Development Of Solid Lipid Nanoparticles Research Articles

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-termtherapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certainshortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. Thesolubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

Design and Development of Solid Lipid Nanoparticles of Tofacitinib Citrate for the Treatment of Rheumatoid Arthritis: A Quality by Design Approach.

Solid lipid nanoparticles, or SLNs, have gained popularity recently as a possible drug delivery method. However, the idea of using SLNs for organ and site-specific drug administration is still in its early stages due to the difficulties associated with this approach. The aim of this study is to develop SLNs with improved pharmaceutical characterization and anti-arthritic efficacy. Tofacitinib citrate (TC)-loaded SLNs were created using the microemulsification method, with the addition of stearic acid, chitosan, and Tween 80 to improve skin permeability. Seventeen SLNs were developed and characterized for particle size, entrapment efficiency (EE), and percentage drug release according to the Box-Behnken design. The DSC analysis revealed a strong endothermic peak at 166.18°C, significantly different from the pure TC reported at 218.05°C. This indicates a notable alteration in the endothermic peak of the SLNs, demonstrating a relationship with the excipients used in this investigation. XRD study highlighted significant characteristic drug peaks at positions 21.06 and 23.63 (2ɵ). These peaks represented the modifications that were seen in pure TC. The SEM analysis of the optimized lipid nanoparticles showed a smooth surface and a spherical appearance. The particle size analysis of the optimized formulation showed an average size of 181.5 nm. Also, the polydispersity index (PI) revealed a value of 0.495, indicating homogeneous dispersion. The zeta value was 8.2 mV, indicating stability.

Development of Solid Lipid Nanoparticles for Controlled Amiodarone Delivery.

In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients-Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone.

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (-) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of -0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Development of solid lipid nanoparticles of diacerein in a stable oral liquid dosage form using a central composite design

Diacerein (DCN) is used mainly to treat degenerative diseases, such as osteoarthritis. DCN is marketed commercially in solid dosage forms. Liquid formulations of diacerein (DCN) have been hindered by its poor chemical stability in aqueous media. This work aims to develop a novel, stable, oral, liquid preparation of DCN having a concentration of 50 mg/5 ml. Solid lipid nanoparticles (SLNs) of DCN were prepared using cetyl alcohol as the lipid matrix and Tween 80® as a surfactant. A quality-by-design approach was utilized to optimize DCN-SLNs. The optimum DCN-SLNs were dispersed in a structured vehicle to formulate the liquid dosage form. This liquid preparation was subjected to accelerated stability studies at 40 °C and 75% RH for 6 months. The potential of the liquid preparation to minimize the diarrheal effect of DCN was assessed. Optimum concentrations of cetyl alcohol (2%) and Tween 80® (0.9%) were chosen to obtain the desired characteristics of SLNs. Interestingly, we determined that 0.05% of citric acid was the maximum concentration that can be added to the liquid preparation of diacerein to modify its pH without compromising its stability. The results of the stability studies show that the liquid preparation was robust and it withstood storage conditions (40 °C, 75% RH) for 6 months. The encapsulation of diacerein helps to protect it from degradation and significantly reduced the occurrence of diarrhea as a side effect (p < 0.0001). Liquid preparations of DCN-SLNs can thus be marketed as a new dosage form.

Dacarbazine-encapsulated solid lipid nanoparticles for skin cancer: physical characterization, stability, in-vivo activity, histopathology, and immunohistochemistry.

This study examined the use of solid lipid nanoparticles (SLNs) to administer Dacarbazine (DTIC) to skin melanoma cells with minimal adverse effects. Melanoma is a tricky skin cancer to cure, and standard chemotherapy has many negative effects. Encapsulating DTIC in SLNs may allow the drug to target melanoma cells without harming healthy cells. The study developed and tested DTIC-loaded SLNs for skin melanoma treatment. This study encapsulated Dacarbazine (DTIC) in solid lipid nanoparticles (SLNs). SLNs with reversed micelles were produced utilizing specified ratios of the surfactant Kolliphor® P188 and phosphatidylcholine. To track SLN drug localisation, gold nanoparticles were conjugated to the DTIC. Nanoparticle size and form were examined using DLS and TEM. These approaches ensured SLNs had the correct size and shape for drug delivery. In the study, various parameters of the developed solid lipid nanoparticles (SLNs) were evaluated, including particle size, zeta potential, polydispersity index (PDI), entrapment efficacy, and cumulative drug permeation. The values for these parameters varied across the different formulations, with particle size ranging from 146 ± 4.71 nm to 715 ± 7.36 nm, zeta potential from -12.45 ± 2.78 mV to -30.78 ± 2.83 mV, PDI from 0.17 ± 0.013 to 0.51 ± 0.023, entrapment efficacy from 37.78 ± 2.78% to 87.45 ± 4.78%, and cumulative drug permeation from 117 ± 4.77 μg/cm2 to 275 ± 5.67 μg/cm2. To determine the optimal anti-cancer formulation, the DTIC-SLNs-8 nanoparticles were mixed with an optimized concentration of Gellan gum (0.01% w/v) and applied to DMBA-induced skin tumors in rats for six weeks, twice daily. Histopathology demonstrated that DTIC-SLNs-8-treated rats had less keratosis, inflammatory responses, and angiogenesis than free DTIC-treated rats. The development of SLNs may be a promising approach for melanoma treatment due to their improved drug retention over the skin. The optimised anti-cancer formulation DTIC-SLNs-8 showed improved efficacy with minimal side effects as compared to free DTIC.

Development of Solid Lipid Nanoparticles as Dry Powder: Characterization and Formulation Considerations.

Solid lipid nanoparticles (SLNs) are lipid-based colloidal systems used for the delivery of active compounds. Although SLNs have many benefits, they show important issues due to physical and chemical instability phenomena during storage. For these reasons, it is highly desirable to have a dried SLN formulation available. Therefore, the aim of the project was to identify suitable methods to obtain a dry powder formulation from an SLN suspension. The nanoparticle suspension was dried using both freeze- and spray-drying techniques. The suitability of these methods in obtaining SLN dry powders was evaluated from the analyses of nanotechnological parameters, system morphology and thermal behavior using differential scanning calorimetry. Results pointed out that both drying techniques, although at different yields, were able to produce an SLN dry powder suitable for pharmaceutical applications. Noteworthily, the freeze-drying of SLNs under optimized conditions led to a dry powder endowed with good reconstitution properties and technological parameters similar to the starting conditions. Moreover, freeze-thaw cycles were carried out as a pretest to study the protective effect of different cryoprotectants (e.g., glucose and mannitol with a concentration ranging from 1% to 10% w/v). Glucose proved to be the most effective in preventing particle growth during freezing, thawing, and freeze-drying processes; in particular, the optimum concentration of glucose was 1% w/v.

Development of Solid Lipid Nanoparticles with Letrozole for Breast Cancer Treatment: in-vitro and in-vivo evaluation

Breast cancer (BC) is the most common cancer in women worldwide. Letrozole (LTZ) is a third-generation selective nonsteroidal aromatase inhibitor and one of many anticancer drugs. Conventional LTZ therapies for BC are often administered orally or parenterally and frequently result in severe systemic side effects. To improve this situation, efforts have been made for an advanced drug delivery system that accurately releases the drug at the target site and increases therapeutic efficacy with minimal side effects. Here, we report the delivery system based on poloxomer 188 as a platform for LTZ-based solid lipid nanoparticles (SLNs) in cancer cells. The particle size, PDI, ZP, and DEE % of optimally selected LTZ -SLNs (pH 7.4) were 82.16 ± 7.24 nm, 0.287 ± 0.05, -15.0 ± 8.83 mV, and 57.89 ± 1.22 %, respectively. The SEM of LTZ -SLNs shows hexagonal phase stacking with a nanoflock morphology. The TEM image clearly shows that the introduced LTZ -SLN drugs contain LTZ drugs inside the particles. After 48 hours, it was reported that the percentage of LTZ release was 82.34%. LTZ-SLNs showed significant cytotoxic properties with an IC50 of 2.22ug/ml. The results of histopatholgical study confirmed that LTZ-SLNs can minimize the cytotoxicity of LTZ. Overall, the prepared nanoformulation offers great potential for BC treatment.

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.

Transdermal Anti-Inflammatory Delivery for Solid Lipid Nanoparticles of Ketoprofen by Microwave-Assisted Microemulsion.

To prepare solid lipid nanopaticles (SLNs) of Ketoprofen (KP) using microwave method. Ketoprofen (KP) is 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic property. The drug has short half-life of 120 mins. It belongs to BCS Class II drug. Gastric irritation is a major limitation for delivery because of acidic nature of the drug. Development of solid lipid nanoparticles with its transdermal drug delivery was the aim of present work. Microwave-assisted microemulsion technique was used for the development of solid lipid nanoparticles. Stearic acid was used as lipid and tween 80 was used as surfactant. By varying the type of lipid and input energy watt, batches were formulated. SLNs were evaluated for zeta potential, drug entrapment, particle size and in-vitro drug release. Crystallinity behaviour was determined by differential scanning calorimetry and powder X-ray diffraction. Anti-inflammatory activity was evaluated for batch M4 of SLNs. The gel was prepared for M4 batch. It was evaluated for viscosity, pH, drug content, in-vitro and ex-vivo diffusion study. SLN were developed successfully. Based on the size, entrapment efficiency, stability and drug release, batch M4 was selected. SLNs showed 74.8% entrapment efficiency. Forty-fold improvement was observed in the solubility. The particle size was of 682.9 nm and average size of 1047 nm. PDI was 0.685. Zeta potential was -29.5 mV. M4 SLNs batch of gel showed burst release followed by a controlled release for 8 hrs in in-vitro drug release. SLNs were successfully prepared by Microwave-assisted microemulsion technique. SLNs with anti-inflammatory activity was successfully developed with its transdermal delivery.

Development of Solid Lipid Nanoparticles with Letrozole for Breast Cancer Treatment: in-vitro and in-vivo evaluation

Development of Solid Lipid Nanoparticles with Letrozole for Breast Cancer Treatment: in-vitro and in-vivo evaluation

Development of solid lipid nanoparticle and nanostructured lipid carrier with dairy ingredients

Lipid nanoparticles (LN) using dairy ingredients were developed to evaluate the effect of the unsaturation degree of lipid matrix and the type of emulsifier on the physical properties, and on the kinetic stability of nanosystems over 90 days of storage. The lipid bases used were fully hydrogenated anhydrous milk fat (FHAMF); blends of FHAMF with anhydrous milk fat; and blends of FHAMF with high oleic sunflower oil. The LN were subjected to high pressure hot homogenisation. The systems with the smallest diameter were NL, whose lipid phase is composed only of FHAMF. The increased unsaturation degree of the lipid phases incorporated in the LN promoted a significant increase in particle size. The lipid nanoparticle dispersions stabilised with caseinate showed greater stability at all times evaluated. In this study, it was possible to obtain LN produced exclusively with dairy ingredients.

Development and Characterization of Stingless Bee Propolis Properties for the Development of Solid Lipid Nanoparticles for Loading Lipophilic Substances.

Stingless bees are insects which are popularly bred by agriculturists in the eastern region of Thailand for the pollination of their orchards. The products from stingless bee breeding include bee honey and bee propolis. The objective of this experiment is to study the possibility of developing stingless bee propolis wax into solid lipid nanoparticles (SLN) by the comparison of five surfactants (Brij 721, Cremophor WO 7, Myrj 52, Poloxamer 188, and Tween 80). Each surfactant is used at three concentrations: 10%, 20%, and 30%. A master formula is selected according to the following: physical features, particle size, zeta potential, and entrapment. The results showed that Brij 721 and Myri 52 at 20% can be used in preparing SLN and have good preservation properties for vitamin E (size: 451.2 nm and 416.8 nm, zeta potential: - 24.0 and - 32.7; % EE: 92.32% and 92.00%, resp.). Therefore, they are further developed by adding the following drugs at low solubility: curcumin, ibuprofen, and astaxanthin. It is found that a formula using the surfactants Brij 721 and Myrj 52 at 20% have similar drug entrapment. The entrapment study involves curcumin 82%, ibuprofen 40%, and astaxanthin 67%. Moreover, the cytotoxicity test of blank solid lipid nanoparticle found no toxicty in fibroblast cell line (CRL-2522). Therefore, from this study, it is determined that stingless bee propolis wax has the potential to be developed to provide more efficient SLN in the future.

A concise review on preparation methods used for the development of solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) are in submicron size range nanoparticles and are made of biocompatible and biodegradable materials (mainly composed of lipids and surfactants) capable of incorporating both lipophilic and hydrophilic drugs. SLNs are also considered as substitute to other colloidal drug systems, also used as controlled systems and targeted delivery. SLNs can be considered as an alternative for oral drug delivery vehicle to improve the oral bioavailability of drugs, associated reduction of drug toxicity and stability of drug in both GIT and plasma. There are different techniques used for the preparation of SLNs. Generally, the preparation of SLNs and any other nanoparticle system necessitates a dispersed system as precursor; otherwise particles are produced through the use of a particular instrumentation. This review provides the summary on the techniques or methods used for the development of SLNs of poorly water soluble drugs for improved drug delivery.&#x0D; Keywords: Solid lipid nanoparticles, controlled delivery, precursor, techniques.

Design and development of solid lipid nanoparticles of tazarotene for the treatment of psoriasis and acne: a quality by design approach

ABSTRACT Tazarotene is a third-generation retinoid applied topically for the treatment of psoriasis and acne. But its applications are limited due to its poor solubility and bioavailability. The current investigation aimed at the development of solid lipid nanoparticles (SLN) of Tazarotene for effective topical delivery. Depending on the solubility, stability, and compatibility lipids and surfactants were selected and further optimised. SLN of Tazarotene was developed by hot-homogenisation followed by probe sonication method. Preformulation studies were carried out and compatibility was confirmed with FTIR. The design of the expert, Box Behnken model was implemented and the surface response curve was plotted. Glyceryl monostearate was found to be the best lipid and a combination of tween-span as a surfactant for SLNs. The entrapment efficiency was found as 59% and the particle size of 470 nm was reported. The optimised batch showed the zeta potential of −10.3 Mv with a drug release of 59% to 77% after 6 h.

Development of solid lipid nanoparticle as carrier of pioglitazone for amplification of oral efficacy: Formulation design optimization, in-vitro characterization and in-vivo biological evaluation

Pioglitazone (PGL) is a hypoglycemic therapeutic agent used in the treatment of diabetes (type 2). The present research work was designed to prepare and optimize PGL loaded solid lipid nanoparticles (SLNs). The formulation was optimized using three factors lipid (Compritol® 888 ATO - A), surfactant (tween80- B) and homogenization speed (C), and their effects were evaluated on particle size (Y1in nm) and encapsulation efficiency (Y2in %). The optimized formulation (PGL-SLNopt) was further evaluated for physicochemical characterization, drug release, stability study, in–vivo antidiabetic and biochemical study. The optimized formulation PGL-SLNopt prepared with the composition of Compritol® 888 ATO (4.5% w/v), tween 80 (3.0% w/v) and homogenization speed (3800 rpm). The PGL-SLNopt hasshown particle size, EE, PDI, and zeta-potential 180.65 nm, 85.34%, 0.231 and −30.7 mV, respectively. The DSC and XRD spectra did not showed any peak of PGL confirm the complete entrapment of PGL in lipid due to solubilization. PGL-SLNopt exhibited significant (P < 0.05) prolonged release (89.56 ± 3.11% in 12 h) than pure PGL. The anti-diabetic study indicated that PGL-SLNopt showed significantly (P < 0.05) higher hypoglycemic activity (57.6% reduction in 12 h) as well as improved biochemical parameters. Our finding results revealed that PGL-SLNs could be a potential delivery system for the management of diabetes (type-2).

Study of pre-formulation and development of solid lipid nanoparticles containing perillyl alcohol

The aim of this work was to study the physicochemical characterization of lipid matrices composed of cetyl palmitate (CP)/perillyl alcohol (PA) and develop preliminary studies of SLN for potential application in cancer treatment. The pre-formulation was submitted to recrystallization process (heating–cooling) in a concentration of CP/AP (F1 1:0; F2 1:9; F3 1:3; and F4 1:1). The characterization showed TG presents a single stage of thermal decomposition for AP, F1, F2 and F3 and two stages for F4. DSC decrease of the onset temperature of CP before and after thermal decomposition in all samples indicates a reduction in crystallinity, and WAXD data confirmed DSC results, showing a reduction in the intensity of main diffraction peaks of the lipid mixtures and a presence of the amorphous portion in 2θ angles of 21.51° and 23.62°. Results showed the binary mixtures presented a amorphous portion facilitates AP incorporation in SLN satisfactory size, polydispersity index, zeta potential and morphology was obtained.

Development of Solid Lipid Nanoparticles by Cold Dilution of Microemulsions: Curcumin Loading, Preliminary In Vitro Studies, and Biodistribution.

Background: Solid lipid nanoparticles (SLNs) are attractive drug delivery systems for lipophilic molecules like curcumin (CURC) with low chemical stability. Methods: A simple, innovative, and cold-operating method, named “cold dilution of microemulsion” is developed by the authors to produce SLNs. An oil-in-water microemulsion (µE), whose disperse phase consisted of a solution of trilaurin in a partially water-miscible solvent, was prepared after mutually saturating solvent and water. Trilaurin SLNs precipitated following solvent removal upon water dilution of the µE. After SLN characterization (mean size, Zeta potential, CURC entrapment efficiency, and over time stability), they were tested for in vitro cytotoxicity studies on pancreatic adenocarcinoma cell lines and for in vivo preliminary biodistribution studies in Wistar healthy rats. Results: CURC loaded SLNs (SLN-CURC) had mean diameters around 200 nm, were negatively charged, stable over time, and able to entrap CURC up to almost 90%, consequently improving its stability. SLN-CURC inhibited in vitro pancreatic carcinoma cell growth in concentration-dependent manner. Their in vivo intravenous administration suggested a possible long circulation. Conclusions: These results, according to a concomitant study on chitosan-coated SLNs, confirm the possibility to apply the developed SLN-based delivery systems as a means to entrap CURC, to improve both its water dispersibility and chemical stability, facilitating its application in therapy.

Drug-Lipid-Surfactant Miscibility for the Development of Solid Lipid Nanoparticles.

This research aimed to study the correlation between miscibility of flutamide (FLT), lipids and surfactant on the particle size of solid lipid nanoparticles (SLNs). Physical mixtures (PMs) of lipids-glyceryl monooleate (GMO), Precirol® (glyceryl palmitostearate, PRE), glyceryl monostearate (GMS), and Compritol® (glyceryl dibehenate, COM) were prepared with surfactant-Gelucire® (stearoyl polyoxyl-32 glycerides, GEL) 50/13 and 44/14. PMs were prepared in 5:2 w/w ratio (lipid:surfactant) and 2:1 w/w (Flutamide (FLT):lipids/GEL 50/13) by co-melting. Miscibility of PMs was investigated using modulated differential scanning calorimetry (MDSC). SLNs with and without drug were prepared using GEL 50/13 by the ultra-sonication method and particle size analysis was conducted. PMs of GMO, GMS, and PRE with both surfactants showed a decrease in the melting temperature, no change in melting and crystallization peak was observed with COM-GELs, indicating immiscibility. Similarly, MDSC data suggests good miscibility of FLT in GMO, GMS, and GEL 50/13 but not in PRE and COM. The particle size of drug-loaded SLNs prepared from GMO and GMS with GEL 50/13 was found to be 70.2 ± 5.4 and 92.6 ± 8.5 compared to > 200-nm particles obtained from PRE and COM. On lyophilization, an increase in particles size was observed with COM only. The particle size of SLNs with PRE and COM was prominently increased during stability studies indicating SLNs prepared with GMO and GMS are more stable due to miscibility and ability to reduce the crystallinity of FLT. The results established a good correlation between drug, lipids, and surfactants miscibility to the obtained particle size of SLNs before and after lyophilization. Graphical Abstract ᅟ.

Quality by Design approach in the development of Solid Lipid Nanoparticles of Linagliptin

Quality by Design approach in the development of Solid Lipid Nanoparticles of Linagliptin