

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.

Preparation and characterization of oleanolic acid-loaded solid lipid nanoparticles for oral administration

Oleanolic acid-loaded solid lipid nanoparticles（OA-SLNs）were prepared by using an improved emulsion-solvent evaporation method.The size,zeta potential,encapsulation efficiency,and loading efficiency of OA-SLNs were（104.5±11.7）nm, （-25.5±1.8）mV,（94.2±3.9）%,and（4.71±0.15）%,respectively.The morphology was illustrated by TEM as sphere stuffed particles.The XRD and DSC spectra confirmed that the OA molecules were dispersed uniformly into SLN matrixes.The results of in vitro release test suggested that OA was released slowly at a rate of 4.88%per hour from SLN preparation,which was consistent with the Zero-order Released Model.In addition,OA-SLNs were stable in artificial gastric juice and artificial intestinal juice.Together,our results provided new data for the potential application of OA-SLNs in oral administration.

Preparation and characterization of budesonide-loaded solid lipid nanoparticles for pulmonary delivery

To increase the solubility and adsorption of budesonide（BUD）,budesonide-loaded solid lipid nanoparticles（BUD-SLNs） were prepared and characterized in this study.Glycerin monostearate（GMS）was selected to be the matrix lipid material after calculation the differences of partial solubility parameters.An emulsification-ultrasound diffusion method was employed and formula was optimized in the BUD-SLNs preparation.The entrapment efficiency（ee%）of BUD-SLNs was（97.77±2.60）%, and the mean particle size was 147.3 nm（PDI=0.228）.Uniform and sphere particles were observed under TEM.The in vitro release of BUD-SLNs could be well explained by the biphasic release dynamics equation.The spectrums of DSC and X-ray diffraction indicated that BUD molecules were dispersed mainly into the lipids to form homogeneous matrix structure.Our results provide fundamental data for the application of SLNs in pulmonary delivery system.

Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

Impact of particle size and pH on protein corona formation of solid lipid nanoparticles:A proof-of-concept study

When nanoparticles were introduced into the biological media,the protein corona would be formed,which endowed the nanoparticles with new bio-identities.Thus,controlling protein corona formation is critical to in vivo therapeutic effect.Controlling the particle size is the most feasible method during design,and the infuence of media pH which varies with disease condition is quite important.The impact of particle size and pH on bovine serum albumin(BSA)corona formation of solid lipid nanoparticles(SLNs)was studied here.The BSA corona formation of SLNs with increasing particle size(120-480 nm)in pH 6.0 and 7.4 was investigated.Multiple techniques were employed for visualization study,conformational structure study and mechanism study,etc."BSA corona-caused aggregation"of SLN2-3 was revealed in pH 6.0 while the dispersed state of SLNs was maintained in pH 7.4,which signifcantly affected the secondary structure of BSA and cell uptake of SLNs.The main interaction was driven by van der Waals force plus hydrogen bonding in p H 7.4,while by electrostatic attraction in pH 6.0,and size-dependent adsorption was confrmed.This study provides a systematic insight to the understanding of protein corona formation of SLNs.

Solid lipid nanoparticles for nose to brain delivery of haloperidol:in vitro drug release and pharmacokinetics evaluation

In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.i.n.and HP sol.i.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.n.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

Recent advances in drug delivery applications of cubosomes,hexosomes,and solid lipid nanoparticles

The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.