High Shear Homogenization Method Research Articles

Optimization of atorvastatin and quercetin-loaded solid lipid nanoparticles using Box-Behnken design.

Aim: The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. Materials & methods: SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their in vitro anticancer activity. Results: The optimized SLN exhibited narrow size distribution (PDI=0.338±0.034), a particle size of 72.5±6.5 nm, higher entrapment efficiency (<90%), sustained release and spherical surface particles. The in vitro cytotoxicity studies showed a significant reduction in IC50 values on MDA-MB-231 cell lines. Conclusion: We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer.

Sustainable fish oil extraction from catfish visceral biomass: A comparative study between high-shear homogenization and high-frequency ultrasound on wet rendering process

Traditional wet rendering leads to the degradation of polyunsaturated fatty acids in fish oil. Therefore, we combined this method with high-shear homogenization and high-frequency ultrasound to extract oil from Clarias magur visceral biomass. This way, we aimed to achieve higher oil yield, shorter extraction times, and a better preservation of polyunsaturated fatty acids. High-shear homogenization and high-frequency ultrasound increased the oil yields by 9.17 and 10.55%, respectively, compared to traditional wet rendering. The oil quality was also improved, with lower acid and peroxide values. Scanning electron microscopy confirmed enhanced cell disruption for increasing the oil extraction efficiency. Fourier transfer infrared spectroscopy also proved the efficacy of homogenization and ultrasound pretreatment in enhancing the extraction of polyunsaturated fatty acids from C. magur visceral biomass. Their content showed a significant variation among different extraction methods. Specifically, the high-frequency ultrasound method resulted in a notable 15.1% increase, while the high-shear homogenization method demonstrated a significant 13.3% increase, compared to the wet rendering method (control). The oil extracted by the high-frequency ultrasound method demonstrated a 7.5% increase in eicosatetraenoic acid and a 11.7% increase in docosahexaenoic acid, as compared to the oil obtained from the control method. High-shear homogenization and high-frequency ultrasound shortened the extraction time and reduced the temperature requirements for oil extraction from wet biomass. These techniques have potential for efficient fish oil extraction, valuable in the healthcare and food industries.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.

Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 μM for free RES to 0.5 ± 0.033 μM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 μMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 μM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions

Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (−35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell’s results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-β, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.

Nanoemulsions as a Promising Carrier for Topical Delivery of Etodolac: Formulation Development and Characterization.

This research primarily focuses on the development of innovative topical nanoemulsions for etodolac, aimed at surmounting its inherent limitations. The preparation of etodolac nanoemulsions is accomplished through a combination of high shear homogenization and ultrasonication methods. The optimization of the formulation components is systematically conducted using the design of experiments methodology. The droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) of the optimized formulation were assessed using the differential light scattering (DLS) technique. Surface morphology examinations were conducted using electron microscopy, while interactions between excipients and the drug were analyzed through FTIR analysis. Additionally, in vitro release and ex vivo permeability studies were carried out. Furthermore, anti-inflammatory activity was evaluated in the context of a carrageenan-induced paw edema model in rats. The DS, PDI, and ZP of the optimal formulation were 163.5 nm, 0.141, and -33.1 mV, respectively. The in vitro release profile was assessed as a sustained release by following a non-Fickian drug transport. The flux of etodolac nanoemulsions and coarse dispersions were 165.7 ± 11.7 µg/cm2 h and 59.7 ± 15.2 µg/cm2 h, respectively. Enhanced edema inhibition was observed at 13.4%, 36.5%, and 50.65% for the 6th, 8th, and 24th hours, respectively. Taken together, these results confirmed that nanoemulsions are promising carriers for the topical delivery of etodolac.

Preparation, Characterization, and Molecular Dynamic Simulation of Novel Coenzyme Q10 Loaded Nanostructured Lipid Carriers.

Research proved that coenzyme Q10-loaded NLC effectively removes skin wrinkles, therefore, such a formulation with good characteristics is still the research goal. This study investigated the effect of solid lipids and surfactant type on the physical characteristics of Q10-NLC. We aimed to achieve the optimum formulation for producing NLC with long-term stability and high Entrapment efficiency (E.E.) %. We compared the experimental results with the output of the Molecular dynamic (M.D.) simulations. To develop Q10-NLC, various solid lipids, MCT oil, and surfactants were employed. The formulations were prepared by high-shear homogenization and ultrasound methods. Stability studies were carried out 1,3, and 6 months at 4, 25, and 40°C. The optimized NLC formulations were characterized by photon correlation spectroscopy (PCS), Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR). E.E. % was determined by HPLC analysis. Atomistic M.D. simulations of two model systems were performed to gain insights into the self-assembled process of co-Q10 with other formulation components. Statistical analysis (Two-way ANOVA) revealed that solid lipid and surfactant factors had a significant influence on particle size, PDI, and zeta potential (***p < 0.0001). According to the results, F1 and F6 formulations had desirable surface characterizations, physicochemical stability, and high E.E. %. The atomistic M.D. simulations confirmed that the F1 system (best) was more stable than the F31 system (worst). The solid lipids: tripalmitin and compritol, stabilized with 4% tween 80 and 1% span 80, have produced stable NLC with the best surface characteristics that could be a promising formulation for the delivery of Q10. Atomistic M.D. simulation has confirmed the stability of F1 in comparison to F31.

Application of Solid Lipid Nanoparticles Method in Black Sea Cucumber (Holothuria atra) Extract Peel-off Gel Mask and Antioxidant Activity Tests

Black Sea cucumbers (Holothuria atra) are a potential source of active metabolites such as flavonoids widely used for nutraceutical, pharmaceutical, and cosmeceutical products. The type of nanoparticle that is often used in cosmetics and skin products is Solid Lipid Nanoparticles (SLN). In this study, the SLN of black sea cucumber extract will be prepared in the form of a peel-off gel mask as an antioxidant. Black sea cucumbers were extracted using the maceration method, while SLN preparation used high-shear homogenization and freeze-drying methods. Crude extract and SLN were formulated into peel-off gels and then evaluated, including organoleptic, homogeneity, viscosity, pH, spreadability, drying time, tensile strength test, and antioxidant activity using the DPPH method. The IC50 values of blank (F1), peel-off gel extract (F2), and nanoparticle peel-off gel extract (F3) were each 600.8727 ± 0.43; 580.7849±0.7; and 592.76±0.55 µg/mL. In conclusion, the SLN method can be applied to the formulation of black sea cucumber extract nanoparticles. However, peel-off gel masks from the crude and nanoparticle extracts have very weak antioxidant activity.

Development of nanostructured lipid carrier containing tea tree oil: Physicochemical properties and stability

Context: Tea tree oil (TTO) is an essential oil derived from Melaleuca alternifolia, with high antimicrobial and antifungal potential. Unfortunately, its topical antifungal efficacy is limited because it is volatile, thermolabile and easily oxidized. A formulation has been developed to overcome this problem by encapsulating TTO in a nanostructured lipid carrier (NLC). Aims: To determine the effect of the liquid to solid lipid ratio on the physicochemical properties and the stability of TTO-loaded NLC. Methods: Five formula of TTO-loaded NLCs were produced by high shear homogenization method and characterized according to their particle size, size distribution, polydispersity, zeta potential, thermal characteristics, X-ray diffraction, and terpinen-4-ol concentration. In addition, a stability study was conducted by observing its physical and chemical characteristics during storage in the refrigerator (4 ± 2°C) and at room temperature (27 ± 2°C) for six months. Results: The resulting TTO-loaded NLC had an average droplet size under 400 nm. The particle size increases with increasing amount of liquid lipid in the formula. There were insignificant changes in organoleptic properties, polydispersity index, zeta potential and terpinene-4-ol concentration during stability study for six months. However, the particle size slightly increased during the six months of storage. Furthermore, the NLC 3, which formulated with a 25:95 ratio liquid to solid lipid, was be chosen as the best formula, since it demonstrated the best physicochemical characteristic and stability. Conclusions: TTO-loaded NLC with good physicochemical characteristics and stability has been successfully developed. In addition, NLC 3 is considered as the best NLC formula, which exhibits characteristics and stability that meet the requirements.

Effect of Different Lipid Ratios on Physicochemical Stability and Drug Release of Nanostructured Lipid Carriers Loaded Coenzyme Q10

Background: For treatment or skin care via topical route, Coenzyme Q10 needs to permeate the epidermis which it is practically insoluble in water and a high molecular weight that make it difficult to penetrate the skin. Nanostructured Lipid Carriers (NLC) is chosen because of its ability to dissolve and solve the problem of low skin permeation. The type and ratio of solid and liquid lipids used in NLC affect the physicochemical characteristics, thus affecting the release profile and system stability. Objective: This study aimed to determine the effect of various ratios of Compritol 888 ATO as solid lipid and Miglyol 812 as liquid lipid on the physicochemical stability and Coenzyme Q10 release profile of NLC system. Methods: NLC was prepared using High Shear Homogenization method with three different lipid ratios. The ratio of Compritol 888 ATO : Miglyol 812 was 70:30, 80:20, and 90:10, respectively. NLC was evaluated for drug release and stability parameters including organoleptic, particle size, polydispersity index (PI), pH, viscosity, assay, and entrapment efficiency. Results: The stability test result for 90 days showed increments in the particle size and viscosity, whereas for assay and entrapment efficiency were decreased. The release test results showed no significant difference in the release parameters of the three tested formulas. Conclusion: During stability evaluation, NLC-CoQ10 systems did not significantly change pH and PI values, but statistically significantly changed particle size, viscosity, assay, and entrapment efficiency. The different in lipid ratios used in the formulas did not show significantly different results for release parameters.

Characterization and Penetration Profile of Resveratrol-Loaded Nanostructured Lipid Carrier (NLC) for Topical Anti-Aging

Skin aging is an essential factor in the degradation of skin’s structural components, which is signed by less elastic and drier, lines and wrinkles, and looks and feels like older skin. Resveratrol (RSV) is a polyphenol compound with a potent antioxidant and antiaging effect, which can be found in many plants, such as red wine, red grapes, peanuts, berries, and Japanese knotweed root. It is active in inhibiting and neutralizing the formation of ROS and synthetic radicals under in vitro conditions. RSV is an unstable to light compound and insoluble in water, which has to be protected by proper delivery systems such as Nanostructured Lipid Carrier (NLC). This study aimed to determine the characterization and penetration profile of RSV-loaded NLC (RSV-NLC) using the High Shear Homogenization (HSH) method. RSV-NLC was formulated with four different surfactant ratios (5:5; 6:6; 7:7; 8:8) and characterized for entrapment efficiency, organoleptic, viscosity, pH, zeta potential, melting temperature, crystal lattice analysis, particle morphology, particle size, and Polydispersity Index (PI), then examined for their penetration profile. The different ratios of Tween 80 and Span 20 affect the characteristics of RSV-NLC (viscosity, zeta potential, particle morphology, and entrapment efficiency) but do not affect the penetration depth of RSV in the skin. Tween 80:Span 20 (5:5) is the best combination for RSV-NLC in characterization and penetration profile.

The effect of peppermint oil addition on the physical stability, irritability, and penetration of nanostructured lipid carrier coenzyme Q10.

Coenzyme Q10 is formulated into Nanostructured Lipid Carrier (NLC) added with peppermint oil (PO) 0% (F1), 1% (F2), 1.5% (F3) and 2% (F4) to increase its penetration. This study aims to determine the effect of PO addition on the irritability, stability, and penetration of Coenzyme Q10 in the NLC. Coenzyme Q10 NLC was prepared using the High Shear Homogenization method. Furthermore, physical characterization was carried out. Physical stability testing was carried out for 90 days at a temperature of 25±5oC and an RH of 60±10%. The in vivo irritation test was observed for mice's back skin after 24 hours while the penetration study was further evaluated at 2 hours of the sample application. Increasing the PO amount into Coenzyme Q10 NLC reduced the viscosity which was 329.1±15.5 cps for PO 0% to 219.9±2.9 cps for 2% addition. The observation of particle morphology showed that all NLC Coenzyme Q10 has a spherical particle shape with particle size between 188.25±13.22 to 197.80±14.19 nm. All formulas had high entrapment efficiency (>80%). PO addition did not cause changes in physical characteristics during 90 days of storage. The 24 hours' irritation test showed that F2 and F3 are non-irritating. By PO addition skin penetration improved at 2 hours' penetration study. PO addition up to 2% reduced viscosity, but did not affect particle size and morphology of Coenzyme Q10 NLC. Addition of PO up to 1.5% increased entrapment efficiency, did not irritate and increased the penetration of Coenzyme Q10 NLC.

The activity of candlenut oil in the nanostructured lipid carrier system on hair growth in rats.

Candlenut oil (Aleurites moluccana L. Willd), which is also called Aleurites moluccana Seed (AMS) oil, is empirically effective as a hair growth agent, it is an unstable substance. Nanostructured Lipid Carrier (NLC) is a delivery system that is proven to increase the effectiveness and stability of the material, and the usage of solid lipid combination: beeswax-oleum cacao can produce good NLC characteristics. To determine the effectiveness of NLC_AMS oil with different combination of beeswax-oleum cacao (100:0; 50:50; 25:75; and 0:100) as a hair growth agent, using rats as subjects. NLC-AMS oil was made using 20% of total lipid with 5% AMS oil as liquid lipid and 15% solid lipid; combinations of beeswax-oleum cacao were of different ratios (100:0; 50:50; 25:75; and 0:100). NLC was made by High Shear Homogenization (HPH) method. Hair growth activity test carried out on male white rats using the research methods of Yoon (2010). The addition of oleum cacao as a solid lipid did not affect the pH, but increased the consistency and decreased the particle size of NLC- AMS oil. There was a relationship between the characteristic of NLC and the hair growth activity test: the small particle size and low viscosity had greater hair growth activity. The usage of solid lipid combination: beeswaxoleum cacao can produce better NLC characteristics and had higher hair growth activity than the formulas that used single lipid.

Effect of Alpha-Lipoic Acid on the Characteristics and Physical Stability of NLC-Green Tea Extract

Background: The addition of alpha-lipoic acid in Nanostructured Lipid Carrier-Green Tea Extract (NLC-GTE) has potential to increase effectiveness of anti-aging preparations. It happened because alpha-lipoic acid can increase stability and antioxidant activity. Objective: Comparing the physical characteristics and stability of NLC-GTE with or without alpha-lipoic acid. Methods: NLC-GTE manufactured using the High Shear Homogenization method. NLC-GTE was divided into two formulas, without the addition of alpha-lipoic acid for F1 and with the addition of alpha-lipoic acid for F2. The characteristics and physical stability were tested, including organoleptic, pH, particle size, and polydispersity index. Stability test was held using the thermal cycling method. Results: Based on characteristic test, it was found that F2 had larger particle size value than F1. The average particle size value of F1 is 313.9 ± 0.76 nm and 423.4 ± 0.75 nm for F2. The F1 and F2 preparations had a polydispersity index value below 0.3, so they were homogeneous. The average pH value of F1 is 5.998 ± 0.01, and F2 is 4.798 ± 0.004. The physical stability test showed a difference before and after the sixth day in particle size and pH, but it was still in the range, so it was safe. However, there was a separation in F1 after day 6. Conclusion: Based on the characteristics and physical stability tests, F1 (without alpha-lipoic acid) and F2 (with alpha-lipoic acid) had differences in particle size and pH. From the physical stability test, it can be concluded that F2 is more stable than F1.

The Effect of Decyl Glucoside on Stability and Irritability of Nanostructured Lipid Carriers-Green Tea Extract as Topical Preparations

Background: Green Tea Extract (GTE) is a natural antioxidant compound that can protect the skin from photocarcinogenesis (DNA damage due to ultraviolet exposure). GTE has low stability, which needs a delivery system such as Nanostructured Lipid Carriers (NLC) with decyl glucoside (DG) as a natural surfactant that at the right concentration can produce a significantly small particle size which can improve the stability of the NLC. Objective: To determine the effect of DG usage on the characteristics, physical stability, and irritability of NLC-GTE preparation. Methods: NLC-GTE preparation used the High Shear Homogenization (HSH) method with three formulas, which contained DG 2%, 2.5%, and 3% consecutively. Afterwards, the characteristic and physical stability tests were conducted using the thermal cycling method for three cycles with two different temperatures (48 hours/cycle, 2 - 8°C and 40°C). The irritability test used Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM) method. Results: Characteristic test of organoleptic showed that all formulas were white, odorless, and had a semi-solid consistency. However, the pH, particle size, and polydispersity index values from all formulas were within the normal range of values. The physical stability test result showed that 3% DG was the most stable formula. This formula was within the non-irritating range of values in HET-CAM. Conclusion: NLC-GTE with an increased concentration of DG as a surfactant can improve the characteristics and physical stability of the preparation. F3 (3% DG) is the best formula compared to other formulas and indicates non-irritating in the HET-CAM test.

Optimization and Fabrication of Curcumin Loaded Solid Lipid Nanoparticles Using Box-Behnken Design for Nasal Delivery

Aims: To prepare curcumin loaded solid lipid nanoparticles for nasal administration using Box-Behnken design. Background: The effectiveness of curcumin in neurological disorders is widely studied by various researchers, but its use is limited due to its poor bioavailability. The brain-targeting efficiency of curcumin can be improved using solid lipid nanoparticles via nasal administration. Objective: In the present work, Curcumin loaded solid lipid nanoparticles (CUR-SLN) were formulated and optimized for nasal administration. Methods: Based on solubility studies, cetostearyl alcohol and poloxamer 407 were selected as lipid and surfactant, respectively. Box-Behnken design (BBD) was used to analyze the effects of drug-to-lipid ratio (X1), surfactant concentration (X2) and homogenization time (X3) on particle size (Y1) and % entrapment efficiency (Y2). The CUR-SLN were formulated by the high shear homogenization method. The optimized formulation was evaluated for DSC, TEM, drug release and ex-vivo studies. Results: Good results were obtained for the particle size and entrapment efficiency analyzed using BBD. The optimized formulation of CUR-SLN obtained using BBD was observed with a particle size of 96.09 nm and % EE of 78.23. In-vitro release of the drug was found to be 82.93± 0.15% after 8 hours. DSC studies revealed that crystalline form of curcumin changed to an amorphous form in SLN. TEM results of optimized CUR-SLN were in correlation with the results obtained using a zeta sizer. No harmful effects were observed on nasal mucosa in the histopathology study. Conclusion: The SLN can be safely utilized for the intranasal administration of curcumin.

Penetration study of p-methoxycinnamic acid (PMCA) in nanostructured lipid carrier, solid lipid nanoparticles, and simple cream into the rat skin

This study compared the ability of Nanostructured Lipid Carrier (NLC), Solid Lipid Nanoparticles (SLN), and Cream systems in delivering para Methoxycinnamic Acid (PMCA) to the dermis layer of the skin. Wistar rats were used as research subjects. NLC and SLN were made by applying the high shear homogenization method. Nile red was used as a penetration indicator based on its fluorescence. The interaction between fluorescence labeled NLC, SLN, or Cream and rat skin was visualized by fluorescence microscopy. Observations were made after 2 and 4.5 h of smearing the test sample. From the observations, it was known that the system/lipid base could penetrate the stratum corneum for delivering drugs. Penetration speed differs among systems as does the number of PMCAs that can be delivered. In this study, it can be concluded that the NLC system is able to deliver PMCA more quickly and in greater quantities to the dermis than SLN and Cream.

Physicochemical Characteristics, Stability, and Irritability of Nanostructured Lipid Carrier System Stabilized with Different Surfactant Ratios

Background: One of the vital variables affecting the stability and the characteristics of the Nanostructured Lipid Carrier (NLC) is the surfactant concentration. Using the two combinations of surfactants can cause higher stability and a better characteristic of NLC. Tween 80 and Span 20 are anionic surfactants whose combination has not been studied for use in NLC systems. Objective: Determine the effect of different surfactant ratios of Tween 80 and Span 20 on the physicochemical characteristics, stability, and irritability of NLC using the High Shear Homogenization (HSH) method. Methods: Four different surfactant ratios were used in the NLC formulation, in which the ratio of Tween 80:Span 20 were 5:5, 6:6, 7:7, and 8:8, respectively. In this NLC system, cetyl palmitate served as solid lipid, medium-chain triglyceride (CrodamolTM) as liquid lipid, Tween 80, and Span 20 as surfactant components. NLC was characterized for organoleptic, viscosity, pH, zeta potential, particle morphology, particle size, and polydispersity index (PDI), then evaluated for stability using the real-time and freeze-thaw method, and irritability effect. Results: The different ratios of Tween 80 and Span 20 had no significant effect on the particle size, PI, and irritation score of the NLC system. On the other hand, it influenced all formulas' pH value, viscosity, zeta potential, and stability. Conclusions: The different ratios of surfactant combination affect the characteristics and stability of the NLC system.

Fenofibrate Characterization of Solid Lipid Nanoparticles Using the High Shear Homogenization Method

Fenofibrate is a drug that can be used to treat hyperlipidemia where the drug is included in the category of Biopharmaceutical classification system II with poor solubility and high permeability. This causes the need to improve the drug delivery system (DDS) made using the solid lipid nanoparticle (SLN) method. SLN fenofibrate can be made using the high shear homogenization method by determining the formula using Factorial 22 Design Expert 12. The formula is made with a concentration of 0.31-1.25% GMS and 1.25-2% Tween-40, then SLN fenofibrate is made by mixing all ingredients until an emulsion is formed and continued with the SLN critical parameter test. From the test results, the critical parameters of SLN fenofibrate for the particle size of 8 formulas 490; 561; 601; 697; 916; 1040; 1818, and 2410 nm. The results obtained for the polydispersity index, respectively, were 0.02; 0.04; 0.08; 0.30; 0.35; 0.48; 0.51, and 0.65. The zeta potential value of the 8 formulas obtained successive values of 2.8; 3.5; 4.2; 4.8; 5.5; 5.8; 8.1, and 8.8 mV. Calculation of the efficiency of the SLN fenofibrate drug obtained successive values of 77.23; 78.53; 79.51; 80.47; 81.17; 87.38; 87.39, and 87.82%. The SLN method can improve drugs that are included in the Biopharmaceutical classification system class II category with the distribution of test results in the particle size range, and the adsorbed drug is more than 70%.

DESIGN OF TEA TREE OIL-LOADED NANOSTRUCTURED LIPID CARRIERS: PREPARATION AND IN VITRO ANTIFUNGAL ACTIVITY

Tea tree oil (TTO) is a promising essential oil that has enormous potential for antifungal development. However, its pharmacological applications have several limitations, including volatility and an extensive range of partition coefficients. To overcome these, TTO can be loaded into a nanostructured lipid carrier (NLC). The combination of solid and liquid lipids and production conditions affect the characteristics of the NLC formed. This study aimed to design TTO-loaded NLCs with appropriate particle sizes to improve the therapeutic efficacy of TTO as an antifungal agent. The novelty of this research is the discovery of a stable and potential TTO loaded NLC formula as a topical antifungal agent. TTO-loaded NLCs were prepared using the high-shear homogenization method with formulas consisting of TTO, solid lipids, liquid lipids, surfactants, and distilled water. Then, they were characterized with particular attention to average particle size, polydispersity, zeta potential, pH, and viscosity. Further tests included physical stability for one month at room temperature (27±2 °C) and in vitro antifungal activity using the well diffusion method. TTO-loaded NLCs combining stearic acid, glyceryl monostearate, and cetyl alcohol (solid lipids) with Miglyol 812 and olive oil (liquid lipids) showed relatively small average particle sizes and low polydispersity index values. Also, the stirring speed did not affect the particle size. It was found that TTO exhibited in vitro antifungal activities as good as ketoconazole cream. This study has successfully combined various solid and liquid lipids to formulate TTO-loaded NLCs with favorable stability for one-month storage and great antifungal potential.

Preparation of solid lipid nanoparticles and nanostructured lipid carriers containing zeaxanthin and evaluation of physicochemical properties

Zeaxanthin is a yellow carotenoid antioxidant concentrated in the macula. This pigment in many foods and beverages is very problematic due to its extreme hydrophobicity and poor chemical stability. Solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) were prepared using a combination of high shear homogenization and ultrasonic methods to load zeaxanthin and reduce its hydrophobicity. In this study, NLCs containing zeaxanthin were produced and optimal formulation was determined and their physicochemical properties were investigated. 20% percent of solid lipid was replaced with Medium-chain triglyceride (MCT) as a liquid lipid to produce NLCs. Results showed that the particle size (PS) of NLCs did not exceed 130 nm, but SLNs did show larger sizes. In addition, particle dispersion index (PDI) showed 0.23 ± 0.01 to 0.34 ± 0.01 and 0.23 ± 0.01 to 0.30 ± 0.01 for SLN and NLC, respectively. Zeta potential (ZP) represented −20.03 ± 0.48 to −12.11 ± 0.80 and −22.23 ± 0.41 to −16.88 ± 0.61 for SLN and NLC, respectively. Encapsulation efficiency and loading were higher for NLCs than SLNs. The morphological study of nanocarriers performed by scanning electron microscope (SEM) showed smooth spherical nanoparticles. Results of Fourier transform infrared spectroscopy (FTIR) analysis, and differential scanning calorimeter (DSC) showed that zeaxanthin was trapped in the nanocarriers without any chemical interaction with the coating material. Glycerol mono-stearate containing zeaxanthin showed phase separation after 60 days at 4 and 25 °C, while this was not observed in nanocarriers produced by glycerol distearate. Together, these nano-based carriers can be applied in many products, especially as nanocarriers for hydrophobic bioactive compounds in nutraceutical beverages.