Drug-loaded Solid Lipid Nanoparticles Research Articles

Evaluation of Drug-Loaded and Surface-Adsorbed DNase/Tween-80 Solid Lipid Nanoparticles against Staphylococcus aureus Biofilms.

The aim of this study was to explore the suitability of Tween-80 or DNase I adsorbed onto the surface of gentamicin-loaded solid lipid nanoparticles (SLNs) to disrupt Staphylococcus aureus biofilms in vitro. We hypothesized that surface-adsorbed DNase I or Tween-80 of SLNs will degrade the biofilm component, extracellular DNA (e-DNA), and extracellular matrix (ECM) of S. aureus biofilms. The SLNs loaded with drug (core) and surface-adsorbed disruptors (Tween-80 or DNase I) to deliver biofilm disruptors first at the site of action, which will help to break down the biofilm, and further drug release from the core will easily penetrate the biofilm and facilitate the killing of bacteria residing in S. aureus biofilms. The SLNs were synthesized by the double emulsion method; the size was 287.3 ± 7.4 nm for blank SLNs and 292.4 ± 2.36 nm for drug-loaded SLNs. The ζ-potential of blank SLNs was -25.6 ± 0.26 mV and that of drug-loaded SLNs was -13.16 ± 0.51 mV, respectively. The successful adsorption of DNase I or Tween-80 was confirmed by the activity of DNase I in blank surface-adsorbed SLNs and the change in the ζ-potential of SLNs after adsorbing DNase I or Tween-80. The surface morphology and size of the SLNs were further characterized using scanning electron microscopy. The encapsulation efficiency of the drug was 16.85 ± 0.84%. The compatibility of the drug with the excipient was confirmed by Fourier transform infrared spectroscopy and the degree of crystallinity was confirmed by X-ray diffraction (XRD) analysis. SLNs showed a sustained release of the drug up to 360 h. SLNs were easily taken up by A549 cells with minimal or no toxicity. The present study showed that Tween-80- or DNase I-adsorbed SLNs efficiently disrupt S. aureus biofilms and possess no or minimal toxicity against cells and red blood cells (RBCs).

GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting

The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.

A Recent Review on Bio-availability Enhancement of Poorly Water-soluble Drugs by using Bioenhancer and Nanoparticulate Drug Delivery System.

Intravenous route of drug administration has maximum bioavailability, which shows 100% of the drug reaches blood circulation, whereas the oral administration of drugs, are readily undergoing pre-systemic metabolism, which means the poor bioavailability of the drug and limited amount of drug reaches the target site. Bioenhancers are substances having medicinal entities which enhance the bioavailability and efficacy of the active constituents of drugs. The enhanced bioavailability of drugs may lead to dose reduction, which may further reduce the cost and undesired side effects associated with the drugs. The solid lipid nanoparticles (SLNs) loaded with ketoprofen made from carnauba wax and beeswax. It was discovered that when the drug-loaded SLNs were mixed with egg-lecithin and Tween-80, as well as when the total surfactant concentration was increased, the average particle size of the drug-loaded SLNs decreased. The drug-loaded nanoparticles, when given in combination with bio-enhancers such as piperine and quercetin, enhanced the drug's effectiveness. The Area Under Curve (AUC) was increased when the drug was coupled with bio-enhancers. Based on the findings, it can be concluded that piperine and quercetin when used with drug-loaded nanoparticles improve their therapeutic effectiveness. Bioenhancers are crucial to amplifying the bioavailability of many synthetic drugs. These attributes are useful to reduce the dose of drugs and increase the therapeutic efficacy of drugs with poor bioavailability.

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models.

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs’ suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.

Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment.

In the present work, an attempt was undertaken to improve the oral bioavailability and anticancer activity of abiraterone acetate. Solid lipid nanoparticles (SLNs) were developed using the quality by design (QbD) principles and evaluated through in vitro, ex vivo, and in vivo studies. Solid lipid suitability was evaluated by equilibrium solubility study, while surfactant and cosurfactant were screened based on the ability to form microemulsion with the selected lipid. SLNs were prepared by emulsion/solvent evaporation method using glyceryl monostearate, Tween 80, and Poloxamer 407 as the solid lipid, surfactant, and cosurfactant, respectively. Box-Behnken design was applied for optimization of material attributes and evaluating their impact on particle size, polydispersity index, zeta potential, and entrapment efficiency of the SLNs. In vitro drug release study was evaluated in simulated gastric and intestinal fluids. Cell culture studies on PC-3 cells were performed to evaluate the cytotoxicity of the drug-loaded SLNs in comparison to the free drug suspension. Qualitative uptake was evaluated for Rhodamine B-loaded SLNs and compared with free dye solution. Ex vivo permeability was evaluated on Wistar rat intestine and in vivo pharmacokinetic evaluation on Wistar rats for SLNs and free drug suspension. Concisely, the SLNs showed potential for significant improvement in the biopharmaceutical performance of the selected drug candidate over the existing formulations of abiraterone acetate.

Stability mechanisms for microwave-produced solid lipid nanoparticles

Tween® 20 stabilised stearic acid solid lipid nanoparticles (SLNs) were prepared using a one-pot microwave-assisted microemulsion technique. Two model water-insoluble drugs, the carboxylic acid-based indomethacin, and the imidazole-based miconazole nitrate, were then used to load the SLNs, and their subsequent physical properties (particle size and zeta potential) were measured and used to predict dispersion stability.Drug-free SLNs had a particle size of 239 nm and a zeta potential of − 29 mV. Indomethacin-loaded SLNs had a particle size of 266 nm and zeta potential of − 30 mV. Miconazole-loaded SLNs had a particle size of 266 nm and zeta potential of + 15 mV. These values were found to be relatively stable (under mildly acidic conditions) and recommend the suitability of the SLNs as a drug carrier.In all cases, the particle size and zeta potential were shown to be pH-dependent. For particle size, a minimum value was obtained at approximately pH 5, which corresponds to the pKa of the lipid used (stearic acid) indicating stearic acid adsorption onto the surface is likely to be at least partly responsible for dispersion stability. We conclude that dispersion stability arises from a combination of electrostatic stability (from adsorbed stearic acid) and limited steric stability from non-ionic (Tween® 20) surface-associated micelles.Dispersions were found to be unstable under alkaline conditions despite the increasingly negative zeta potential of all dispersions. This was observed as an increasingly larger particle size at pH > 7 combined with the observation that particle sizes at pH > 7 were also unstable and continued to increase with time. Visual observations showed dispersions physically broke within a few days at pH values > 7.The encapsulation efficiency (EE) and loading capacity (LC) of drug-loaded SLNs were shown to be close to their theoretical maximum (100%) at low pH, but decreased to < 20%, in the case of indomethacin-loaded SLNs, at a pH >> 7. Interestingly, the EE and LC of miconazole-loaded SLNs when first formed were relatively unaffected by pH. pH control, therefore, is very important to particle stability, and the pH should be kept neutral to mildly acidic.

Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study.

Curcumin is well known for its neuroprotective effect, and also able to alleviate Parkinsonian features. Clinical application of curcumin is limited due to its low bioavailability. Hence, we hypothesized that the microneedles (MN) containing drug-loaded solid lipid nanoparticles (SLNs) may be able to improve its bioavailability and efficacy. The SLNs were prepared with microemulsion technique using glyceryl monostearate as a lipid and tween 80 as a stabilizer. The particle size, polydispersity index, zeta potential, and entrapment efficiency of prepared SLNs were determined. The optimized formulation was incorporated into microneedle arrays using micromolding technique and fabricated microneedle patch were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, optical microscopy, ex vivo permeation studies, histology studies, and fluorescent microscopy. The fabricated microneedle patch was also evaluated for neuroprotective activity and skin irritation potential. Fourier transform infrared spectroscopy studies of SLNs and microneedles confirmed the chemical compatibility of excipients with curcumin. The developed microneedles were also found to be non-irritant with decreased degree of bradykinesia, high motor coordination, and balance ability. The study provided a theoretical basis for the use of novel microneedle containing curcumin-loaded solid lipid nanoparticles as a useful tool for the treatment of Parkinson's disease.

Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics for the treatment of psoriasis

ABSTRACT Introduction Psoriasis is an auto-immune inflammatory skin disease affecting people worldwide. Its topical therapy via different nanoformulations prevents the long-term side-effects of conventional formulations. Nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), pose extra benefits in topical drug delivery due to their lipid constituents. Although both natural and synthetic anti-psoriatic drugs have been successfully incorporated in these nanoformulations, yet further studies including dual drug-loadings are being carried out for assessing their efficacy. Areas covered This review aims at describing the different aspects of SLNs and NLCs in psoriasis, including their skin permeation behavior and the various drug molecules incorporated. The recent studies with single- and dual drug-loaded SLNs and NLCs have also been discussed in the review. Expert opinion SLNs and NLCs have been very effective in mitigating psoriasis when compared to commercial formulations. They have also shown promising results when loaded with two drugs, thus overcoming drawbacks of traditional combination therapy. Therefore, various drug/antibody/siRNA combinations can be selected in the upcoming research works to evaluate their synergistic performance against psoriasis. However, the conclusions drawn so far are only based on the pre-clinical studies and hence further investigations are required to obtain their clinical trial outcomes.

Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB.

The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

Brain-targeted, drug-loaded solid lipid nanoparticles against glioblastoma cells in culture

The aim of this study was the preparation of solid lipid nanoparticles (SLN) formed from cetyl palmitate with having targeting molecules for monocarboxylate transporter-1 (MCT-1): β-hydroxybutyric acid and anticancer agents: carmustine (BCNU) and temozolomide (TMZ) for enhanced anti-proliferation against glioblastoma multiforme (GBM). Properties including size, morphology, chemical structure, zeta potential, drug encapsulation efficacy, drug release, biocompatibility, stability were determined, and in vitro studies were done. BCNU and TMZ loaded SLNs had a hydrodynamic size of 227 nm ± 46 a zeta potential of −25 mV ± 4 with biocompatible features. The data showed rapid drug release at first and then continuous release. Nanoparticles could be stored for nine months. BCNU and TMZ loaded SLNs exhibited a remarkable increment in the antitumor activity compared to the free-drugs and induced apoptosis on U87MG cells. In addition, targeted nanoparticles were more uptaken by MCT-1 expressing brain cells. This study indicated that BCNU and TMZ loaded SLNs could act as a useful anticancer system for targeted GBM therapy.

A study to enhance the oral bioavailability of s-adenosyl-l-methionine (SAMe): SLN and SLN nanocomposite particles

The endogenous molecule, S-adenosyl-l-methionine (SAMe) is a key factor due to its role in the methylation cycle and modulation of monoaminergic neurotransmission. Since many mental disorders have linked to the monoaminergic system, the level of SAMe in blood and cerebrospinal fluid is important in the treatment of major depression. In this study, solid lipid nanoparticles (SLN) were prepared in order to increase the limited oral bioavailability of SAMe, and SLN based nanocomposite particles (SAMe-SLN-NC) were further developed using an enteric polymer for passive targeting of intestinal lymphatic system. In this manner, it was also aimed to protect SAMe loaded SLN from harsh gastric environment as well as hepatic first-pass metabolism. Dynamic light scattering (DLS) analysis of SLN was performed, drug content was measured, SAMe release patterns were examined and the permeation ability of SAMe was investigated by the Parallel Artificial Membrane Permeability Assay (PAMPA) to characterize SAMe loaded SLN formulation. According to the PAMPA results, SAMe-SLN with the average particle size of 242 nm showed enhanced SAMe permeability in comparison to pure drug. Delayed drug release obtained by SLN nanocomposite particles indicated the protection of drug-loaded SLN in the acidic gastric medium and their intact presence in the intestine. SAMe solution or particle suspensions were prepared using 0.45 (w/v) hydroxypropyl methylcellulose aqueous solution to be applied to groups of animals for pharmacokinetic studies. In vivo pharmacokinetic parameters revealed enhancement in relative bioavailability of SAMe upon oral administration of SLN based formulations. This was attributed to intact absorption of lipid matrix through lymphatic path. A statistically significant increase in SAMe plasma levels was obtained at 15th and 30th minutes with SAMe-SLN and at 2nd and 4th hours with SAMe-SLN-NC.Overall results suggest that SLN is a promising carrier to passive lymphatic targeting of SAMe and novel SLN nanocomposite particles which presented efficient oral bioavailability is a potential way for oral delivery of SAMe and treatment of major depression.

An experimental and computational study to evaluation of chitosan/gum tragacanth coated-natural lipid-based nanocarriers for sunitinib delivery

This study aimed to introduce two natural lipids including the fat tail (FT) and the local oil (Roghan Kermanshahi) in order to design lipid nanocarriers for loading of sunitinib malate as a poorly water-soluble anticancer drug. The drug-loaded solid lipid nanoparticles (SLNs) were fabricated using the modified solvent evaporation-ultrasonic combination method. Coating with chitosan and gum tragacanth (GT) was performed. The physicochemical properties of nanoparticles were analyzed by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC) and scanning electron microscopy (SEM). Also, in vitro drug release and cytotoxicity effect was investigated. Furthermore, the atomic details of SLNs formation and drug encapsulation were investigated by the computational study. The results showed that polymer-FT-SLNs and polymer-Roghan-SLNs had the particle size in the nanometer range (below 150 nm) with the zeta potential values of higher than |−28 mV| and possessed high entrapment efficiency and loading content of sunitinib. The release of drugs from as prepared delivery systems has demonstrated a sustained release pattern, which was fitted to Higuchi’s kinetics. Prepared free SLNs had shown no cytotoxicity effect while sunitinib loaded SLNs had suitable cytotoxicity against acute myeloid leukemia cells (THP-1). The computational approach has demonstrated that the drug-lipid binding energies are higher in the FT system than RK. Our results indicated that the as-prepared chitosan/tragacanth encapsulated natural lipid SLNs can be a good drug nanocarrier for the hydrophobic anticancer drug.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Paclitaxel and naringenin-loaded solid lipid nanoparticles surface modified with cyclic peptides with improved tumor targeting ability in glioblastoma multiforme

The present work describes the systematic development of paclitaxel and naringenin-loaded solid lipid nanoparticles (SLNs) for the treatment of glioblastoma multiforme (GBM). So far only temozolomide therapy is available for the GBM treatment, which fails by large amount due to poor brain permeability of the drug and recurrent metastasis of the tumor. Thus, we investigated the drug combination containing paclitaxel and naringenin for the treatment of GBM, as these drugs have individually demonstrated significant potential for the management of a wide variety of carcinoma. A systematic product development approach was adopted where risk assessment was performed for evaluating the impact of various formulation and process parameters on the quality attributes of the SLNs. I-optimal response surface design was employed for optimization of the dual drug-loaded SLNs prepared by micro-emulsification method, where Percirol ATO5 and Dynasan 114 were used as the solid lipid and surfactant, while Lutrol F188 was used as the stabilizer. Drug loaded-SLNs were subjected to detailed in vitro and in vivo characterization studies. Cyclic RGD peptide sequence (Arg-Gly-Asp) was added to the formulation to obtain the surface modified SLNs which were also evaluated for the particle size and surface charge. The optimized drug-loaded SLNs exhibited particle size and surface charge of 129 nm and 23 mV, drug entrapment efficiency >80% and drug loading efficiency >7%. In vitro drug release study carried out by micro dialysis bag method indicated more than 70% drug was release observed within 8 h time period. In vivo pharmacokinetic evaluation showed significant improvement (p < 0.05) in drug absorption parameters (Cmax and AUC) from the optimized SLNs over the free drug suspension. Cytotoxicity evaluation on U87MG glioma cells indicated SLNs with higher cytotoxicity as compared to that of the free drug suspension (p < 0.05). Evaluation of uptake by florescence measurement indicated superior uptake of SLNs tagged with dye over the plain dye solution. Overall, the dual drug-loaded SLNs showed better chemoprotective effect over the plain drug solution, thus construed superior anticancer activity of the developed nanoformulation in the management of glioblastoma multiforme.

Lyophilized Drug-Loaded Solid Lipid Nanoparticles Formulated with Beeswax and Theobroma Oil.

Solid lipid nanoparticles (SLNs) have the potential to enhance the systemic availability of an active pharmaceutical ingredient (API) or reduce its toxicity through uptake of the SLNs from the gastrointestinal tract or controlled release of the API, respectively. In both aspects, the responses of the lipid matrix to external challenges is crucial. Here, we evaluate the effects of lyophilization on key responses of 1:1 beeswax–theobroma oil matrix SLNs using three model drugs: amphotericin B (AMB), paracetamol (PAR), and sulfasalazine (SSZ). Fresh SLNs were stable with sizes ranging between 206.5–236.9 nm. Lyophilization and storage for 24 months (4–8 °C) caused a 1.6- and 1.5-fold increase in size, respectively, in all three SLNs. Zeta potential was >60 mV in fresh, stored, and lyophilized SLNs, indicating good colloidal stability. Drug release was not significantly affected by lyophilization up to 8 h. Drug release percentages at end time were 11.8 ± 0.4, 65.9 ± 0.04, and 31.4 ± 1.95% from fresh AMB-SLNs, PAR-SLNs, and SSZ-SLNs, respectively, and 11.4 ± 0.4, 76.04 ± 0.21, and 31.6 ± 0.33% from lyophilized SLNs, respectively. Thus, rate of release is dependent on API solubility (AMB < SSZ < PAR). Drug release from each matrix followed the Higuchi model and was not affected by lyophilization. The above SLNs show potential for use in delivering hydrophilic and lipophilic drugs.

Optimization of Itroconazole Solid Lipid Nanoparticles for Topical Delivery

Introduction: The objective of this study was to formulate water-insoluble drug Itraconazole (ITZ) into Solid Lipid Nanoparticles (SLNs) for topical delivery. Methods: The drug-loaded SLNs were prepared by Microemulsion method using cholesterol (CH) and Lubritab (LU) and further characterized for different parameters like particle size, zeta potential, drug entrapment efficiency etc. The mean particle size with Lubritab SLN was in the range 155.01-161.67 nm, whereas for Cholestrol SLN it was in the range of 218.87-230.16 nm. SEM showed spherical nature of the SLNs. Results: The entrapment efficiency of SLN was found to be more for cholesterol as compared to Lubritab. The crystalline properties of drug was reduced in SLNs as evaluated by X-ray diffraction (XRD). Ex vivo study indicated the ITZ-SLN exhibited high concentration. Conclusion: The permeability of drug was studied by use of Franz-diffusion cell, and permeation of drug through Lubritab SLN (ITZ LU) was higher than that of Cholesterol SLN (ITZ CH). The formulated ITZ-SLNs exhibited clear zone.

The effect of efflux pump inhibitors on in vitro and in vivo efficacy of solid lipid nanoparticles containing SN38

7-ethyl-10-hydroxy camptothecin (SN38) is poorly soluble in water and pharmaceutical solvents. Oral administration of SN38 was restricted due to poor solubility. Many ways such as encapsulation in carriers are used for solving this restriction. Solid lipid nanoparticles (SLNs) are able to encapsulate lipophilic drugs and improve oral bioavailability. In addition, concomitant use of the efflux pump inhibitors can improve the performance of the encapsulated drug. In the present study, SN38 was loaded in SLNs. Nanoparticle size, zeta potential and drug encapsulation efficacy were investigated. The drug release from nanoparticles was also determined in the simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). Cytotoxicity of nanoparticles after 24 and 48 h were measured in C26 and Caco-2 cell lines. The cellular uptake of the drug was determined. Tumor growth inhibition and survival were evaluated in animal model. The results showed that the drug-loaded SLNs were about 172.3 ± 3.3 nm in size. The encapsulation efficacy was 61% ± 7. In cellular studies, higher toxicity of the drug-loaded nanoparticles with the two substances piperine and quercetin were achieved in the Caco-2 cell line. It was observed that drug uptake of nanoparticles containing SN38 with or without piperine and quercetin by C26 and Caco-2 cell line was significantly higher than free SN38 in 2 and 4 h. According to in vivo studies, the use of piperine and quercetin with SLN containing SN38 has produced a favorable synergistic effect as increasing the survival time in animal model.

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

The development of an effective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-β-cyclodextrin (HPCD) modified solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modified dual drug-loaded solid lipid nanoparticles (m-DDSLNs). The optimized formulations have a mean particle size of 141 ± 3.2 nm, a polydispersity index of 0.248 ± 0.11 and entrapment efficiency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confirmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profile upto 57% (AmB) and 21.5% (PM) within 72 h and were stable at both 4 °C and 25 °C during short term stability studies performed for 2 months. Confocal laser scanning microscopy confirmed complete cellular internalization of SLNs within 24 h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confirmed the safety and biocompatibility of the developed formulations. Further, m-DDSLNs did not induce any hepatic/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fluids and simulated intestinal fluids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1 µg/ml) has shown a maximum percentage of inhibition (96.22%) on intra-cellular amastigote growth of L. donovani. m-DDSLNs (20 mg/kg × 5 days, p.o.) has significantly (P < 0.01) reduced the liver parasite burden as compared to miltefosine (3 mg/kg × 5 days, p.o.) in L. donovani-infected BALB/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a promising approach towards the oral delivery of anti-leishmanial drugs.

Exploring the drug-lipid interaction of weak-hydrophobic drug loaded solid lipid nanoparticles by isothermal titration calorimetry

Drug-lipid interaction was a vital issue for weak-hydrophobic drug-loaded solid lipid nanoparticles (WHD-SLNs). With a weak drug-lipid interaction, the drug loading capacity and physical stability could be low, and thus the drug-lipid interaction should be investigated. This paper was aimed to explore the drug-lipid interactions of WHD-SLNs by isothermal titration calorimetry (ITC). Benzoic acid (BEA) and salicylic acid (SAA) were chosen as the model weak-hydrophobic drugs, and stearic acid (SA) was selected as the model lipid material. For reference, the melting point depression (the proof of molecular interaction) of BEA-SA system and SAA-SA system was explored by differential scanning calorimetry (DSC) and hot stage polarized-light microscopy (HSPM). The ITC results demonstrated that BEA-SA interaction had negative ΔH and negative ΔS, while SAA-SA interaction possessed slightly negative ΔH and positive ΔS. It was indicated that the major interactions in BEA-SA interaction and SAA-SA interaction were hydrogen bonds and hydrophobic forces, respectively. Shown by DSC and HSPM results, the melting point depression in BEA-SA system was more significant than SAA-SA system. Therefore, melting point depression was mainly associated with hydrogen bond interactions, rather than hydrophobic forces. This study could provide new insight for the interpretation of drug-lipid interaction of WHD-SLNs.

Solid lipid nanoparticles self-assembled from spray dried microparticles.

We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (IMC) and hydrophilic (5-FU) drugs. They show extended release profiles over more than 24 h, and in permeation studies the drug cargo is seen to accumulate inside cancer cells. This overcomes major issues with achieving local intestinal delivery of these active ingredients, in that IMC permeates well and thus will enter the systemic circulation and potentially lead to side effects, while 5-FU remains in the lumen of the small intestine and will be secreted without having any therapeutic benefit. The SLN formulations are as effective as the pure drugs in terms of their ability to induce cell death. Our approach represents a new and simple route to the fabrication of SLNs: by assembling these from spray-dried microparticles on demand, we can circumvent the low storage stability which plagues SLN formulations.