Dissolution and antioxidant potential of apigenin self nanoemulsifying drug delivery system (SNEDDS) for oral delivery.

Self-nanoemulsifying drug delivery systems (SNEDDS) have been used to improve the oral bioavailability of various drugs. In the current study, apigenin was developed as SNEDDS to solve its dissolution problem and enhance oral bioavailability and antioxidant potential. SNEDDS were prepared by mixing Gelucire 44/14, Tween 80, and PEG 400 under controlled conditions. The droplet of diluted SNEDDS demonstrated a spherical shape with a size of less than 100 nm and a neutral charge. The very fast self-emulsification was obtained within 32 s, and the transmittance values exceeded 99%. The highest drug loading was 90.10 ± 0.24% of the initial load with the highest %encapsulation efficiency of 84.20 ± 0.03%. FT-IR and DSC spectra showed no interaction between components. The dissolution in buffer pH 1.2, 4.5, and 6.8 showed significantly higher dissolved apigenin than the apigenin coarse powder. The dissolution profiles were fitted to the Korsmeyer-Peppas kinetics. The cellular antioxidant activities in Caco-2 cells were approximately 52.25-54.64% compared to no treatment and were higher than the apigenin coarse powder (12.70%). Our work highlights the potential of SNEDDS to enhance the dissolution and permeability of apigenin and promote antioxidant efficacy, which has a strong chance of being developed as a bioactive compound for nutraceuticals.

Cannabidiol-Loaded Nanostructured Lipid Carriers (NLCs) for Dermal Delivery: Enhancement of Photostability, Cell Viability, and Anti-Inflammatory Activity.

The aim of this study was to encapsulate cannabidiol (CBD) extract in nanostructured lipid carriers (NLCs) to improve the chemical stability and anti-inflammatory activity of CBD for dermal delivery. CBD-loaded NLCs (CBD-NLCs) were prepared using cetyl palmitate (CP) as a solid lipid and stabilized with Tego® Care 450 (TG450) or poloxamer 188 (P188) by high-pressure homogenization (HPH). The CBD extract was loaded at 1% w/w. Three different oils were employed to produce CBD-NLCs, including Transcutol® P, medium-chain triglycerides (MCT), and oleic acid (OA). CBD-NLCs were successfully prepared with an entrapment efficiency (E.E.) of 100%. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10. The type of surfactant and oil used affected the particle sizes, zeta potential, and crystallinity of the CBD-NLCs. CBD-NLCs stabilized with TG450 showed higher crystallinity after production and storage at 30 °C for 30 days as compared to those with P188. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m2) compared to that of the CBD extract in ethanolic solution. The CBD-NLCs prepared from MCT and OA showed slower CBD release compared with that from Transcutol® P, and the kinetic data for release of CBD from CBD-NLCs followed Higuchi's release model with a high coefficient of determination (>0.95). The extent of CBD permeation through Strat-M® depended on the oil type. The cytotoxicity of the CBD extract on HaCaT and HDF cells was reduced by encapsulation in the NLCs. The anti-inflammatory activity of the CBD extract in RAW264.7 cell macrophages was enhanced by encapsulation in CBD-NLCs prepared from MCT and OA.

Influence of Vegetable Oils on In Vitro Performance of Lutein-Loaded Lipid Carriers for Skin Delivery: Nanostructured Lipid Carriers vs. Nanoemulsions.

Nanostructured lipid carriers (NLC) were prepared from solid lipid (glyceryl monostearate, GMS) and vegetable oils, including palm oil (PO), rice bran oil (RBO) or virgin coconut oil (VCO), at different ratios (95:5, 90:10 and 80:20), while nanoemulsions (NE) were prepared with sole vegetable oils. After production, the particle size of the lutein-free NLC and NE was found to be between 100 and 150 nm and increased after loading with lutein. An increase in oil loading in NLC reduced the particle size and resulted in a less ordered lipid matrix and an increase in % entrapment efficiency. From the stability study, it was observed that the types of oils and oil content in the lipid matrix had an impact on the chemical stability of lutein. Regarding the release study, lutein-loaded NE showed higher release than lutein-loaded NLC. Both NLC and NE prepared from VCO exhibited higher release than those prepared from PO and RBO, respectively (p < 0.05). In contrast, among the formulations of NLC and NE, both lutein-loaded NLC and NE prepared from RBO showed the highest permeation through the human epidermis due to the skin enhancement effect of RBO. Based on all the results, the lipid nanocarriers composed of RBO could effectively enhance the chemical stability of lutein and promote drug penetration into the skin.

Pumpkin Seed Oil-Loaded Niosomes for Topical Application: 5α-Reductase Inhibitory, Anti-Inflammatory, and In Vivo Anti-Hair Loss Effects.

Pumpkin seed oil (PSO)-loaded niosomes were prepared from Tween 20 and cholesterol by ethanol injection. Confocal microscopy showed better skin permeation and hair follicle accumulation of the niosomes compared to the PSO solution. The PSO-loaded niosomes inhibited 5α-reductase activity in DU-145 cells and hindered IL-6 activity in RAW 264.7 cells. These effects indicated the great potential of PSO-loaded niosomes to reduce hair loss. The hair scalp serum with PSO-loaded niosomes did not show irritation to reconstructed human skin. This formulation presented a significant decrease in the percentage of fallen hairs by 44.42% in the in vivo 60-second hair count experiment and a significant increase in the anagen to telogen (A/T) ratio (1.4-fold) in the TrichoScan® evaluation after 8 weeks of treatment compared to the initial conditions, indicating the promising efficacy of PSO-loaded niosomes as a natural alternative for anti-hair loss therapy.

Phyllanthus emblica Extract-loaded Transfersomes for Hair Follicle Targeting: Phytoconstituents, Characterization, and Hair Growth Promotion.

Phyllanthus emblica Linn. (PE) has been used to promote hair growth for decades. In this study, dried PE fruit powder was extracted, tested for biological activities, and loaded into transfersomes for hair follicle targeting. Before lyophilization, PE fruit powder was extracted using 2 solvent systems, water and 30% ethanol. The PE 30% ethanolic extract had higher antioxidant activity and total phenolic content than the PE aqueous extract. However, the cytotoxicity of the PE 30% ethanolic extract was higher than that of PE aqueous extract. As a result, the PE aqueous extract was analyzed using ultra-performance liquid chromatography and found that the major component of the PE aqueous extract was gallic acid. Afterward, the PE aqueous extract was tested for its potential to activate the expression of genes involved in hair growth promotion in human keratinocytes. At a non-toxic concentration (10 µg/mL), this extract promoted various growth factors comparable to 1% minoxidil. PE-loaded transfersomes were prepared to deliver the PE aqueous extract to the hair follicle. The particle size and polydispersity index of PE-loaded transfersomes were 228 nm and 0.25, respectively. After 3 months of storage, the particle size at 4°C and 30°C was 218 nm and 241 nm, respectively, which was comparable to its initial size. However, at 40°C, the particle size dramatically increased (315 nm). The fluorescent agent, rhodamine B, was used to evaluate the potential of transfersomes to target hair follicles. Rhodamine B transfersomes had better penetration and accumulation in hair follicles than rhodamine B solution. To conclude, the PE aqueous extract, mainly composed of gallic acid, can activate hair growth gene expression. The extract can be loaded into hair follicles targeting transfersomes. Thus, PE-loaded transfersomes are a promising delivery system for hair follicle targeting to promote hair growth.

Effect of Lipid and Oil Compositions on Physicochemical Properties and Photoprotection of Octyl Methoxycinnamate-loaded Nanostructured Lipid Carriers (NLC).

This study aimed to evaluate the effect of solid lipid and oil structures on the physicochemical properties, kinetic release, photostability, and photoprotection of nanostructured lipid carriers (NLC) containing octyl methoxycinnamate (OMC). OMC was used as a model compound since it is an effective sunscreen agent and is widely used in sunscreen products; however, it is unstable after ultraviolet radiation (UVR) exposure. OMC-loaded NLC were prepared from different solid lipids (cetyl palmitate (CP) or tristearin) and oils (caprylic/capric triglyceride, isopropyl myristate or isononyl isononanoate) at a 4:1 ratio. After production, the particle size (z-ave) and polydispersity index (PDI) of OMC-loaded NLC ranged from 190 to 260 nm and were lower than 0.25, respectively, and the zeta potential (ZP) values were higher than |50 mV|. The Fourier transform infrared (FTIR) spectroscopy results indicated no interaction among the components. Data obtained from differential scanning calorimetry (DSC) and X-ray diffraction showed that the incorporation of oil into solid lipids disturbed the crystallinity of the lipid matrix, depending on the structure of the oil molecule. OMC loaded in tristearin-based NLC (OMC-tristearin-NLC) showed higher release of OMC than OMC loaded in CP-based NLC (OMC-CP-NLC). For photostability properties, OMC-CP-NLC prepared from isononyl isononanoate showed the highest stability owing to the less-ordered structure, providing space for accommodation of OMC, whereas the percentage of OMC remaining in tristearin-based NLC was comparable. Therefore, the degree of protection was dependent on the type of solid lipid and oil. As a result, branched-chain fatty acids provided a higher degree of disturbance than linear-chain fatty acid.

Niosomal delivery of pumpkin seed oil: development, characterisation, and physical stability.

Pumpkin seed oil (PSO) provides many health benefits including antioxidant, cardiovascular health boost, treatment of benign prostatic hyperplasia (BPH), and reduction of hair loss. The main objective of this study was to design a suitable formulation of niosomes encapsulated PSO for topical delivery. Formulation of PSO-loaded niosomes was optimised by altering the types of surfactant and the amount of PSO:surfactant:cholesterol. The developed PSO-loaded niosomes were spherical shape with the size range of 138-366 nm. The niosomes formulated with Tween 20 provided the smallest particle size. An increase in the ratio of PSO:surfactant:cholesterol from 2:2:1 to 2:4:1 led to reduction of the particle size of the niosomes. The PSO-loaded niosomes formulation F1 (PSO:Tween 20:cholesterol = 2:2:1) provided the highest percent entrapment efficacy at 75.99 ± 14.65%. The in vitro release study suggested that the release mechanism was followed Korsmeyer-Peppas. The physical stability study indicated good stability over 3 months of storage at 30 °C.

Dissolution enhancement and in vitro performance of clarithromycin nanocrystals produced by precipitation-lyophilization-homogenization method.

The gastroduodenal diseases caused by Helicobacter pylori were commonly treated with antibiotic clarithromycin as a standard regimen. According to the poorly water-soluble of clarithromycin, the nanocrystal formulation was prepared. The aim of this study was to investigate an enhancement effect of clarithromycin nanocrystals produced by precipitation-lyophilization-homogenization (PLH) method on the saturation solubility, dissolution velocity, antibiotic activity, permeability through the gastric mucus and cellular permeability. Poloxamer 407 and sodium lauryl sulfate (SLS) were chosen as combined stabilizers in the nanocrystal system. The obtained clarithromycin nanocrystals were identified as cubic particles by SEM with a bulk population of approximately 400nm existed in crystalline and/or partial amorphous form as investigated by DSC and XRPD. The saturation solubility of the clarithromycin nanocrystals was increased by 1.5- and 6-folds higher than clarithromycin powder in buffer pH 5.0 and 6.8, respectively. The dissolution profiles of clarithromycin nanocrystals at pH 5.0 and 6.8 were significantly different from clarithromycin powder and the marketed product (f1 value >15 and f2 value <50). All dissolution parameters (relative dissolution rate, percent dissolution efficiency and mean dissolution time) showed that clarithromycin nanocrystals had higher dissolution rate when compared with the clarithromycin powder, the lyophilized coarse suspension and the marketed product. The bioassay study by diffusion agar method showed a maintained antibiotic activity of clarithromycin nanocrystals solubilized in buffer solution which was greater potency than the lyophilized coarse suspension and the clarithromycin powder. Additionally, the nanocrystals possessed higher permeability through gastric mucus and cellular monolayer of Caco-2 and NCI-N87 cells as compared to the lyophilized coarse suspension and the clarithromycin powder. The results indicated that, the developed clarithromycin nanocrystals were a potential delivery system that exerts more effectiveness in H. pylori eradication.

Precipitation-lyophilization-homogenization (PLH) for preparation of clarithromycin nanocrystals: influencing factors on physicochemical properties and stability.

Nanocrystals is one of effective technologies used to improve solubility and dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS class II having low bioavailability due to very low dissolution behavior. The main purpose of this study was to investigate an efficiency of clarithromycin nanocrystals preparation by precipitation-lyophilization-homogenization (PLH) combination method in comparison with high pressure homogenization (HPH) method. The factors influencing particle size reduction and physical stability were assessed. The results showed that the PLH technique provided an effective and rapid reduction of particle size of nanocrystals to 460 ± 10 nm with homogeneity size distribution after only the fifth cycle of homogenization, whereas the same size was attained after 30 cycles by the HPH method. The smallest nanocrystals were achieved by using the combination of poloxamer 407 (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the particle aggregation over 3-month storage at 4 °C. The results from SEM showed that the clarithromycin nanocrystals were in cubic-shaped similar to its initial particle morphology. The DSC thermogram and X-ray diffraction pattern of nanocrystals were not different from the original drug except for intensity of peaks which indicated the presenting of nanocrystals in the crystalline state and/or partial amorphous form. In addition, the dissolution of the clarithromycin nanocrystals was dramatically increased as compared to the coarse clarithromycin.