Lactoferrin (Lf), a multifunctional glycoprotein known for its roles in immune modulation, iron metabolism, and antimicrobial activity, has limited therapeutic efficacy due to poor bioavailability. Liposomal encapsulation of lactoferrin (LLf) offers a potential solution by improving its stability, absorption, and sustained release, making it a promising candidate for various clinical applications. This study aims to compare the effectiveness of LLf and plain Lf in cellular uptake, proliferation, and wound healing using HEK-293T and Caco-2 cell lines.

In this study, liposomes consisting of soybean phosphatidyl choline (SoyPC) and different molar concentrations (10 mol% and 20 mol%) of dioleoyl trimethylammoniumpropane (DOTAP) were prepared by the thin film hydration method and coated with sodium hyaluronate (NaHA) of different MWs (8-15 kDa, 30-50 kDa and 90-130 kDa) and concentrations (0.01-0.2% w/w) using phosphate buffer (PB) or glycerol phosphate buffer (G-PB) as the hydration medium. These NaHA coated liposomes could have a potential in the treatment of dry mouth since glycerol and NaHA are known for their lubricating and hydrating properties. The liposomes composed of SoyPC-DOTAP 20 mol%, and coated with NaHA MW 90-130 kDa, 0.05% w/w were found to be most stable during storage. The liposomes with 20 mol% DOTAP coated with NaHA MW 30-50 kDa, 0.05% w/w showed promising results as these stayed stable for at least two weeks. However, the liposomes coated with NaHA MW 8-15 kDa were generally unstable irrespective of the combinations of the investigated parameters. When the stable liposomes were introduced into artificial saliva (AS), aggregation rapidly occurred. Sodium alginate (NaAlg) coated liposomes that were prepared for comparison were found to be stable in AS. The study has demonstrated the influence of the amount of charged lipid which must be high, the polymer MW which must lay in the area 30 kDa-130 kDa and coating concentration which should be intermediate 0.05% w/w in preparing stable NaHA coated liposomes. Further studies need to be conducted to understand the instability exhibited by the NaHA coated liposomes in AS.

Gangliosides, glycosphingolipids with one or more N-acetyl-neuraminic acid groups, play essential roles in various cellular and biological processes, among them are cell signaling, neuronal development, cell-cell recognition and the modulation of immune response. Based on their multiple biological roles, the pharmacological utilization of gangliosides for the therapy of several clinical conditions is currently widely being explored but hampered by its limited water solubility. To increase the bioavailability of poorly water-soluble therapeutic agents, pharmaceutical nanocarriers such as liposomes have been developed over the last fifty years. Ganglioside GM1 incorporated into liposomes was proposed during the 1980s for rendering them long-circulating following their intravenous administration, but GM1 was soon replaced by polyethylene glycol which gave rise to the concept of Stealth Liposomes. More recently, the ability of exogenous GM1 to ameliorate oxidative stress was revealed, leading us to investigate the cytoprotective effect of liposomal GM1 under a variety of pathological conditions. Here we review all data showing the antioxidant effect of exogeneous GM1 and based on literature findings and our own, we propose a mechanism by which liposomal exogenous GM1 is able to trigger the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which is a critical cellular defense mechanism protecting against oxidative stress and other types of cellular damage.

This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A (sPLA) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A (sPLA). experiment, the sPLA levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5-4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.

Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and and drug release. An study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. and drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.

Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (-33.33 ± 1.5 and -48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant ( < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.

Liver disorders present a significant global health challenge, necessitating the exploration of innovative treatment modalities. Liposomal nanocarriers have emerged as promising candidates for targeted drug delivery to the liver. This review offers a comprehensive examination of the mechanisms and applications of liposomal nanocarriers in addressing various liver disorders. Firstly discussing the liver disorders and the conventional treatment approaches, the review delves into the liposomal structure and composition. Moreover, it tackles the different mechanisms of liposomal targeting including both passive and active strategies. After that, the review moves on to explore the therapeutic potentials of liposomal nanocarriers in treating liver cirrhosis, fibrosis, viral hepatitis, and hepatocellular carcinoma. Through discussing recent advancements and envisioning future perspectives, this review highlights the role of liposomal nanocarriers in enhancing the effectiveness and the safety of liver disorders and consequently improving patient outcomes and enhances life quality.

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3 full-factorial design. Size, morphology, zeta potential, permeation, and release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in gel using poloxamer and Carbopol 934P. Liposomal gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). pharmacokinetic examination of payload from liposomal gel displayed higher concentration in brain ( of 93.50 ng/mL). The liposomal nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.

The aim of this study was to load 4-farnesyloxycoumarin (4-FLC) in nanoliposomes (4-FLC-LNPs) and evaluate its anti-cancer and anti-metastatic effects. 4-FLC-LNPs were synthesized using a combination of lecithin-cholesterol-polyethylene glycol. The physicochemical properties were evaluated using DLS, FTIR, and microscopy methods. The toxicity against breast cancer (MCF-7), prostate cancer (PS3), pancreatic cancer (PANC), gastric cancer (AGS), and normal cell lines (HUVEC) was evaluated using the MTT assay. Fluorescent staining and flow cytometry were used to assess the occurrence of apoptosis. Molecular analysis methods were used to study the apoptosis and metastasis effects of these nanoliposomes. The antioxidant power of 4-FLC-LNPs was measured using the ABTS and DPPH free radicals methods. 4-FLC-LNPs exhibit a spherical morphology, with an average size of 57.43 nm, a polydispersity index of 0.29, and a zeta potential of -31.4 mV. They demonstrate an encapsulation efficiency of 82.4% for 4-FLC. The IC50 value of 4-FLC-LNPs against the breast cancer cell line was reported as the most sensitive, at approximately 60 μg/mL. ABTS and DPPH results were reported at approximately 30 µg/mL. The inductive effects of nanoliposomes on the apoptosis process were confirmed by an increase in the number of apoptotic cells, as well as the arrest of cells in various phases of cell growth. The increased expression of BAX and decreased expression of Bcl-2, MMP-2, and MMP-9 confirmed the pro-apoptotic and anti-metastatic effects of 4-FLC-LNPs. These finding validate the therapeutic potential of 4-FLC-LNPs, which may be utilized in preclinical studies.

Vesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A (PLA) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities.

Carnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting. In the present study, the development and characterization of new liposomal formulations loaded with carnosine are described. Nanoliposomes, produced through Thin-Layer Hydration followed by Extrusion method, were first investigated for their physicochemical stability. Photon correlation spectroscopy and electrophoretic light scattering, assessing the stability of the formulations, showed a strong homogeneity-oriented tendency for up to two months. Particle size, polydispersity index, and zeta potential were determined through dynamic light scattering and electrophoretic light scattering, demonstrating an almost neutral charge of the formulation and an effective encapsulation of carnosine. The morphology assessment performed via scanning electron microscopy showed good conformity and polydispersity. Differential scanning calorimetry measurements suggest the ability of carnosine to stabilize the large unilamellar vesicles. Lastly, the newly developed carnosine-loaded liposomal formulations also showed a good safety profile in human microglia.

Giant liposomes, or giant unilamellar vesicles (GUVs), have been utilized as cell-size bioreactors to replicate the physical and chemical properties of biological cells. However, conventional methods for preparing GUVs typically lack precise control over their size. Several research groups have recently developed microfluidic techniques to create monodisperse GUVs by generating water-in-oil-in-water (W/O/W) droplets with a thin oil layer that subsequently transform into GUVs. However, the formation of a thin oil shell requires the intricate control of the flow rate, which can be both challenging and unstable. In this study, we investigated the design of a two-step flow-focusing microfluidic channel to produce stable W/O/W droplets. These droplets underwent substantial oil layer reduction through spontaneous removal by fluidic shear forces. Consequently, the majority of the oil layer in the W/O/W droplets was reduced, improving uniformity of GUVs.

This study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential.

Naringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and -27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin ( = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin.

Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function ( = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC = 0.58 μM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC = 1.00 μM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.

To enhance cytoplasmic delivery efficiency, pH-sensitive liposomes (PSL) have been proposed as a novel strategy. To facilitate clinical translation, this study aims to understand the impact of both size and pH-sensitivity on cellular uptake pathways, intracellular trafficking and pharmacokinetics of liposomes. The large liposomes (130-160 nm) were prepared using thin-film hydration method, while small liposomes (∼60 nm) were fabricated using microfluidics, for both PSL and non-pH-sensitive liposomes (NPSL). Cellular uptake pathways and intracellular trafficking was investigated through confocal imaging with aid of various endocytosis inhibitors. Intracellular gemcitabine delivery by various liposomal formulations was quantified using HPLC, and the cytotoxicity was assessed via cell viability assays. Pharmacokinetics of gemcitabine loaded in various liposomes was evaluated in rats following intravenous administration. Larger liposomes had a higher loading capacity for hydrophilic gemcitabine (7% vs 4%). Small PSL exhibited superior cellular uptake compared to large PSL or NPSLs. Moreover, the alkalization of endosomes significantly attenuated the cellular uptake of PSL. Large liposomes (PSL and NPSL) predominantly entered cells via clathrin-dependent pathway, whereas small liposomes partially utilized caveolae-dependent pathway. However, the long circulation of the liposomes, as measured by the encapsulated gemcitabine, was compromised by both pH-sensitivity and size reduction (9.5 h vs 5.3 h). Despite this drawback, our results indicate that small PSL holds promise as vectors for the next generation of liposomal nanomedicine, owing to their superior cytoplasmic delivery efficiency.

The high complexity of biological membranes has driven the development and application of a wide range of model membrane systems. Among these models, liposomes are extensively used because of their versatility in mimicking cellular membranes with a wide range of lipid compositions. However, the accurate quantification of lipid components, such as sterols, within these models remains a critical requirement for validation, data interpretation, and comparison. Here, we present a reliable and sensitive colorimetric assay using the Zak color reaction, which we have specifically adapted for the quantification of sterols at the micro-scale level. The assay was evaluated using cholesterol, ergosterol, and sitosterol standards, reflecting the diversity of sterol species across organisms. The reaction mechanism involves the dehydration of sterols to form carbonium ions, which are oxidized to form various enylic carbonium ions with specific absorption peaks. Due to the different chemical structures of cholesterol, ergosterol, and sitosterol, the resulting spectra show that the colored reaction products are formed in different proportions. The stability and interconversion of these species over time were analyzed. Cholesterol and sitosterol showed a clear peak at 555 nm, while ergosterol had prominent peaks at shorter wavelengths. Sterol assays on liposomal preparations showed accurate sterol incorporation with minimal loss during processing steps. These results demonstrate that this assay provides a robust and accurate measurement of sterol content in large unilamellar vesicles, making it a valuable tool for liposomal studies.

Taxane drugs are clinically used for the treatment of many types of cancers due to their excellent antitumor effects. However, the surfactants contained in the injections currently used in the clinic may have serious toxic side effects on the organism, making it necessary to develop new dosage forms. Cationic liposomes have been widely used in antitumor research because of their advantage of preferentially targeting tumor neovascularization, but antitumor by targeting tumor vasculature alone does not necessarily provide good results. Malignant tumors represent complex ecosystems, tumor-associated macrophages (TAMs) and tumor endothelial cells (TECs) in the tumor microenvironment play crucial roles in tumor growth. Therefore, given the ability to achieve active targeting of TAMs and TECs by using sialic acid (SA) as a targeting material, the potential of cationic nanoformulations to preferentially target neovascularization at the tumor site, and the excellent antitumor effects of the taxane drugs docetaxel (DOC), in the present study, sialic acid-cholesterol coupling (SA-CH) was selected as a targeting material to prepare a DOC cationic liposome (DOC-SAL) for tumor therapy. The results of the study showed that DOC-SAL had the strongest drug accumulation in tumor tissues compared with the common DOC formulations, and was able to effectively reduce the colonization of TAMs, inhibit the proliferation of tumor cells, and have the best tumor-suppressing effect. In addition, DOC-SAL was able to improve the internal microenvironment of tumors by modulating cytokines. In summary, this drug delivery system has good anti-tumor effects and provides a new option for tumor therapy.

In this study, it was aimed to analyze the effects of liposomes on the dyeing of polyacrylonitrile fabrics. For this purpose, firstly liposome synthesis was carried out, and then liposome production was confirmed by Fourier transform infrared spectroscopy analysis. Additionally, zeta potential measurements were carried out to see whether stable structures were formed. Then, a selected basic dye was encapsulated with a liposome and the possibilities of using these capsules as alternative to retarders in the dyeing of polyacrylonitrile fabrics were examined. According to results obtained, it can be said that the 1% solution of synthesized liposomes creates a more stable suspension with a polydispersity index of 0.472 and the average particle size of 165.2 nm. On the other hand, it has been revealed that if 1% liposome is used in dyeing, a kind of retarder effect can be achieved in the dyeing of polyacrylonitrile fabrics. Moreover, it can be said that the decrease in color efficiency, that is, the loss of yield, caused by the use of liposome at the end of dyeing is lower compared to the retarder. This is also a very important issue, because a good retarder is expected to slow down the dye uptake, but not reduce the dye intake too much at the end of the dyeing. Dyeing levelness (%) was found to be 96.1, 97.4, and 97.1 for dyeings without auxiliary, with 1% cationic retarder and with 1% liposome, respectively. Beyond this, no significant difference was observed in terms of fastness of dyeing.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 2 factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the skin permeation and deposition. Finally, it was subjected to an array of tests, namely Draize test, histopathology, , edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (-55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm), nociception inhibition (77%) and (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm, 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.