Lipoid S100 Research Articles

Development and optimization of multivesicular gefitinib liposomal transdermal system employing lipoid S100 for breast cancer: pharmacokinetics, bioavailability, and skin irritation studies in Wistar rats

Abstract Background Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months. Results The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R 2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV, < 100 nm). Importantly, optimized F3-GEF-LIP-TD showed no signs of edema in Wistar rats. The biodistribution of F3-GEF-LIP-TD was similar to pure GEF and was higher in the liver (p < 0.05). The BA of F3-GEF-LIP-TD was observed to be 74.05 ± 0.11% in comparison with oral GEF-LIP (65.25 ± 0.08%) and pure GEF (58.10 ± 0.17%). Conclusion TFH technique offers stable liposomes with high reproducibility. Our findings imply that GEF-LIP-TD provides enhanced BA and tissue distribution and can be considered as a substitution for orals or in combination for treating breast cancer. Lipoid S100 is a potential lipid for developing stable multivesicular nanoliposomes. Graphical abstract

Dissolving microneedle integrated with benidipine loaded ethosomes for transdermal delivery

Benidipine HCl (BEN) is a drug used for the treatment of hypertension. However, this drug suffers from low oral bioavailability. This study introduces a novel approach to address this issue by developing BEN-loaded ethosomes (BEN-E) that integrate into dissolving microneedles for transdermal delivery. The BEN-E was prepared using a rotary evaporation method and optimised using the Box-Behnken design. Following that, the optimised BEN-E formulation was integrated into dissolving microneedles (DMNs). The optimised lipid vesicles selected comprised lipoid S75 (339.66 mg), ethanol (34.51 %), and sonication time (70 s) and showed a vesicle size of 149.4 ± 3.81 nm, an EE% of 88.57 ± 0.38 %, and a transdermal flux of 19.12 ± 0.19 μg/cm²/hr. On the other hand, the resulting BEN-E-DMNs exhibited sharp pyramidal microneedles, sufficient mechanical strength, good insertion capability, and fast dissolution in rat skin. In the ex vivo study, the permeation coefficient of BEN was significantly improved by BEN-E-DMNs compared with optimised BEN-E and BEN-DMNs. The pharmacokinetic studies showed that the BEN-E-DMNs had a Cmax of about 0.698 ± 0.037 μg/mL and an AUC₀₋ₜ of about 15.821 ± 0.868 μg/hr/mL. Moreover, it improved the relative bioavailability of BEN by about 1.58 times compared to the orally marketed BEN tablet and about 2.95 times compared to the BEN-DMNs. In conclusion, the ethosomes combined with dissolving microneedles have shown high potential as carriers for the transdermal delivery of BEN.

Development and evaluation of curcumin-loaded vesicular carriers: impact of formulation variables

Vesicular carriers are a well-established approach to improving the technological and biopharmaceutical characteristics of the loaded cargo. The current manuscript is focused on the development and evaluation in a comparative aspect of two types of vesicles—ethosomes and transfersomes loaded with the phytoconstituent curcumin. The formulation variables affecting their physiochemical and cytotoxic properties are outlined as well. A series of ethosomes and transfersomes based on Lipoid S75 and ethanol, or edge activator, were prepared using the thin film hydration method and subjected to comprehensive evaluation by dynamic light scattering (DLS) analysis, transmission electron microscopy (TEM), entrapment efficiency evaluation, in vitro release, and cytotoxicity studies. Ethosomes based on Lipoid S75 (4% w/w) and ethanol (30% v/v) showed suitable physicochemical characteristics (hydrodynamic diameter of 578.6 nm, monomodal size distribution, high curcumin entrapment efficiency (78.2%)), and superior antiproliferative activity compared to free drug and transfersomal nanocarriers.

Transethosomal Carrier of Curcumin for Improved Topical Delivery: Optimization, In-vitro and Stability Assessment

Objective:: Currently, there is a clear lack of effective topical treatments for psoriasis. In light of this unaddressed requirement, the work intends to develop, enhance, and assess the effectiveness of a curcumin transethosomal gel for managing psoriasis. This work signifies the delivery of a potential solution to fill the gap in topical psoriasis treatment. Material and Methods:: Curcumin-loaded transethosomes were prepared using a mechanical dispersion method. An initial study was conducted to determine the ideal concentrations of Lipoid S100 and Isopropyl Myristate (IPM). To refine the ultimate transethosomal formulation, a full factorial design (32) was employed, incorporating different levels of Lipoid S100 and IPM. Drug release investigations and pharmacokinetics assessments of curcumin concentrations were performed using a specialized dissolution apparatus and an animal model, respectively. Results:: The characterization profile and analytical examinations have affirmed the stability of the formulation throughout the study duration. Our findings indicate that the drug release mechanism conforms to a diffusion pattern akin to Fickian transport. Furthermore, In-vivo investigations revealed that the curcumin concentration in the bloodstream after oral administration was significantly superior to that of the conventional formulation. Conclusion:: Using curcumin-loaded transethosomes extends drug contact time and facilitates controlled drug release, leading to enhanced bioavailability, decreased dosage needs, and heightened patient safety.

RESEARCH ON THE FORMULATION OF NANOPARTICLES CONTAINING MANGIFERIN USING SELF-ASSEMBLY METHOD

Background: The use of natural-origin active compounds in disease treatment is currently a prevailing trend. Mangiferin, a major component found in mangoes, is present in relatively high proportions. However, mangiferin's disadvantages include low solubility and poor permeability. There are numerous methods available to improve solubility and permeability, among which selfassembly is noteworthy. Self-assembly involves the combination of certain molecules or macromolecules to form three-dimensional networks or other structures with new characteristics, phospholipids and chitosan are often used as raw materials for the self-assembly process to create nanoparticles. This method offers advantages such as high efficiency, simple implementation, short execution time, high retention efficiency, and increased permeability through biological membranes. Objectives: To develop a formulation and process for producing nano mangiferin using the selfassembly method with phosphatidylcholine and chitosan. Materials and methods: The solubility of mangiferin in high-proof ethanol was investigated, followed by an assessment of the influence of formulation factors and processes on the characteristics of nano-sized mangiferin particles. Results: The average solubility of mangiferin in 96% ethanol was approximately 0.5529±0.0003 mg/mL. The mole ratio of mangiferin to Lipoid S100 was 1:1, and the mass ratio of Lipoid S100 to chitosan was 20:1. A stirring speed of 1.000 revolutions per minute, reflux temperature of 70°C, reflux time of 2 hours. homogenization speed of 1,000 revolutions per minute, and homogenization time of 15 minutes produced the smallest nanoparticles (103.44±0.46 nm), with a low polydispersity index (0.281±0.009≤ 0.3) and zeta potential (31.95±0.08 mV ≥ +30 mV), encapsulation efficiency of 82.42±0.53%; loading capacity of 32.97±0.95%. Conclusions: A successful formulation of nanosized mangiferin particles was achieved using the self-assembly method, resulting in particles that meet the criteria of small size, uniformity, and durability. Moreover, nearly 100% mangiferin release was achieved after 60 minutes, indicating the promising potential for developing highly bioavailable oral formulations.

Navigating the challenges of lipid nanoparticle formulation: the role of unpegylated lipid surfactants in enhancing drug loading and stability.

Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components (i.e. drug, surfactants and lipids). Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. Our findings demonstrate that the addition of unpegylated lipid surfactant (Lipoid S100) to pegylated lipid surfactant (Brij S20) enhances stability, particularly at higher weight percentages of the core material. This blending approach enables drug loading capacities exceeding 10% in the lipid nanoparticles. Notably, Lipoid S100 exhibited nucleating properties that aided in the formation and stabilisation of the nanoparticles. Furthermore, we examined the incorporation of a model drug into the lipid nanoparticle formulations. Blending the model drug with the core material disrupted the crystallinity of the core, offering additional potential benefits in terms of drug release and stability. This comprehensive investigation provides valuable insights into the interplay between surfactant properties, core material composition, and nanoparticle behaviour. The study enhances our understanding of lipid materials and offers guidance for the design and optimisation of lipid nanoparticle formulations.

Sustained delivery of statistically optimized transfersomal gel of miconazole nitrate for vaginal candidiasis

Miconazole nitrate (MN), an antifungal drug with poor solubility, is used in the treatment of vaginal candidiasis. Conventional vaginal formulations have lower residence time and poor drug penetration resulting in the recurrence of the infection. Hence, transfersomes were formulated that would alleviate fungal infection by improving drug solubility and allowing effective permeation through the vaginal mucus and epithelium. MN-loaded transfersomes (MN-TF) were prepared by the thin film method. The optimization of the MN-TF was done by using 32 full factorial design. The Lipoid S100® and Tween 80® were selected as the phospholipid and edge activator, respectively. The responses, such as particle size, PDI, and entrapment efficiency were studied and found to be 180.70±2.11 nm, 0.293±0.012, and −13.2±1.3 mV, respectively. The optimized MN-TF was incorporated into the thermosensitive gel. The morphological study through TEM confirmed the nano size of the formulation. The FTIR study showed compatibility between the drug and excipients. The microbiological screening was performed against Candida albicans which showed a higher zone of inhibition for MN-TF than the marketed gel. The ex vivo transvaginal permeation study was done for MN-TF gel and compared with the marketed gel Daktarin®. The permeability of the MN-TF was increased by 5.8-folds as compared to the marketed gel. The HET-CAM assay for the MN-TF gel demonstrated no irritation and hence was nontoxic and safe for vaginal administration. Therefore, the MN-TF gel had sustained drug release.

Carvacrol-Loaded Phytosomes for Enhanced Wound Healing: Molecular Docking, Formulation, DoE-Aided Optimization, and in vitro/in vivo Evaluation.

Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing. This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process. Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1. F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation. F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.

Construction and evaluation of a phospholipid-based phase transition in situ gel system for brexpiprazole.

The objective of this study was to develop phospholipid-based injectable phase transition in situ gels (PTIGs) for the sustained release of Brexpiprazole (Brex). Phospholipid (Lipoid S100, S100) and stearic acid (SA) were used as the gel matrix which was dissolved in biocompatible solvent medium-chain triglyceride (MCT), N-methyl pyrrolidone (NMP), and ethanol to obtain PTIGs solution. The Brex PTIG showed a solution condition of low viscosity in vitro and was gelatinized in situ in vivo after subcutaneous injection. Both in vitro release assay and in vivo pharmacokinetics study in SD rats displayed that Brex in PTIGs could achieve a sustained release, compared with brexpiprazole solution (Brex-Sol) or brexpiprazole suspension (Brex-Sus). The Brex-PTIGs had good degradability and biocompatibility in vivo with rare inflammation at the injection site. Among the three Brex-PTIG formulations, Brex-PTIG-3 with the SA in the formulation had the greatest gelation viscosity, the lowest initial release rate, and the most stable release profile with sustained release of up to 60 days. The above results indicated that, as a novel drug delivery system, the Brex-PTIGs offered a new option for the clinical treatment of patients with schizophrenia.

Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment

Onychomycosis accounts for 90% of nail infections worldwide. Topical therapy provides localized effects with minimal adverse systemic actions, yet its effectiveness is limited by minimal drug permeation through the keratinized nail plate. Ciclopirox (CIX) is a FDA-approved broad-spectrum antimycotic agent. However, the complete cure with its nail lacquer (8% w/v) may continue for one year with a high cost. Therefore, poly lactide-co-glycolide (PLGA) nanocapsules (NCs) of CIX were prepared by nanoprecipitation and optimized through a 23 factorial design to be incorporated into hydroxypropyl chitosan (HPCH) based nail lacquer. Nail hydration, in vitro nail absorption, minimum inhibitory concentration (MIC), inhibition zones and ex vivo fungal growth on nail fragments were evaluated. The optimized NCs of CIX based on 100 mg PLGA 2 A and lipoid S75 showed a mean diameter of 174.77 ± 7.90 nm, entrapment efficiency (EE%) of 90.57 ± 0.98%, zeta potential (ZP) of −52.27 ± 0.40 mV and a prolonged drug release. Nail lacquer of the optimized NCs exhibited a higher stability than NCs dispersion. Compared to CIX solution (1% w/v), the respective decrease in MIC for NCs and their lacquer was four- and eight-fold. The lacquer superiority was confirmed by the enhancement in the nail hydration and absorption by 4 and 2.60 times, respectively, relative to CIX solution and the minimal ex vivo fungal growth. Therefore, HPCH nail lacquer of (1% w/v) CIX-PLGA-NCs can be represented as a potential topical delivery system for enhanced in vitro nail absorption and therapeutic efficacy against onychomycosis at a low dose.

TRANSETHOSOMES AS BREAKTHROUGH TOOL FOR CONTROLLED TRANSDERMAL DELIVERY OF DEXKETOPROFEN TROMETAMOL: DESIGN, FABRICATION, STATISTICAL OPTIMIZATION, IN VITRO, AND EX VIVO CHARACTERIZATION

Objective: Transethosomes (TEs) have introduced an emerging avenue of interest in vesicular research for transdermal delivery of drugs and can be a proper delivery system for painkillers like NSAIDS. This study aimed to formulate and characterize the potential of TE to enhance the transdermal transport of Dexketoprofen trometamol (DKT) to achieve controlled pain management compared to DKT solution. Methods: Factorial design (23) was adopted to appraise the influence of independent variables, namely, Lipoid S100 and surfactant concentrations and surfactant type (X3) on the % solubilization efficiency (% SE), vesicle size (VS), and % release efficiency (% RE). Thin film hydration was the preferred approach for preparing TEs where vesicle size, zeta potential, polydispersity index, %SE and %RE were investigated. The optimized formula was nominated and subjected to several studies. For the permeation study, optimum TE was incorporated into carbapol gel base for comparison with DKT solution. Also, an accelerated stability study was assessed for optimized formula. Results: All the prepared DKT-loaded TEs revealed acceptable VS, PDI, and ZP. The highest %SE (86.08±1.05 %) and lowest %RE (44.62±1.36 %) were observed in case of F1. The optimized formula (F1) displayed VS of 133.2±1.62 nm, PDI of 0.342±0.03 and ZP of-21.6±2.45 mV. F1 revealed enhanced skin permeation of a 2.6-fold increase compared with DKT solution. Moreover, F1 was stable upon storage and a non-significant change (P>0.05) was observed. Conclusion: DKT was successfully incorporated into vesicle carrier and can signify an alternative option for providing this therapy, bypassing the poor bioavailability and considerable adverse consequences of using the oral route besides improved patient compliance.

Combretastatin A4-loaded Poly (Lactic-co-glycolic Acid)/Soybean Lecithin Nanoparticles with Enhanced Drug Dissolution Rate and Antiproliferation Activity.

This study aimed to prepare combretastatin A4 (CA4)-loaded nanoparticles (CA4 NPs) using poly(lactic-co-glycolic acid) (PLGA) and soybean lecithin (Lipoid S100) as carriers, and further evaluate the physicochemical properties and cytotoxicities of CA4 NPs against cancer cells. CA4 NPs were prepared using a solvent evaporation technique. The effects of formulations on CA4 NPs were investigated in terms of particle size, zeta potential, encapsulation efficacy, and drug loading. The physicochemical properties of CA4 NPs were characterized using transmission electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectra. The drug release from CA4NPs was performed using a dialysis method. In addition, the cytotoxicity of CA4NPs against human alveolar basal epithelial (A549) cells was also evaluated. CA4 NPs prepared with a low organic/water phase ratio (1:20) and high drug/PLGA mass ratio (1:2.5) exhibited a uniform hydrodynamic particle size of 142 nm, the zeta potential of -1.66 mV, and encapsulation efficacy and drug loading of 92.1% and 28.3%, respectively. CA4 NPs showed a significantly higher release rate than pure CA4 in pH 7.4 phosphate-buffered solution with 0.5% Tween 80. It was found that the drug molecules could change from the crystal state to an amorphous form when loaded into the PLGA/Lipoid S100 matrix, and some molecular interactions could also occur between the drug and PLGA. Importantly, CA4 NPs showed a remarkably higher antiproliferation activity against A549 cancer cells compared to pure CA4. These results suggested the promising potential of PLGA/Lipoid S100 nanoparticles as the drug delivery system of CA4 for effective cancer therapy.

Mitochondria targeted liposomes of metformin for improved anticancer activity: Preparation and evaluation

In recent times, mitochondria have emerged as an effective target for treatment of cancer because of their prominent role in maintaining cellular homeostasis. Metformin hydrochloride (MET), an antidiabetic drug has been reported to be effective against several types of cancers, primarily by acting on mitochondria. So, enabling mitochondria targeted delivery of MET could be an effective strategy for successful chemotherapy. Objective of the study was to develop mitochondria targeted liposomes (Mito-liposomes) of MET for improved therapy of cancer and thereby enable its repurposing for treatment of cancer.In the first step, mitochondria targeting lipid was synthesized by conjugating DPPE (Dipalmitoyl phosphatidyl ethanolamine) with triphenylphosphonium (TPP), a widely reported mitochondria targeting ligand; the synthesized targeting lipid (DPPE-TPP) was confirmed by IR and NMR. Simple liposomes were prepared by thin film hydration technique, wherein Tween 80 was used to maximize MET entrapment; concentrations of Tween 80 and MET were optimized to achieve particle size in the range of 60–100 nm and maximum MET entrapment. To prepare MET Mito-liposomes, the same optimized method was used by replacing 20 μmoles of Lipoid S-100 with DPPE-TPP for mitochondria targeting ability. The MET Mito-liposomes were characterized for various physicochemical properties. Particle size of MET Mito-liposomes were found to be 85.28 ± 0.86 nm with zeta potential of 29.8 ± 1.47 mV. The liposomes and Mito-liposomes provided sustained release of MET for 12 h, compared to 2 h in case of free drug. Evaluation of anticancer activity on HeLa cells was assessed by MTT assay; IC50 values indicated around 15 fold increase in potency of MET Mito-liposomes as compared to free MET. This increased potency may be attributed to mitochondria specific delivery, wherein the Mito-liposomes mediate their activity via mitochondria. In conclusion, targeted delivery of MET to the Mitochondria through Mito-liposomes can provide a novel and versatile approach to achieve improved anticancer activity.

Effects of shell composition in shell-core structured nanoparticles on oral physiological barrier and bioavailability

The present study prepared shell-core nanoparticles comprising poly(lactic-co-glycolic acid)(PLGA) cores encapsulated by shells composed of mixed lipids(Lipoid S100 and DSPE-PEG 2000) or polymer F127 to investigate the effects of shell composition on overcoming physiological barriers of gastrointestinal mucus and intestinal epithelial cells and improving bioavailability.The results are expected to provide references for the research on the improvement of the oral bioavailability of Chinese medicine by nanocar-riers. Silibinin(SLB) was used as a model drug to prepare PLGA nanoparticles coated with the shell of mixed lipids(SLB-LPNs) or F127(SLB-FPNs) via a modified nanoprecipitation method.Transmission electron microscopy showed that both LPNs and FPNs were spherical with a core-shell structure.The average particle sizes of SLB-LPNs and SLB-FPNs were(94.13±2.23) and(95.42±4.91) nm, respectively.The Zeta potential values were(-39.3±2.8) and(-17.0±0.2) mV, respectively.X-ray diffraction analysis revealed the presence of SLB in the two types of nanoparticles in a molecular or amorphous state.The ability of nanoparticles to cross both the mucus and epithelial barriers were evaluated using the cellular internalization kinetics assay.LPNs showed a higher rate of cell internalization than FPNs, indicating that LPNs could penetrate the mucus layer and become internalized by cells more rapidly.As revealed by the in vivo pharmacokinetic assay in rats with SLB suspension as the reference, the relative oral bioavailability of SLB-LPNs and SLB-FPNs was 400.37% and 923.31%, respectively.The effect of SLB-FPNs in improving oral bioavailability was more significant than that of SLB-LPNs.In summary, shell composition can influence the ability of nanoparticles to overcome oral physiological bar-riers, such as the mucus layer and intestinal epithelial cells, and improve oral bioavailability.Shell-core structured nanoparticles are promising nanocarriers for oral drug delivery systems.

Nanoencapsulation of Origanum vulgare essential oil into liposomes with anticancer potential.

Origanum vulgare L. essential oil possesses a wide spectrum of biological activities. Nanoencapsulation of O. vulgare essential oil into liposomes seems to be a promising strategy to maintain and improve these biological properties. This research was carried out to develop a suitable liposomal formulation for the effective encapsulation of O. vulgare essential oil in order to improve the antioxidant and cytotoxic activities. The characterization of liposomal nanocarriers was conducted in terms of size, zeta potential, and encapsulation efficiency. An MTT assay was used to assess the cytotoxic activity of the prepared and characterized O. vulgare essential oil liposomes in MCF-7 cancer cell lines. Antioxidant activity was determined by assessing DPPH scavenging activity. O. vulgare essential oil exerted cytotoxic activity with an IC50 of 50 μg/ml. The essential oil of O. vulgare was effectively encapsulated in liposomes, with no significant change observed among the formulations. The antioxidant activity was significantly enhanced after encapsulating the essential oil in liposomes. Origanum vulgare essential-oil-loaded Phospholipon 90H liposomes demonstrated considerably increased cytotoxic activity against MCF-7 cells, whereas Lipoid S100 liposomes showed no significant differences from the non-encapsulated essential oil. Phospholipon 85G liposomes had the least cytotoxic impact. As a result, liposomes containing O. vulgare essential oil may be promising nanocarriers for the development of anticancer agents.

Optimisation of spray drying process parameters of curcumin nanosuspension

The aim of this study was to optimise spray drying process parameters of curcumin nanosuspension. Method: an I-Optimal experimental model was designed by Design Expert software including 22 experiments. The independent variables were inlet temperature (oC), pump speed (ml/minute) and weight ratio of curcumin-loaded nanoparticles and carrier and nanoparticle; the dependent variables were particle size after redispersing (nm), polydispersity index, dispersion time (second) and spray drying yield. After the optimal parameters had been verified by experiments, some quality requirements of spray-dried powders were evaluated. Then the physical and chemical properties of curcumin in spray-dried powders were studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier-transform infrared spectroscopy (FT-IR). Results: the optimal parameters were established with the inlet temperature of 140oC, the pump speed of 5 ml/minute, the weight ratio of carrier and nanoparticle of 2:1. The obtained results of verification experiments were highly repeatable and were similar to the predicted ones from the software. The comparison of XRD spectra between curcumin crystal and spray-dried powders showed that curcumin in spray-dried powders existed in amorphous form. Furthermore, DSC patterns and FT-IR spectra of curcumin crystal and spray-dried powder demonstrated that there were interactions among curcumin, chitosan and lipoid S100. Conclusion: nano curcumin powders have met the quality requirements of preparation in laboratory-scale. This is a platform for further research later and eventually put into industrial-scale production.

Encapsulation of α-Pinene in Delivery Systems Based on Liposomes and Cyclodextrins.

The essential oil component α-pinene has multiple biological activities. However, its application is limited owing to its volatility, low aqueous solubility, and chemical instability. For the aim of improving its physicochemical properties, α-pinene was encapsulated in conventional liposomes (CLs) and drug-in-cyclodextrin-in-liposomes (DCLs). Hydroxypropyl-β-cyclodextrin/α-pinene (HP-β-CD/α-pinene) inclusion complexes were prepared in aqueous solution, and the optimal solubilization of α-pinene occurred at HP-β-CD:α-pinene molar ratio of 7.5:1. The ethanol-injection method was applied to produce different formulations using saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids in combination with cholesterol. The size, the phospholipid and cholesterol incorporation rates, the encapsulation efficiency (EE), and the loading rate (LR) of α-pinene were determined, and the storage stability of liposomes was assessed. The results showed that α-pinene was efficiently entrapped in CLs and DCLs with high EE values. Moreover, Lipoid S100 CLs displayed the highest LR (22.9 ± 2.2%) of α-pinene compared to the other formulations. Both carrier systems HP-β-CD/α-pinene inclusion complex and Lipoid S100 CLs presented a gradual release of α-pinene. Furthermore, the DPPH radical scavenging activity of α-pinene was maintained upon encapsulation in Lipoid S100 CLs. Finally, it was found that all formulations were stable after three months of storage at 4 °C.

Ocular Application of Oleuropein in Dry Eye Treatment: Formulation Studies and Biological Evaluation.

Background. Oleuropein is already known for its numerous pharmacological properties, but its activity in the ocular field has not yet been investigated. The study aims to verify a possible use of oleuropein (OLE)-based eye drops both in terms of efficacy in dry eye syndrome and stability in aqueous solution. Methods. OLE was co-precipitated with HP-β-cyclodextrin, and the obtained complex was encapsulated into liposomes prepared by hydration of a lipid film composed of Lipoid S100 and cholesterol with different pH buffer solutions. The hydrated vesicles were shrunk by ultrasonication or extrusion. The preparations were characterized from the physicochemical point of view by subjecting them to differential scanning calorimetry, ATR-FTIR, dynamic light scattering analysis, and microscopy. Subsequently, OLE protective activity against hyperosmotic and oxidative stress on rabbit corneal epithelial cells (RCE) was evaluated. Results. The liposomal vesicles obtained after extrusion showed a tendency towards greater encapsulation efficiency (up to 80.77%) compared to that obtained by sonication, and the liposomes hydrated in pH 5.5 solution tended to incapsulate more than the neutral ones. Ultrasonication produced two-dimensional populations of liposomes, the largest of which reached 2149 nm. On the contrary, the extruded liposomes showed homogeneous diameters of about 250 nm. Complexation with cyclodextrin and subsequent encapsulation in liposomes greatly increased the OLE stability in aqueous solution, especially at 4 °C and for the extruded formulations. OLE aqueous solution (OLE7.4-sol, reference) and neutral extruded liposomes (F7.4-e) were well tolerated on RCE cells. Moreover, OLE was able to control the effects of hyperosmolarity on ocular surface cells and to prevent oxidative stress-induced loss of cell viability.

Development and evaluation of a novel nanofibersolosome for enhancing the stability, in vitro bioaccessibility, and colonic delivery of cyanidin-3-O-glucoside

The development of colon-specific carrier systems using polysaccharides for oral delivery of nutraceuticals is of great importance for the treatment and/or prevention of inflammatory bowel diseases. In this study, self-assembly with the assistance of vortexing and pulsed-ultrasonication was employed to develop a Fibersol®-2 (a digestion-resistant polysaccharide) and lipoid S75 based novel nanocarrier (denoted as nanofibersolosome) for the colonic delivery of cyanidin-3-O-glucoside (C3G). A series of nanofibersolosome formulations (CFS-0.5–4, 0.5–4 represent the ratios of Fibersol®-2:lipoid S75) were developed and their performance was compared with Fibersol®-2-free reference lipid formulation (CFS-0). The nanofibersolosomes (<150 nm) were spherical and unilamellar with high negative surface charge (−38 to −51 mV) and good encapsulation efficiency (EE > 90%). They performed much better than CFS-0 in retaining their physical properties during freeze drying, preventing particle aggregation, and retaining C3G during storage (4 and 25 ℃) and thermal treatments (40, 60, and 80 ℃). They also exhibited significantly higher stability during simulated gastrointestinal digestion than CFS-0. These desirable features of the nanofibersolosomes (especially CFS-0.5 and CFS-1) led to the efficient delivery of higher concentrations of C3G to the colon than CFS-0. Moreover, gastrointestinal-digested and colonic-fermented nanofibersolosome samples exhibited significantly higher DPPH radical scavenging activity and stronger promoting effect on short-chain fatty acid generation than CFS-0. These in vitro findings indicate that the novel nanofibersolosome possesses great potential for the colonic delivery of C3G and likely other hydrophilic labile phytochemicals that merits further evaluation in in vivo models.

Stability evaluation of interdigitated liposomes prepared with a combination of 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine and 1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine

AbstractBACKGROUNDIn order to obtain small and homogenous liposomes encapsulating gallic acid (GA) with interdigitated leaflets, a combination of phosphatidylcholine (PC) of medium length sn‐1 and sn‐2 acyl chains with PC of longer acyl chains at both sn1 and sn2 positions were employed. Four formulations respectively consisting of 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC); DSPC/1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine (DSPC/DLPC) (1:1, mol mol−1); DSPC/DLPC (3:1, mol mol−1) and Lipoid S75, were prepared. For each formulation, the stability of liposomes during storage was investigated.RESULTSThe initial size of liposomes ranged from 36.61 ± 0.61 to 125.43 ± 2.15 nm and their polydispersity index (PDI) from 0.14 ± 0.01 to 0.28 ± 0.01. The formulations combining DSPC and DLPC resulted in very stable liposomes physically, during up to 84 days of storage with no significant change in both size and PDI except a slight increase in the size at the 42nd day. The molecular state of the bilayers and their thermal behavior as given by FTIR and Differential Scanning Calorimetry (DSC) results supported the hypothesis of an interdigitated state of the liposomes formed by DSPC/DLPC combination at a molar ratio of 3:1 .CONCLUSIONInterdigitated liposomes composed of two symmetric phospholipids (DSPC and DLPC) were obtained for the first time and exhibited a good stability during storage in solution. © 2021 Society of Chemical Industry (SCI).