Novel composite fatty acid vesicles-in-Pluronic lecithin organogels for enhanced magnolol delivery in skin cancer treatment.

A novel composite carrier composed of Pluronic lecithin organogels and fatty acid vesicles was used to enhance the stability and facilitate the topical delivery of a natural bioactive drug, magnolol (Mag), for treatment of skin cancer. Jojoba oil was incorporated in the organogel (OG) base to provide a synergistic effect in treatment of skin cancer. The organoleptic properties, rheological behavior, morphology, and drug content of the OG formulations were investigated with emphasis on the impact of vesicle loading on the OG characteristics. The effect of OG on Mag release and ex-vivo permeation studies were evaluated and compared to free Mag in OG. The biological anti-tumor activity of the OG formulae was assessed using a skin cancer model in mice. All OG formulations exhibited uniform drug distribution with drug content ranging from 92.22 ± 0.91 to 100.45 ± 0.77 %. Rheological studies confirmed the OG shear-thinning flow behavior. Ex-vivo permeation studies demonstrated that the permeation of Mag from all OG formulations surpassed that obtained with free Mag in the OG. The anti-tumor activity studies revealed the superior efficacy of 10-hydroxy-decanoic acid (HDA)-based vesicles incorporated in OG formulations in mitigating 7,12- dimethylbenz(a)anthracene (DMBA)-induced skin cancer, thereby offering a promising platform for the local delivery of Mag.

Ufosomes as Topical/Transdermal Drug Delivery System: Structural Components, Preparation Techniques and Therapeutic Application.

Fatty acid vesicles, or ufasomes, are spherical structures that encapsulate and deliver bioactive molecules to the skin or other tissues. They are formed from both saturated and unsaturated fatty acids and offer advantages over liposomes, including greater stability and a wider range of pH compatibility. They are composed of two layers of fatty acid molecules with their hydrocarbon tails facing inwards and their carboxylic groups facing outwards. The space between the two layers is filled with surfactants. There are various methods for characterizing and evaluating the properties of vesicles and drug-loaded vesicles, such as differential scanning calorimetry (DSC), Electron microscopy, UV-visible spectrophotometry, Dialysis, Franz diffusion cell, and stability testing. Each method provides specific information about the vesicles, such as their size, zeta potential, morphology, drug content, entrapment efficiency, drug release, permeability, and stability. Ufasomes have potential applications in topical/transdermal drug delivery as food additives, cosmetics, vaccines, gene therapy vectors, and diagnostic tools. Their ability to encapsulate and deliver bioactive molecules makes them valuable in various fields, including drug delivery and biomedical research. In summary, fatty acid vesicles represent a versatile drug delivery system with potential applications in various fields.

10-Hydroxy Decanoic Acid-Based Vesicles as a Novel Topical Delivery System: Would It Be a Better Platform Than Conventional Oleic Acid Ufasomes for Skin Cancer Treatment?

10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of novel fatty acid vesicles for comparison with oleic acid (OA) ufasomes. The vesicles were loaded with magnolol (Mag), a potential natural drug for skin cancer. Different formulations were prepared using the thin film hydration method and were statistically evaluated according to a Box-Behnken design in terms of particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The ex vivo skin permeation and deposition were assessed for Mag skin delivery. In vivo, an assessment of the optimized formulae using 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in mice was also conducted. The PS and ZP of the optimized OA vesicles were 358.9 ± 3.2 nm and -82.50 ± 7.13 mV compared to 191.9 ± 6.28 nm and -59.60 ± 3.07 mV for HDA vesicles, respectively. The EE was high (>78%) for both types of vesicles. Ex vivo permeation studies revealed enhanced Mag permeation from all optimized formulations compared to a drug suspension. Skin deposition demonstrated that HDA-based vesicles provided the highest drug retention. In vivo, studies confirmed the superiority of HDA-based formulations in attenuating DMBA-induced skin cancer during treatment and prophylactic studies.

Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation.

Peripheral nerve injuries significantly impact patients' quality of life and poor functional recovery. Chitosan-ufasomes (CTS-UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS-UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO-UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (24). The influence of formulation factors on UFAs' physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert® software. Based on the optimal UFA formulation, PRO-CTS-UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO-CTS-UFA and PRO-UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO-UFAs and PRO-CTS-UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of -62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO-CTS-UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS-UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage.

Micron and nano hybrid ufasomes from conjugated linoleic acid, their vesiculation and encapsulation of ginsenoside Rg3.

BACKGROUND: Unsaturated fatty acids used to form unstable micro-vesicles, while conjugate linoleic acid (CLA)-sodium dodecyl sulfate (SDS) can self-assembly to stable nano-conjugate linoleic acid vesicles (nano-CLAVs). Generally, micro-capsule could geometrically provide higher loading capacity but also generate concerns in construction convenience, sustained release, bioaccessibility and stability. Hence there is a contradiction between loading capacity and encapsulation efficiency. Therefore, the study of the factors that decide the capsule size falling in nano or micron size with same capsule material would be a benefit to food or drug delivery science. RESULTS: The micron- and nano-CLAVs were constructed for encapsulation and sustained release of ginsenoside Rg3. The formation mechanism of nano or micron capsule,s the effect of vesicle sizes on encapsulation efficiency, drug loading efficiency and stability of the encapsulated Rg3 were investigated. It was found that with the addition of salt (PBS), the size of CLAVs jumped from nano to micron. Furthermore, the salt concentration is the key factor that decides the vesicle size of nano or micron. The pH at fabrication triggers the vesiculation and dramatically affects the vesicle size over the nano and micron scales. CONCLUSION: Compared to the nano-CLAVs, micron vesicles enhanced the loading capacity to 137.6% and the encapsulation efficiency to 138.4%, respectively. Meanwhile, the micron-CLAVs performed similar sustained release of Rg3 as the nano-CLAVs did, and was stable for 120 days at room temperature or sustained 98.9% of capsules after centrifuge at 6090 × g for 20 min. © 2022 Society of Chemical Industry.

Itraconazole-Loaded Ufasomes: Evaluation, Characterization, and Anti-Fungal Activity against Candida albicans.

Numerous obstacles challenge the treatment of fungal infections, including the uprising resistance and the low penetration of available drugs. One of the main active agents against fungal infections is itraconazole (ITZ), with activity against a broad spectrum of fungi while having few side effects. The aim of this study was to design ufasomes, oleic acid-based colloidal carriers, that could encapsulate ITZ to improve its penetration power. Employing a 2231 factorial design, the effect of three independent factors (oleic acid amount, cholesterol concentration, and ITZ amount) was investigated and evaluated for the percentage encapsulation efficiency (%EE), particle size (PS), and zeta potential (ZP). Optimization was performed using Design® expert software and the optimized ITZ-loaded ufasomes obtained had %EE of 99.4 ± 0.7%, PS of 190 ± 1 nm, and ZP of -81.6 ± 0.4 mV, with spherical unilamellar morphology and no aggregation. An in vitro microbiological study was conducted to identify the minimum inhibitory concentration of the selected formula against Candida albicans, which was found to be 0.0625 µg/mL. Moreover, the optimized formula reduced the expression of toll-like receptors-4 and pro-inflammatory cytokine IL-1ß secretion in the C. albicans-infected fibroblasts, indicating that the proposed ITZ-loaded ufasomes are a promising drug delivery system for ITZ.

Lipid-Based Nanovesicular Drug Delivery Systems.

In designing a new drug, considering the preferred route of administration, various requirements must be fulfilled. Active molecules pharmacokinetics should be reliable with a valuable drug profile as well as well-tolerated. Over the past 20 years, nanotechnologies have provided alternative and complementary solutions to those of an exclusively pharmaceutical chemical nature since scientists and clinicians invested in the optimization of materials and methods capable of regulating effective drug delivery at the nanometer scale. Among the many drug delivery carriers, lipid nano vesicular ones successfully support clinical candidates approaching such problems as insolubility, biodegradation, and difficulty in overcoming the skin and biological barriers such as the blood-brain one. In this review, the authors discussed the structure, the biochemical composition, and the drug delivery applications of lipid nanovesicular carriers, namely, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, catanionic vesicles, and extracellular vesicles.

Oleuropein-Laded Ufasomes Improve the Nutraceutical Efficacy.

Ufasomes are unsaturated fatty acid liposomes made up of oleic and linoleic acids, natural components required in various biological processes. This kind of nanocarrier is characterized by a simple and dynamic structure and is able to improve the bioavailability of unsaturated fatty acids. The aim of this investigation was to evaluate ufasomes as natural compound delivery systems to deliver oleuropein and improve its antioxidant activity. Oleuropein is a phenolic compound mainly present in olives and olive oil, with several biological properties, such as the antioxidant activity. However, to improve their biological activity, antioxidant compounds should be able to cross cell membranes and uniformly incorporate in cells. Because of the great similarity between their constituents and cell membranes, ufasomes could be advantageous carriers for oleuropein delivery. The physico-chemical characteristics of ufasomes were investigated. A regular shape was shown by transmission electron microscopy studies, while the mean sizes were dependent on the ufasomes composition. In vitro studies highlighted that empty ufasomes did not lead to cell mortality at the tested concentrations and a good carrier internalization in CaCo-2 cells, further studies in vitro studies demonstrated that oleuropein-loaded ufasomes were able to enhance the antioxidant activity of the free active substance making this carrier a suitable one for nutraceutical application.

Oleic Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery.

Current topical minoxidil (MXD) formulations involve an unpleasant organic solvent which causes patient incompliance in addition to side effects in some cases. Therefore, the objective of this work was to develop an MXD formulation providing enhanced follicular delivery and reduced side effects. Oleic acid, being a safer material, was utilized to prepare the nanovesicles, which were characterized for size, entrapment efficiency, polydispersity index (PDI), zeta potential, and morphology. The nanovesicles were incorporated into the emugel Sepineo® P 600 (2% w/v) to provide better longer contact time with the scalp and improve physical stability. The formulation was evaluated for in vitro drug release, ex vivo drug permeation, and drug deposition studies. Follicular deposition of the vesicles was also evaluated using a differential tape stripping technique and elucidated using confocal microscopy. The optimum oleic acid vesicles measured particle size was 317 ± 4 nm, with high entrapment efficiency (69.08 ± 3.07%), narrow PDI (0.203 ± 0.01), and a negative zeta potential of -13.97 ± 0.451. The in vitro drug release showed the sustained release of MXD from vesicular gel. The skin permeation and deposition studies revealed superiority of the prepared MXD vesicular gel (0.2%) in terms of MXD deposition in the stratum corneum (SC) and remaining skin over MXD lotion (2%), with enhancement ratios of 3.0 and 4.0, respectively. The follicular deposition of MXD was 10-fold higher for vesicular gel than the control. Confocal microscopy also confirmed the higher absorption of rhodamine via vesicular gel into hair follicles as compared to the control. Overall, the current findings demonstrate the potential of oleic acid vesicles for effective targeted skin and follicular delivery of MXD.

Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging.

To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3(1)4(1) full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps' nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery.

Molecular dynamics simulation of oleic acid/oleate bilayers: an atomistic model for a ufasome membrane.

When oleic acid and oleate coexist in comparable amounts they form unilamellar vesicles called ufasomes in aqueous phase. Intrinsic pH sensitivity of ufasomes makes it an attractive vehicle for drug delivery. Physical properties of ufasomes have been studied by using spectroscopic techniques but an atomistic model for a ufasome has not been proposed. In this study molecular dynamics simulation was performed on oleic acid/oleate bilayers with the oleate concentration varying from 40 to 70 mol%. All the bilayers reached an equilibrium and stayed stable during a 40 ns simulation. Area per lipid increased with mol% of oleate probably due to charge repulsion between anionic oleate molecules. Oleate was pulled out toward the aqueous phase so that the carboxyl groups of oleic acid and oleate were separated by 0.392 nm in the bilayer of oleic acid/oleate 1:1. Water concentration at the depth of carboxyl group of oleate was five times as high as that of oleic acid. Number of hydrogen bonds between oleic acid and oleate was small in contrast to a proposal that it is an important factor for the bilayer stability. However there was an extensive array of hydrogen bonds between the lipids and water molecules. Acyl chain order was within a normal range for a lipid bilayer but lateral diffusion was an order of magnitude faster in oleic acid/oleate bilayer than in dioleoylphosphatidylcholine bilayer. Cholesterol increased the bilayer thickness and order parameter and decreased the rate of lateral diffusion.