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.

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.

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.

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.

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.

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.

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.

Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice.

BACKGROUND: The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD. RESULTS: DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways CONCLUSION: DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.

Fabrication of Highly Deformable Bilosomes for Enhancing the Topical Delivery of Terconazole: In Vitro Characterization, Microbiological Evaluation, and In Vivo Skin Deposition Study.

The current study aimed to load terconazole (TCZ), an antifungal agent with low permeability characteristics, into highly deformable bilosomes (HBs) for augmenting its topical delivery. HBs contain edge activator in addition to the constituents of traditional bilosomes (Span 60, cholesterol, and bile salts). More elasticity is provided to the membrane of vesicles by the existence of edge activator and is expected to increase the topical permeation of TCZ. HBs were formulated using ethanol injection technique based on 24 complete factorial design to inspect the impact of various formulation variables (bile salt type and amount, edge activator type, and sonication time) on HBs characteristics (entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP)). The optimum formula (HB14) was decided based on Design-Expert® software and was utilized for further explorations. HB14 exhibited EE% = 84.25 ± 0.49%, PS = 400.10 ± 1.69 nm, PDI = 0.23 ± 0.01, and ZP = - 56.20 ± 0.00 mV. HB14 showed spherical vesicles with higher deformability index (9.94 ± 1.91 g) compared to traditional bilosomal formula (3.49 ± 0.49 g). Furthermore, HB14 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition studies revealed superior TCZ deposition inside the skin from HB14 compared to traditional bilosomal formula and TCZ suspension. Moreover, histopathological examination in rats assured the safety of HB14 for topical use. Concisely, the obtained outcomes confirmed the pronounced efficacy of HBs for topical delivery of TCZ.

Bioactive Apigenin loaded oral nano bilosomes: Formulation optimization to preclinical assessment.

AIM: Diabetic (type-2) is a metabolic disease characterized by increased blood glucose level from the normal level. In the present study, apigenin (AG) loaded lipid vesicles (bilosomes: BIL) was prepared, optimized and evaluated for the oral therapeutic efficacy. EXPERIMENTAL: AG-BIL was prepared by a thin-film evaporation method using cholesterol, span 60 and sodium deoxycholate. The prepared formulation was optimized by 3-factor and 3-level Box-Behnken design using particle size, entrapment efficiency and drug release as a response. The selected formulation further evaluated for ex-vivo permeation, in vivo pharmacokinetic and pharmacodynamics study. RESULTS: The optimized AG bilosomes (AG-BILopt) has shown the vesicle size 183.25 ± 2.43 nm, entrapment efficiency 81.67 ± 4.87%. TEM image showed a spherical shape vesicle with sharp boundaries. The drug release study revealed a significant enhancement in AG release (79.45 ± 4.18%) from AG-BILopt as compared to free AG-dispersion (25.47 ± 3.64%). The permeation and pharmacokinetic studies result revealed 4.49 times higher flux and 4.67 folds higher AUC0-t than free AG-dispersion. The antidiabetic activity results showed significant (P < 0.05) enhancement in therapeutic efficacy than free AG-dispersion. The results also showed marked improvement in biochemical parameters. CONCLUSION: Our findings suggested, the prepared apigenin loaded bilosomes was found to be an efficient delivery in the therapeutic efficacy in diabetes.

Bilosomes as a novel carrier for the cutaneous delivery for dapsone as a potential treatment of acne: preparation, characterization and in vivo skin deposition assay.

In our study, the potential of bilosomes as novel vesicular carrier for the cutaneous delivery of the sulphone compound, Dapsone, for topical treatment of acne was investigated. The effect of different formulation variables (type and concentration of bile salt, and molar ratio of Span 60:cholesterol) on the properties of DPS-loaded bilosomes was investigated using a full factorial design. Design Expert software was used for data analysis and optimization of DPS-loaded bilosomes. The optimized bilosomes, chosen on the basis of their superior properties giving maximum entrapment, in vitro release after different time intervals and RE% with minimum vesicle size. Results showed that the bilosome system prepared using Span® 60: Cholesterol (5:1) and containing 0.25 M sodium deoxycholate as the bile salt was found to obey these criteria, with a desirability value of 0.637. Therefore, this system was chosen for further assessment for its morphological properties, zeta potential, thermal analysis using differential scanning calorimetry and X-ray diffractometry. Results revealed that the chosen bilosomes were spherical in shape with no aggregation, and contained DPS in a molecularly dispersed amorphous form. Finally, the capability of the optimized DPS-loaded bilosomes to deliver DPS through rat skin layers will be investigated and compared with that of DPS alcoholic solution. Results showed that the amounts of DPS retained in the skin treated with DPS-loaded bilosomes, and DPS alcoholic solution after 24 h were found to be 170.57 ± 55.12 and 120.24 ± 10.7 µg/mL, respectively, representing about 1.5-fold higher drug retained in the bilosomes-treated skin. Finally, the safety and the tolerability of the prepared bilosomes were assessed using histopathological examination, and revealed that the control untreated skin sections and skin sections treated with DPS-loaded bilosomes showed normal histological structures characterized by absence of defects or inflammation. Such results can be considered a good addition in the field of pharmaceutical drug delivery for effective topical therapy of acne.

Investigating superiority of novel bilosomes over niosomes in the transdermal delivery of diacerein: in vitro characterization, ex vivo permeation and in vivo skin deposition study.

Skin is considered the most accessible organ of the body because of its underlying capillary network. However, stratum corneum (SC), the upper most layer of skin, represents major diffusional barrier for most drugs. Hence, the use of edge activators (EAs) in designing novel elastic vesicles is hypothesized to impart their lipid bilayer with ultra-flexibility to trespass SC by high self-optimizing deformability. To confirm this hypothesis, this work aimed at developing novel bilosomes by modulating conventional niosomal composition using different bile salts as EAs and investigating their superiority over niosomes for transdermal delivery of diacerein (DCN), as model drug. Bilosomes were prepared by thin film hydration (TFH) technique according to full 31.22 factorial design to select the optimal formulation using Design-Expert® software. The optimal bilosomes (B6) showed nanosized vesicles (301.65 ± 17.32 nm) and 100.00 ± 0.00 % entrapment efficiency. Ex vivo permeation studies and in vivo evaluation revealed that B6 exhibited superior permeation and drug retention capacity compared to the conventional niosomal formulation and drug suspension. Furthermore, B6 was subjected to in vivo histopathological study using male Wistar rats which ensured its safety for topical application. Overall, the results confirmed the hypothesized superiority of bilosomes over niosomes for enhancing DCN flux across the skin.

Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization.

Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

Transdermal Delivery of Ondansetron Hydrochloride via Bilosomal Systems: In Vitro, Ex Vivo, and In Vivo Characterization Studies.

Ondansetron hydrochloride (OND) is commonly used for management of postoperative and chemotherapeutic-induced nausea and vomiting. It suffers from low bioavailability (60%) and rapid elimination (t1/2; 3-4 h). The current work aimed to develop OND-loaded bilosomes as a promising transdermal delivery system capable of surmount drug limitations. The variables influencing the development of OND-loaded bilosomes and niosomes (18 systems) via the thin film hydration technique were investigated, including surfactant type (Span®60 or Span®80), surfactant/cholesterol molar ratio (7:0, 7:1, or 7:3), and sodium deoxycholate (SDC) concentration (0, 2.5, or 5%, w/v). The systems were characterized for particle size, polydispersity index, zeta potential, drug entrapment efficiency (EE%), and in vitro permeation. Based on factorial analysis (32·21) and calculations of desirability values, six systems were further subjected to ex vivo permeation through excised rat skin, differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and transmission electron microscopy. Histopathological and in vivo permeation studies in rats were conducted on the best achieved system (B6) in comparison to drug solution. Higher desirability values were achieved with Span® 60-based bilosomes, surfactant/cholesterol molar ratio of 7:1, and SDC concentration of 2.5% w/v with respect to small vesicle size, polydispersity index and high zeta potential, EE%, and cumulative drug permeation. OND was dispersed in amorphous state as revealed from DSC and PXRD studies. No marked effect was observed in rat skin following application of B6 system while higher ex vivo and in vivo cumulative permeation profiles were revealed. Bilosomal systems were considered as safe and efficient carriers for the transdermal delivery for OND.

Improved hepatoprotective activity of silymarin via encapsulation in the novel vesicular nanosystem bilosomes.

The main objective of the present work was to formulate, characterize, and evaluate silymarin (SM)-loaded bilosomes, compared to conventional liposomes, aiming at increasing the hepatoprotective activity of the drug. SM-loaded bilosomes were prepared by thin film hydration technique employing soybean phosphatidyl choline (SPC) and different bile salts. After being subjected to different methods of characterization, SM-loaded bilosomes were investigated for their hepatoprotective activity, in CCl4 hepatointoxicated rat model. The developed SM dispersions exhibited an entrapment efficiency ranging from 21.80 ± 2.01 to 84.54 ± 2.51% and a particle size diameter in the nanometric dimensions (413 ± 96.9 to 686.9 ± 62.38 nm), with a negative zeta potential values (<-45 mV). In vitro release study revealed a lower cumulative amount of drug released from the developed formulae, compared to free drug. Ex vivo intestinal uptake study, performed using confocal laser scanning calorimetry, revealed the superiority of bilosomal uptake compared to that of liposomes. In vivo studies revealed an enhanced hepatoprotective effect of SM-loaded bilosomes/liposomes compared to free drug. These results were in good correlation with histopathological examination. These findings support the potential use of bilosomes for improving the hepatoprotective activity of SM via oral administration.

Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration.

The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher (P<0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization. FROM THE CLINICAL EDITOR: This team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization.

Assessment of the antigen-specific antibody response induced by mucosal administration of a GnRH conjugate entrapped in lipid nanoparticles.

Vaccines administered parenterally have been developed against gonadotrophin-releasing hormone (GnRH) for anti-fertility and anti-cancer purposes. The aim of this study was to demonstrate whether mucosal delivery using GnRH immunogens entrapped in lipid nanoparticles (LNP) could induce anti-GnRH antibody titers. Immunogens consisting of KLH (keyhole limpet hemocyanin) conjugated to either GnRH-I or GnRH-III analogues were entrapped in LNP. Loaded non-ionic surfactant vesicles (NISVs) were administered subcutaneously, while nasal delivery was achieved using NISV in xanthan gum and oral delivery using NISV containing deoxycholate (bilosomes). NISV and bilosomes had similar properties: they were spherical, in the nanometre size range, with a slightly negative zeta potential and surface properties that changed with protein loading and inclusion of xanthan gum. Following immunization in female BALB/c mice, systemic antibody responses were similar for both GnRH-I and GnRH-III immunization. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies. FROM THE CLINICAL EDITOR: The main research question addressed in this study was whether mucosal delivery using gonadotrophin-releasing hormone immunogens entrapped in lipid nanoparticles could induce anti-GnRH antibody titers. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies with this approach.

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.