Neuroprotective efficiency of celecoxib vesicular bilosomes for the management of lipopolysaccharide-induced Alzheimer in mice employing 23 full factorial design.

The aim of this study was to develop and evaluate bilosomes loaded with Celecoxib (CXB) for the efficient treatment of Alzheimer. The thin-film hydration approach was utilized in the formulation of CXB bilosomes (CXB-BLs). The study used a 23-factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: bile salt type (X1), medication amount (X2), and lipid-bile salt ratio (X3). The dependent responses included entrapment efficiency (Y1: EE %), particle size (Y2: PS), and zeta potential (Y3: ZP). The formulation factors were statistically optimized using the Design-Expert® program. The vesicles demonstrated remarkable CXB encapsulation efficiency, ranging from 94.16 ± 1.91 to 98.38 ± 0.85%. The vesicle sizes ranged from 241.8 ± 6.74 to 352 ± 2.34 nm. The produced formulations have high negative zeta potential values, indicating strong stability. Transmission electron microscopy (TEM) revealed that the optimized vesicles had a spherical form. CXB release from BLs was biphasic, with the release pattern following Higuchi's model. In vivo studies confirmed the efficiency of CXB-BLs in management of lipopolysaccharide-induced Alzheimer as CXB-BLs ameliorated cognitive dysfunction, decreased acetylcholinesterase (AChE), and inhibited neuro-inflammation and neuro-degeneration through reducing Toll-like receptor (TLR4), and Interleukin-1ß (IL-1ß) levels. The findings suggested that the created CXB-BLs could be a potential drug delivery strategy for Alzheimer's treatment.

Intranasal bilosomes in thermosensitive hydrogel: advancing desvenlafaxine succinate delivery for depression management.

Depression, the second biggest cause of disability worldwide, is widespread. Many antidepressant medications, including Desvenlafaxine Succinate (D.V.S.), function by elevating neurotransmitter levels at the synapse through the inhibition of reabsorption by neurons. However, the effectiveness of these treatments is often limited by their inability to reach the brain using conventional administration methods. Bilosome-stabilized nanovesicles containing bile salts have drawn much interest because of their adaptability and versatility in various applications. This study aimed to address this issue by formulating intranasal bilosomes incorporated into a mucoadhesive in situ gel to deliver D.V.S. directly to the brain for depression treatment. The desvenlafaxine-loaded bilosomes were developed using a thin film hydration method based on the l-optimal design. They were intended to provide a more convenient route of administration for antidepressants, enhancing bioavailability and brain targeting through intranasal delivery. The study assessed the optimized bilosomes for particle size (311.21 ± 0.42 nm), Zeta potential (-37.35 ± 0.43)and encapsulation efficiency (99.53 ± 0.41%) and further evaluated them in ex vivo and in vivo pharmacokinetics studies. Pharmacokinetic data reveal enhanced brain uptake compared to a free drug. A statistically optimized bilosome formulation was determined. The intranasal administration of mucoadhesive in situ gel containing desvenlafaxine succinate-loaded bilosomes facilitated direct nose-to-brain drug delivery, improving brain bioavailability.

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems.

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract.

The Exploitation of Sodium Deoxycholate-Stabilized Nano-Vesicular Gel for Ameliorating the Antipsychotic Efficiency of Sulpiride.

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 33 Box-Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.

Bile salt-enriched vs. non-enriched nanoparticles: comparison of their physicochemical characteristics and release pattern.

Bile salts were first used in the preparation of nanoparticles due to their stabilizing effects. As time went by, they attracted much attention and were increasingly employed in fabricating nanoparticles. It is well accepted that the physicochemical properties of nanoparticles are influential factors in their permeation, distribution, elimination and degree of effectiveness as well as toxicity. The review of articles shows that the use of bile salts in the structure of nanocarriers may cause significant changes in their physicochemical properties. Hence, having information about the effect of bile salts on the properties of nanoparticles could be valuable in the design of optimal carriers. Herein, we review studies in which bile salts were used in preparing liposomes, niosomes and other nanocarriers. Furthermore, the effects of bile salts on entrapment efficiency, particle size, polydispersity index, zeta potential, release profile and stability of nanoparticles are pointed out. Finally, we debate how to take advantage of bile salts potential for preparing desirable nanocarriers.

Enhanced Oral Bioavailability of Progesterone in Bilosome Formulation: Fabrication, Statistical Optimization, and Pharmacokinetic Study.

Progesterone, a female sex steroid hormone, is highly lipophilic, leading to poor oral bioavailability. This study aimed to develop a progesterone bilosome system to enhance its oral bioavailability and retain it longer in the body. Progesterone vesicles were formulated with bile salts by thin film hydration method to prevent enzymatic and bile acid degradation. The Box-Behnken experimental design was used to statistically optimize progesterone bilosomes by checking the effect of phosphatidylcholine, cholesterol, and sodium deoxycholate on vesicle size, zeta potential, and entrapment efficiency. The optimum batch showed 239.5 nm vesicle size, -28.2 mV zeta potential and 84.08% entrapment efficiency, respectively, which were significantly affected by phosphatidylcholine and cholesterol concentration. The successful incorporation of progesterone in the system was evident from ATR-FTIR analysis that revealed no sharp progesterone peaks in bilosomes. TEM analysis confirmed the spherical structure and uniform bilosome vesicles. Furthermore, the in vitro drug release of progesterone bilosomes revealed a sustained pattern exhibiting 90% drug release in 48 h. The pharmacokinetic study in female ovariectomized Wistar rats confirmed the 4.287- and 9.75-fold enhanced oral bioavailability of the progesterone bilosomes than marketed capsules and progesterone API, respectively. Therefore, progesterone bilosome formulation can be further explored for improved oral administration in chronic treatments.

Cross-Linked Alginate Dialdehyde/Chitosan Hydrogel Encompassing Curcumin-Loaded Bilosomes for Enhanced Wound Healing Activity.

The current study aimed to fabricate curcumin-loaded bilosomal hydrogel for topical wound healing purposes, hence alleviating the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated via the thin film hydration technique using cholesterol, Span® 60, and two different types of bile salts (sodium deoxycholate or sodium cholate). Bilosomes were verified for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and in vitro drug release besides their morphological features. The optimum formulation was composed of cholesterol/Span® 60 (molar ratio 1:10 w/w) and 5 mg of sodium deoxycholate. This optimum formulation was composed of a PS of 246.25 ± 11.85 nm, PDI of 0.339 ± 0.030, ZP of -36.75 ± 0.14 mv, EE% of 93.32% ± 0.40, and the highest percent of drug released over three days (96.23% ± 0.02). The optimum bilosomal formulation was loaded into alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel was tested for its water uptake capacity, in vitro drug release, and in vivo studies on male Albino rats. The results showed that the loaded hydrogel possessed a high-water uptake percent at the four-week time point (729.50% ± 43.13) before it started to disintegrate gradually; in addition, it showed sustained drug release for five days (≈100%). In vivo animal testing and histopathological studies supported the superiority of the curcumin-loaded bilosomal hydrogel in wound healing compared to the curcumin dispersion and plain hydrogel, where there was a complete wound closure attained after the three-week period with a proper healing mechanism. Finally, it was concluded that curcumin-loaded bilosomal hydrogel offered a robust, efficient, and user-friendly dosage form for wound healing.

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG.

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt-enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.

Vesicle-Encapsulated Rolipram (PDE4 Inhibitor) and Its Anticancer Activity.

Vesicular carriers of drugs are popular for specific targeting and delivery. The most popular vesicles among these are liposomes. However, they suffer from some inherent limitations. In this work, alternative vesicles with enhanced stability, i.e., niosomes and bilosomes have been prepared, characterized, and their delivery efficiency studied. Bilosomes have the additional advantage of being able to withstand the harsh environment of the gastrointestinal tract (GIT). The taurine-derived bile salt (NaTC) was incorporated into the bilosome bilayer. The inspiration behind NaTC insertion is the recent reports on antiaging action and immune function of taurine. Fluorescence probing was used to study the vesicle environment. The entrapment and subsequent release of the important cAMP-specific PDE4 inhibitor/drug Rolipram, which has antibreast cancer properties, was assessed on the breast cancer cell line MCF-7. Rolipram has important therapeutic applications, one of the most significant in recent times being the treatment of Covid-19-triggered pneumonia and cytokine storms. As for cancer chemotherapy, the localization of drug, targeted delivery, and sustained release are extremely important issues, and it seemed worthwhile to explore the potential of the bilosomes and niosomes to entrap and release Rolipram. The important finding is that niosomes perform much better than bilosomes in the hormone-responsive breast cancer mileau MCF-7. Moreover, there was a 4-fold decrease in the IC50 of Rolipram encapsulated in niosomes compared to Rolipram alone. On the other hand, bilosome-encapsulated Rolipram shows higher IC50 value. The results can be further understood by molecular docking studies.

Unlocking the Potential of Bilosomes and Modified Bilosomes: a Comprehensive Journey into Advanced Drug Delivery Trends.

Vesicular drug delivery systems have revolutionized the pharmaceutical field, offering a promising path for achieving targeted and sustained drug delivery. The oral, transdermal, and ocular routes of administration offer optimal ease in attaining desired therapeutic outcomes. However, conventional treatment strategies are all plagued with several challenges, such as poor skin permeability, ocular barriers, and gastrointestinal (GIT) degradation leading to vesicular disruption with the release of the encapsulated drug before reaching the targeted site of action. In recent years, bilosomes-stabilized nanovesicles containing bile salts have received considerable attention due to their versatility and adaptability for diverse applications. These bilayered vesicles enhance the solubility of lipophilic drugs and improve formulation stability in the gastrointestinal tract. They exhibit ultra-deformable properties, improving stratum corneum permeability, making them ideal candidates for oral and transdermal drug delivery. In addition, bilosomes find utility in topical drug delivery, making them applicable for ocular administration. Over the past decade, extensive research has highlighted bilosomes' potential as superior vesicular carriers surpassing liposomes and niosomes. Advances in this field have led to the development of modified bilosomes, such as probilosomes and surface-modified bilosomes, further enhancing their capabilities and therapeutic potential. Thus, the present review provides a comprehensive summary of bilosomes, modified bilosomes, surface modifications with their mechanism of action, formulation components, preparation methods, patents, and a wide array of recent pharmaceutical applications in oral, transdermal, and ocular drug delivery. The enhanced properties of bilosomes offer promising prospects for targeted and effective drug delivery, providing potential solutions for addressing various therapeutic challenges.

Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells.

Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Therefore, this study aimed to enhance the anti-proliferative activity of COST in LS174T colon cancer cells through its inclusion in bilosomal nanoformulation (COST-BILs). The optimized BIL formula contained cholesterol and Span-85 in a molar ratio of 1:5 as well as bile salt at a molar concentration of 0.5 mM, with entrapment efficiency of 63.4 ± 3.59 % and particle size of 119.7 ± 3.63 nm. The optimized COST-BILs showed a potent cytotoxic effect against LS174T cells with an IC50 of 6.20 µM; meanwhile, raw COST had an IC50 of 15.78 µM. Safety and relative selectivity were confirmed in the normal human colonic epithelial cells (HCoEpC). Cell cycle analysis indicated that both raw COST and COST-BILs significantly increased the fraction of LS174T cells in the sub-G1 phase. This was accompanied by a significant enhancement of early, late, and total apoptosis, as indicated by annexin-V staining. In addition, COST-BILs exhibited more potent activity in up-regulating CASP3, TP53, and BAX, and in down-regulating the expression of BCL2 mRNA as compared to raw COST. Further, the prepared formula enhanced the release of cytochrome C as well as the generation of reactive oxygen species (ROS) and reduced the integrity of mitochondrial membranes. In conclusion, the loading of COST on BILs significantly enhances its pro-apoptotic activity in LS174T cells.

Bilosomes as Nanocarriers for the Drug and Vaccine Delivery against Gastrointestinal Infections: Opportunities and Challenges.

The gastrointestinal tract (GIT) environment has an intricate and complex nature, limiting drugs' stability, oral bioavailability, and adsorption. Additionally, due to the drugs' toxicity and side effects, renders are continuously seeking novel delivery systems. Lipid-based drug delivery vesicles have shown various loading capacities and high stability levels within the GIT. Indeed, most vesicular platforms fail to efficiently deliver drugs toward this route. Notably, the stability of vesicular constructs is different based on the different ingredients added. A low GIT stability of liposomes and niosomes and a low loading capacity of exosomes in drug delivery have been described in the literature. Bilosomes are nonionic, amphiphilic, flexible surfactant vehicles that contain bile salts for the improvement of drug and vaccine delivery. The bilosomes' stability and plasticity in the GIT facilitate the efficient carriage of drugs (such as antimicrobial, antiparasitic, and antifungal drugs), vaccines, and bioactive compounds to treat infectious agents. Considering the intricate and harsh nature of the GIT, bilosomal formulations of oral substances have a remarkably enhanced delivery efficiency, overcoming these conditions. This review aimed to evaluate the potential of bilosomes as drug delivery platforms for antimicrobial, antiviral, antifungal, and antiparasitic GIT-associated drugs and vaccines.

Investigating the superiority of chitosan/D-alpha-tocopheryl polyethylene glycol succinate binary coated bilosomes in promoting the cellular uptake and anti-SARS-CoV-2 activity of polyphenolic herbal drug candidate.

The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 23 full factorial designs to improve solubility and intestinal permeability of CUR, hence boosting its anti-SARS-CoV-2 activity. Eight experimental runs were attained considering three independent variables: soybean phosphatidylcholine amount (mg) (SPC amount), bile salt amount (mg) (BS amount), and TPGS amount (mg). The optimum formula (F4) exhibited EE % (88.5 ± 2.4 %), PS (181.5 ± 21.6 nm), and ZP (-34.5 ± 3.7 mV) with desirability value = 0.739 was picked as an optimum formula. Furthermore, the optimum formula (F4) was extra coated with chitosan (CS) to improve permeability and anti-SAR-CoV-2 activity. Caco-2 cell uptake after 2 hr revealed the superiority of CS-F4 and F4 by 6 and 5 folds relative to CUR dispersion, respectively. Furthermore, CS-F4 exhibited a significantly higher anti-SARS-CoV-2 activity with IC50 (0.24 µg/ml) by 8.3 times than F4 (1.99 µg/ml). Besides, the mechanistic study demonstrated that the two formulae imparted antiviral activity by inhibiting the spike protein by virucidal potentialities. In addition, the conducted molecular docking and MD simulations towards the SARS-CoV-2 Mpro enzyme confirmed the interaction of CUR with key residues of the virus enzymes. Based on the preceded, CS-F4 could be assumed to be used to effectively eradicate SARS-CoV-2 infection.

Breaking barriers: bilosomes gel potentials to pave the way for transdermal breast cancer treatment with Tamoxifen.

OBJECTIVE: Breast cancer affects women globally, regardless of age or location. On the other hand, Tamoxifen (TXN), a class II biopharmaceutical drug is acting as a prophylactic/treating agent for women at risk of and/or with hormone receptor-positive breast cancer. However, its oral administration has life-threatening side effects, which have led researchers to investigate alternative delivery methods. One such method is transdermal drug delivery utilizing bile salts as penetration enhancers, aka Bilosomes. METHODS: Bilosomes formulations were optimized statistically for the outcome of vesicle shape, size, and entrapment efficiency using two types of bile, i.e. sodium taurocholate and sodium cholate. These bilosomes were then loaded into HPMC base gel and further characterized for their morphology, drug content, pH, viscosity, spreadability and eventually ex-vivo skin penetration and deposition studies. RESULTS: Findings showed that sodium cholate has superiority as a penetration enhancer over sodium taurocholate in terms of morphological characterizes, zeta potential, and cumulative amounts of tamoxifen permeated per unit area (15.13 ± 0.71 µg/cm2 and 6.51 ± 0.6 µg/cm2 respectively). In fact, bilosomes designed with sodium cholate provided around 9 folds of skin deposition compared to TXN non-bilosomal gel. CONCLUSION: Bilosomes gels could be a promising option for locally delivering tamoxifen to the breast through the skin, offering an encouraging transdermal solution.

Chrysin loaded bilosomes improve the hepatoprotective effects of chrysin against CCl4 induced hepatotoxicity in mice.

In the present work, chrysin loaded bilosomes were formulated, characterized and evaluated to enhance the hepatoprotective activity of drug. Accordingly, chrysin loaded bilosomes were prepared by applying the thin film hydration method; also, fractional factorial design was used to optimize the production conditions of nanoformulations. The prepared formulations were subjected to different methods of characterization; then the hepatoprotective activity of the optimized one was evaluated in the CCl4 hepatointoxicated mice model. Optimized chrysin loaded bilosomes showed a spherical shape with a particle size of 232.97 ± 23 nm, the polydispersity index of 0.35 ± 0.01, the zeta potential of -44.5 ± 1.27 mv, the entrapment efficiency of 96.77 ± 0.18%, the drug loading % of 6.46 ± 0.01 and the release efficiency of 42.25 ± 1.04 during 48 h. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay demonstrated the superiority of the anti-oxidant potential of chrysin loaded bilosomes, as compared to pure chrysin. This was in agreement with histopathological investigations, showing significant improvement in serum hepatic biomarkers of CCl4 intoxicated mice treated with chrysin loaded bilosomes, as compared with free chrysin. These results, thus, showed the potential use of bilosomes to enhance the hepatoprotective activity of chrysin via oral administration.

Novel vesicular bilosomal delivery systems for dermal/transdermal applications.

The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.

Exploring Penetration Ability of Carbonic Anhydrase Inhibitor-Loaded Ultradeformable Bilosome for Effective Ocular Application.

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04 nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10 h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6 h and trans-corneal permeability of 8.78 ± 0.14 cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.

Brij® integrated bilosomes for improving the transdermal delivery of niflumic acid for effective treatment of osteoarthritis: In vitro characterization, ex vivo permeability assessment, and in vivo study.

Bilosomes are innovative vesicular carriers containing bile salt with a non-ionic surfactant. Being highly flexible, bilosomes can squeeze themselves through the skin carrying the drug to the action site and improving its skin penetration. The objective of this research was to encapsulate niflumic acid (NA), a non-steroidal anti-inflammatory drug into Brij® integrated bilosomes (BIBs) for effective treatment of osteoarthritis through transdermal delivery. BIBs were formulated using 100 mg of Span 20 with different amounts of sodium cholate (NaC), sodium taurocholate (NaTC), or sodium glycocholate (NaGC) as bile salt, with the addition of 5 mg of Brij-93 or Brij-35. BIBs were prepared utilizing ethanol injection method with the application of (31 × 22) complete factorial design using Design-Expert® software. The optimal BIBs formulation determined was (B5) which contains 5 mg of NaTC used as bile salt and 5 mg of Brij-93. B5 exhibited entrapment efficiency% = 95.21 ± 0.00%, particle size = 373.05 ± 0.07 nm, polydispersity index = 0.27 ± 0.01, and zeta potential = -32.00 ± 0.00 mV. It also had a high elasticity with a spherical shape. B5 gel displayed a sustained release profile with a significantly 2.3 folds' higher drug permeation percent across rat skin than that permeated from NA gel. Moreover, in vivo anti-osteoarthritic and histopathological studies assured the efficacy and safety of B5 gel and its superiority over NA gel. Generally, the outcomes confirmed the great efficacy of NA loaded BIBs for the topical treatment of osteoarthritis.

Experimental design of D-α-tocopherol polyethylene glycol 1000 succinate stabilized bile salt based Nano-vesicles for improved cytotoxicity and bioavailability of colchicine binding site inhibitor Candidates: In Vitro, in silico, and pharmacokinetic studies.

Nowadays, conventional anticancer therapy suffers many pitfalls, including drastic side effects and limited therapeutic efficacy resulting from diminished oral bioavailability. So, in an attempt to enhance their poor solubility and oral bioavailability along with the cytotoxic activity, the developed lead compounds (C1 and C2) were loaded in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified vesicles adopting thin film hydration technique. The formulations of the aforementioned candidates (F1 and F2, respectively) were elected as the optimum formula with desirability values of 0.701 and 0.618, respectively. Furthermore, an outstanding enhancement in the drug's cytotoxic activity against different cancer cell lines (MCF-7, HepG-2, MDA-MB-321, A375, and MGC-803) after being included in the nano-TPGS-modified optimum formula was noticed relative to the unformulated compounds. The formula F1 showed the best cytotoxic activities against HepG-2 with an IC50 = 3 µM. Furthermore, regarding MCF-7, F1 was shown to be the most potent and protective among all the tested formulations with an IC50 = 6 µM. Besides, F1 exerted the best caspase 3/7 activity stimulation (around a 5-folds increase) compared to control in the MCF-7 cell line. Notably, it was disclosedthat both C1 and C2 induced cell cycle arrest at the resting S growth phase. Moreover, C1 and C2 decreased tubulin concentrations by approximately 2-folds and 6-folds, respectively. Meanwhile, the conducted molecular docking studies ensure the eligible binding affinities of the assessed compounds. Besides, MD simulations were performed for 1000 ns to confirm the docking results and study the exact behavior of the target candidates (C1 and C2) toward the CBS.