Thin Film Hydration Technique Research Articles

Formulation and evaluation of Lamivudine transferosomal gel

Aim and objective: The aim of the study was to formulate and evaluate Transferosomal gel of lamivudine.
 Method:Lamivudine transferosomes was prepared using thin film hydration method taking span 80, Polyoxyethylene lauryl ether in different proportion. the formulation was characterised by UV spectroscopy, FTIR, in-vitro drug release, gel evaluations.
 Results: Total nine formulations were formulated and optimised formulation F3 showed entrapment efficiency EE (91.17), %CDR (96.12) and small particle size (98.19 nm). SEM of optimized lamivudine Transferosomes appeared as spherical, well identified, unilamellar vesicles. The optimized formulation of Transferosomes was further formulated to gel with Poloxamer 407 gel 0.5%, 1% and 2% w/w ,HPMC k15, Propylene glycol, DMSO. Among these F3 formulation with Poloxamer 407 2%w/w transferosomal gel is the optimised transferosmal gel and showed Spreadability value 6.01±0.12 cm, pH value 5.01 ±0.47. The actual drug content of the Transferosomal gel was found to be 97.29 ±0.66%, which represents good content uniformity. The viscosity of lamivudine Transferosomal gel is found to 5960 ±0.75cps. The percentage drug release for lamivudine Transferosomal gel is 97.31 %. stability studies showed that Transferosomal gel is more stable at 4˚C when compared to other temperatures. The future scope of the study is to perform the In Vivo studies to evaluate the potency of the prepared formulation.
 Keywords: Lamivudine Transferosomal gel, Transferosomes, Topical, Anti-viral drug, Thin Film Hydration Technique.

Formulation and evaluation of Lamivudine transferosomal gel

Aim and objective: The aim of the study was to formulate and evaluate Transferosomal gel of lamivudine.
 Method:Lamivudine transferosomes was prepared using thin film hydration method taking span 80, Polyoxyethylene lauryl ether in different proportion. the formulation was characterised by UV spectroscopy, FTIR, in-vitro drug release, gel evaluations.
 Results: Total nine formulations were formulated and optimised formulation F3 showed entrapment efficiency EE (91.17), %CDR (96.12) and small particle size (98.19 nm). SEM of optimized lamivudine Transferosomes appeared as spherical, well identified, unilamellar vesicles. The optimized formulation of Transferosomes was further formulated to gel with Poloxamer 407 gel 0.5%, 1% and 2% w/w ,HPMC k15, Propylene glycol, DMSO. Among these F3 formulation with Poloxamer 407 2%w/w transferosomal gel is the optimised transferosmal gel and showed Spreadability value 6.01±0.12 cm, pH value 5.01 ±0.47. The actual drug content of the Transferosomal gel was found to be 97.29 ±0.66%, which represents good content uniformity. The viscosity of lamivudine Transferosomal gel is found to 5960 ±0.75cps. The percentage drug release for lamivudine Transferosomal gel is 97.31 %. stability studies showed that Transferosomal gel is more stable at 4˚C when compared to other temperatures. The future scope of the study is to perform the In Vivo studies to evaluate the potency of the prepared formulation.
 Keywords: Lamivudine Transferosomal gel, Transferosomes, Topical, Anti-viral drug, Thin Film Hydration Technique.

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells.

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Development and evaluation of N-acetyl glucosamine-decorated vitamin-E-based micelles incorporating resveratrol for cancer therapy

Treatment of cancerous cells like diseases underwent huge latest advancement scenario treatments with a molecular focus targeted therapy. However, non-specifically approaches through the pharmaceutical phytochemicals help a promising alternative approach for cancers. The present research study was seeking to aim at formulating the Resveratrol (RES) loaded Vitamin-E (Vit.E) micelles to improve their bioavailability and reduce toxicity. Resveratrol is a Phyto origin anticancer constituent, lipophilic in nature, with limited water solubility, resulting in poor oral bioavailability and consequently frequent dosing. Thin-film hydration (solvent casting) technique was employed in the building of RES-loaded Vit.E micelles. Prepared micelles are characterized for various parameters and the findings of in vitro evaluation studies revealed proposed micelles having the particle size of 243.4 (d. nm), polydispersity index (PDI) 0.330, zeta potential (−12.4 mV), percentage of entrapment efficiency (80.57% ± 1.06%), and percentage of drug loading (2.77 ± 1.23%), drug release in vitro (75.96%), haemolytic activity in vitro, and cytotoxicity studies in vitro. Furthermore, DSC and P-XRD analysis demonstrated that RES was effectively encapsulated within Vit.E micelles. Drug release studies revealed that dissolution of drug was improved because of loading into micelles and Transmission electron microscopy (TEM) imaging study confirmed spherically of micelles.

Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies.

The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio-which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic behavior. The surfactants used were of non-ionic nature, of which Tween 80® and Brij 58® were more hydrophilic, while Span 40® and Span 60® were more hydrophobic. Each surfactant has unique innate thermal properties and an affinity towards Pluronic 188. The nanosystems were formulated through mixing the pluronic with the surfactants at three different ratios, namely 90:10, 80:20, and 50:50, using the thin-film hydration technique and keeping the pluronic concentration constant. The physicochemical characteristics of the prepared nanosystems were evaluated using various light scattering techniques, while their thermotropic behavior was characterized via microDSC and high-resolution ultrasound spectroscopy. Microenvironmental parameters were attained through the use of fluorescence spectroscopy, while the cytotoxicity of the nanocarriers was studied in vitro. The results indicate that the combination of Pluronic 188 with the above surfactants was able to produce hybrid homogeneous nanoparticle populations of adequately small diameters. The different surfactants had a clear effect on physicochemical parameters such as the size, hydrodynamic diameter, and polydispersity index of the final formulation. The mixing of surfactants with the pluronic clearly changed its thermotropic behavior and thermal transition temperature (Tm) and highlighted the specific interactions that occurred between the different materials, as well as the effect of increasing the surfactant concentration on inherent polymer characteristics and behavior. The formulated nanosystems were found to be mostly of minimal toxicity. The obtained results demonstrate that the thin-film hydration method can be used for the formulation of pluronic-surfactant hybrid nanoparticles, which in turn exhibit favorable characteristics in terms of their possible use in drug delivery applications. This investigation can be used as a road map for the selection of an appropriate nanosystem as a novel vehicle for drug delivery.

Novel Mucoadhesive Chitosomes as a Platform for Enhanced Oral Bioavailability of Cinnarizine.

Cinnarizine (CIN) is a class II BSC drug, suffering from erratic bioavailability due to its pH-dependent solubility. It has preferential absorption in the stomach. In this study, new chitosan (CS) coated niosomes of CIN (CIN-loaded chitosomes) have been developed to extend the gastric retention and ameliorate CIN oral bioavailability. Various CIN-loaded niosomes were fabricated by thin-film hydration technique and fully characterized. Based on the predetermined criteria of low particle size (PS) and high entrapment efficiency percent (EE%), niosomal formulation F1 was selected and further coated with different CS concentrations. The optimized chitosomal formulation (C2) was evaluated through solid state characterization and mucoadhesive efficiency testing. It was also subjected to cytotoxicity study on Caco-2 cells; besides, in vitro drug release, stability and pharmacokinetic studies were assessed. The optimized chitosomal formulation (C2) exhibited an EE% of 58.30±2.75%, PS of 440 ±13.03 nm, PDI of 0.335±0.21 and ZP of +28.1±0.10 mv. Solid state characterization results revealed the compatibility between the vesicle components and the entrapment of CIN within niosomal vesicles. C2 formulation demonstrated favorable mucoadhesive efficiency. The cytotoxicity study on Caco-2 cells manifested the safety of the optimized chitosomal formulation (C2) over the free drug. Additionally, it displayed a remarkable sustaining of CIN in vitro release up to 8 h and exhibited a good stability at the refrigerated temperature up to 3 months. In vivo pharmacokinetic assessment revealed that the CIN bioavailability from the optimized chitosomal formulation C2 was enhanced by 2.79 and 1.92 folds compared to the free drug and uncoated niosomal formulation F1, respectively. The priority of the chitosomal formulation (C2) over the niosomal one (F1) was also conferred. Novel formulation of chitosan coated niosomes (chitosomes) could be presented as a promising platform to improve the oral bioavailability of drugs with narrow absorption window.

A comparative study on biopharmaceutical function of curcumin and miR-34a by multistimuli-responsive nanoniosome carrier: In-vitro and in-vivo.

This research conducted a comparative study on nanoscaled niosomal structures consisting of Tween-80, Tween-60, cholesterol, and dioleoyl-3-trimethylammonium propane (DOTAP). Thin-film hydration technique was used for the preparation and entrapment of curcumin and miRNA in niosomal formulations for enhancing the stability and delivery rate of the agents. Herein, the influence of Tween-80, Tween-60, cholesterol, and DOTAP on the entrapment efficiency (EE%) of curcumin and the physicochemical properties of the carrier are fully discussed. The optimum engineered formulation resulted in a positive charge of +11.23mV, high EE (100%), smooth surface, spherical shape, small diameter (90nm), and good stability in physiological buffers. Also, an accelerated cellular uptake, as well as drug release in PBS (pH 7.4, 37°C) after 72h, were observed. The cytotoxic activity of curcumin (Cur)/miR-34a-loaded nanoparticles was determined by the MTT assay. The results displayed an improved cytotoxic activity of Cur-niosome towards cancer cells compared to free-dispersed Cur. The uptake of Cur-loaded niosome by A280s and A280cp-1 cancer cell lines faced 2.5 folds drop in the concentration compared to its free form. Generally, Cur-niosome exhibits a significant accumulation of superior anti-cancer properties. Likewise, the cytotoxicity of miR-34a-niosome against tumor cells was higher in comparison with its free form. The anti-cancer effects of the gene/drug delivery were investigated in the 4T1 xenografted Balb/C mouse tumor model. According to the in vitro and in vivo results, gene delivery from the modified niosome nanoparticles was distinctly greater than Cur delivery. Therefore, it was concluded that encapsulation of genes in the nano-niosomal delivery system is a promising procedure for the treatment of cancer cells.

Laser thrombolysis and in vitro release kinetics of tPA encapsulated in chitosan polysulfate-coated nanoliposome

A major challenge in managing coronary artery disease is to find an effective thrombolytic therapy with minimal side effects. Laser thrombolysis is a practical procedure to remove the thrombus from inside blocked arteries, although it can cause embolism and re-occlusion of the vessel. The present study aimed to design a liposome drug delivery system for the controlled release of tissue plasminogen activator (tPA) and delivery of drug system into the thrombus by Nd:YAG laser at a wavelength of 532 nm for the treatment of arterial occlusive diseases. In this study, tPA encapsulated into the chitosan polysulfate-coated liposome (Lip/PSCS-tPA) was fabricated by a thin-film hydration technique. The particle size of Lip/tPA and Lip/PSCS-tPA was 88 and 100 nm, respectively. The release rate of tPA from Lip/PSCS-tPA was measured to be 35 % and 66 % after 24 h and 72 h, respectively. Thrombolysis through the delivery of Lip/PSCS-tPA into the thrombus during the laser irradiation was higher compared to irradiated thrombus without the nanoliposomes. The expression of IL-10 and TNF-α genes was studied by RT-PCR. The level of TNF-α for Lip/PSCS-tPA was lower than that of tPA, which can lead to improved cardiac function. Also, in this study, the thrombus dissolution process was studied using a rat model. After 4 h, the thrombus area in the femoral vein was significantly lower for groups treated with Lip/PSCS-tPA (5 %) compared to the groups treated with tPA alone (45 %). Thus, according to our results, the combination of Lip/PSCS-tPA and laser thrombolysis can be introduced as an appropriate technique for accelerating thrombolysis.

“Employment of PEGylated ultra-deformable transferosomes for transdermal delivery of tapentadol with boosted bioavailability and analgesic activity in post-surgical pain”

The utilization of the proper and safe analgesics was considered a major concern in pain alleviation especially that associated with surgical procedures. Novel analgesics as Tapentadol hydrochloride (TAP) was involved efficiently instead of the common opioids to overcome the subsequent severe and common adverse effects associated with opioids utilization. Unfortunately, the extensive first pass metabolism limits the oral bioavailability of TAP and predisposes to a diminished duration of action, hence larger frequent doses of TAP will be required. Therefore, the target of this study was to lodge TAP into PEGylated transferosomes to boost its transdermal delivery. The PEGylation contemplated to boost both TAP permeability and bioavailability besides offering extra resilience to the vesicles.The impact of diverse variables on the characteristics of the vesicles and distinguishing the optimal formula were implemented adopting 23 factorial experiment via Design Expert® software. The resulted eight formulae were fabricated by thin film hydration technique, additionally they were evaluated based on the findings of entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the optimal one was involved in further assessments.The optimal formula (F8) exhibited spherical vesicles with EE% of 77.9 ± 3.4 %, PS of 150.5 ± 5.33 nm, PDI of 0.47 ± 0.05, ZP of −40.7 ± 4.6 mV and it also revealed greater deformability index (30.9 ± 6.1 g) relative to traditional transferosomes (12.15 ± 2.49 g).In addition, confocal laser scanning microscopy examination affirmed the superior penetration of Rhodamine B (RhB) dye thorough the rat's skin from F8 relative to the dye solution. The safety of F8 was confirmed by histopathological study. Moreover, dermato-kinetic study disclosed that TAP exhibited higher retention within the rat's skin form F8 relative to TAP dispersion. Furthermore, the in vivo pharmacodynamics activities conducted on male rats confirmed the superiority of F8 over the drug dispersion in alleviation the induced pain by IP injection of acetic acid and by formation of paw incisions.Collectively, the credibility of F8 as panel for transdermal delivery of TAP with boosted bioavailability and analgesic activity could be ensured on the basis of the obtained findings.

Tea tree oil nanoliposomes: optimization, characterization, and antibacterial activity against Escherichia coli in vitro and in vivo

The purpose of this study was to formulate tee tree oil nanoliposomes (TTONL) and evaluate its characterization and antibacterial activity. TTONL was prepared by thin film hydration and sonication technique, and the preparation conditions were optimized by Box-behnken response surface method. The characterization (morphology, size, zeta potential, and stability) and antibacterial activity of TTONL against Escherichia coli (E. coli) in vitro and in vivo were evaluated. The optimal preparation conditions for TTONL: lecithin to cholesterol mass ratio of 3.7:1, TTO concentration of 0.5%, and pH of the hydration medium of 7.4, which resulted in a TTONL encapsulation rate of 80.31 ± 0.56%. TTONL was nearly spherical in shape and uniform in size, and the average particle size was 227.8 ± 25.3 nm with negative charge. The specific disappearance of the TTO peak in the infrared spectrum suggested the successful preparation of TTONL, which showed high stability at 4°C within 35 d. The result of MIC test found that the nanoliposomes improved antibacterial activity of TTO against various E. coli strains. TTONL exposure in vitro caused different degrees of structural damage to the E. coli. TTONL by oral administration alleviated the clinical symptoms and intestinal lesion of chickens induced with E. coli challenge. Furthermore, TTONL treatment remarkably lowered the mRNA expression of NLRP3 and NF-κB (p65) in the duodenum and cecum of E. coli-infected chickens. In conclusion, the prepared TTONL had good stability and slow-release property with dose-dependent inhibition and killing effects on different strains of E. coli, and exerted a preventive role against chicken colibacillosis through inhibition.

Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy

Saudi Arabia has a rich culture of folk medicines and three such common herbs used by Saudi people for therapy of breast cancer are Turmeric (Kurkum) Curcuma longa, Chamomile (Babunaj) Matricaria chamomilla, and Aswaghantha (Aswaghadh) Withania somnifera. Hence, the present study aims to develop a polyherbal phytosome formulation by thin film hydration technique with a synergistic anti-cancer effect for the treatment of breast cancer. The phytosomes were standardized for their phytoconstituents by HPTLC and showed the best optimal properties with a mean vesicle diameter of less than 200 nm, zeta potential in the range of −24.43 to −35.70 mV, and relatively integrated structure with fairly uniform size on TEM. The in vitro MTT assay on MCF-7 breast cancer cell lines and MDA MB 231 breast adenocarcinoma cell lines was carried out. MTT assay on MCF-7 breast cancer cell lines indicated that plant extract-loaded phytosomes exhibited enhanced cytotoxic effects at IC50 values. of 55, 50, 45, 52, 42, 44, and 20 µg/mL compared to the extracts of C. longa, M. chamomilla, W. somnifera, and their combined extracts (80, 82, 74, 60, 70, 60, and 35 µg/mL respectively). Moreover, intracellular reactive oxygen species production was found to be higher for phytosomes treated cells at respective IC50 concentrations when compared to extracts. Overall, the developed polyherbal phytosomes were found to be effective and afford synergistic effects for breast cancer therapy.

Tunable Polymeric Mixed Micellar Nanoassemblies of Lutrol F127/Gelucire 44/14 for Oral Delivery of Praziquantel: A Promising Nanovector against Hymenolepis nana in Experimentally-Infected Rats.

Hymenolepiasis represents a parasitic infection of common prevalence in pediatrics with intimidating impacts, particularly amongst immunocompromised patients. The present work aimed to snowball the curative outcomes of the current mainstay of hymenolepiasis chemotherapy, praziquantel (PRZ), through assembly of polymeric mixed micelles (PMMs). Such innovative nano-cargo could consolidate PRZ hydrosolubility, extend its circulation time and eventually upraise its bioavailability, thus accomplishing a nanoparadigm for hymenolepiasis tackling at lower dose levels. For consummating this goal, PRZ-PMMs were tailored via thin-film hydration technique integrating a binary system of Lutrol F127 and Gelucire 44/14. Box-Behnken design was planned for optimizing the nanoformulation variables employing Design-Expert® software. Also, in Hymenolepis nana-infected rats, the pharmacodynamics of the optimal micellar formulation versus the analogous crude PRZ suspension were scrutinized on the 1st and 3rd days after administration of a single oral dose (12.5 or 25 mg/kg). Moreover, in vitro ovicidal activity of the monitored formulations was estimated utilizing Fuchsin vital stain. Furthermore, the in vivo pharmacokinetics were assessed in rats. The optimum PRZ-PMMs disclosed conciliation between thermodynamic and kinetic stability, high entrapment efficiency (86.29%), spherical nanosized morphology (15.18 nm), and controlled-release characteristics over 24 h (78.22%). 1H NMR studies verified PRZ assimilation within the micellar core. Additionally, the in vivo results highlighted a significant boosted efficacy of PRZ-PMMs manifested by fecal eggs output and worm burden reduction, which was clearly evident at the lesser PRZ dose, besides a reversed effect for the intestinal histological disruptions. At 50 µg/mL, PRZ-PMMs increased the percent of non-viable eggs to 100% versus 47% for crude PRZ, whilst shell destruction and loss of embryo were only clear with the applied nano-cargo. Moreover, superior bioavailability by 3.43-fold with elongated residence time was measured for PRZ-PMMs compared to PRZ suspension. Practically, our results unravel the potential of PRZ-PMMs as an oral promising tolerable lower dose nanoplatform for more competent PRZ mass chemotherapy.

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

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

Development and evaluation of ultradeformable vesicles loaded transdermal film of boswellic acid

BackgroundBoswellic acid (BA), a phytoconstituent obtained from Boswellia serrata, suffers from several limitations after oral administration such as poor systemic absorption, high first-pass metabolism and high frequency of dose requirement, which creates a need to develop an alternative route for drug administration via novel drug delivery formulation. The present research work aims at developing ultradeformable vesicular carriers (transferosomes) for transdermal delivery of boswellic acid to effectively deliver the drug into deeper layers of the skin reaching the target site and thus improving its systemic bioavailability. Ultradeformable vesicles were prepared by thin-film hydration technique, and the formulation was optimized using 32 full factorial design where the amount of lecithin (mg) and concentration of surfactant (%) were considered as independent variables. The formulated boswellic acid-loaded vesicles were incorporated into transdermal film via solvent evaporation technique using the blend of polymers such as starch and HPMC K4M.ResultsThe BA-loaded transferosomes were optimized based on vesicle size (nm) and drug entrapment efficiency (%EE), and the results were found to be 205.4 ± 1.215 nm and 86.39 ± 0.019%, respectively. Transmission electron microscopy (TEM) of optimized batch showed spherical shape of vesicles with identified lamellarity, surface charge of vesicles with high negative value − 15.2 mV that suggests electrostatic repulsion between vesicles, while the formulation showed good deformability index of 11.31 ± 0.032% due to use of Tween 80 as surfactant. In vitro permeation study demonstrated sustained release pattern of 96.53 ± 0.023% up to 24 h. Also, the in vitro drug diffusion study was carried out for transfersomal transdermal film which exhibited enhanced permeation and sustained retention of drug up to 94.71 ± 0.019% for 24 h.ConclusionAccordingly, the research work suggested that the transferosomes provided an efficient nanosized carriers for enhanced permeation of boswellic acid into deeper layers of skin and could successfully exhibit its therapeutic effect.

Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation

The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 31.22 multilevel categoric design with Design Expert® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from −23.8 ± 2.65 to −82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm2. The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema.

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives.

Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and −36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.

Formulation, in-vitro and ex-vivo evaluation of albendazole loaded ufasomal nanoformulation for topical delivery

Albendazole (ABZ), a widely used anti-parasitic agent, has recently drawn considerable attention due to its wide variety of therapeutic activities, such as anticancer and anti-psoriasis properties. However, its low water solubility limits its clinical applicability. The aim of the current study was to prepare ABZ loaded ufasomes (ABZ-U) to improve drug solubility and permeation through skin for topical delivery. ABZ-U was formulated by a thin film hydration and homogenization technique. Optimized ABZ-U was characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The formulation was further incorporated into a ufasomal gel base (ABZ-UG) and evaluated for drug release, rheology, and skin deposition. The optimized nanovesicles presented small particles size (235.71 ± 33.77 nm), good PDI (0.192 ± 0.088), acceptable zeta potential (−67.46 ± 2.35 mV) and entrapment efficiency of 74.14 ± 0.70%. The hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. Analyzing in vitro drug release study by various mathematical models, the optimized ABZ-UG showed a zero-order release pattern with 99.86 ± 0.79% cumulative ABZ release within 24 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of ABZ for topical delivery. Overall, the study proved that ABZ-UG could be a promising carrier in treatment of skin diseases.

Cationic Okra gum coated nanoliposomes as a pH-sensitive carrier for co-delivery of hesperetin and oxaliplatin in colorectal cancers

Oxaliplatin (OXP) is the typical treatment for colorectal cancer. Combining chemotherapeutic drugs can reduce drug resistance and side effects. In the present study, the co-delivery of OXP with Hesperetin (HSP), a natural anti-cancer flavonoid, by nanoliposomes was studied against HT-29 colon cancer cells. Cationic Okra gum (COG) was synthesized to coat nanoliposomes. The successful synthesis of COG was confirmed by NMR spectroscopy. Liposomes were prepared by thin film hydration technique. Formulations containing 0.5, 1, and 2 mg·ml−1 COG, had particle sizes ranging from 145 to 175 nm and zeta potentials for uncoated and coated formulations changed between −29 and −0.403 mV. Coated liposomes released 98 and 66% of HSP and OXP, respectively during 24 h pH-dependently. Cationic Okra gum enhanced the physical stability of the liposomes for about 30 days. The composite liposomes containing OXP and HSP at final concentrations of 1.125 and 125 µM, respectively could generate significant cytotoxicity at 48 h in comparison to each drug alone. Extracted drug-target interactions from the STITCH database, showed that Catalase (CAT) is the common target between OXP and HSP drugs. Measurement of the CAT activity may be used as an indicator to investigate the mechanism of action of these drugs in subsequent experiments.

Optimization of clobetasol propionate loaded niosomal gel for the treatment of psoriasis: Ex vivo and efficacy study

Psoriasis is a chronic autoimmune inflammatory skin disease treated using corticosteroids. The current topical therapy is very challenging owing to the physicochemical nature of corticosteroids and thick psoriatic stratum corneum. In this paper, clobetasol propionate-loaded niosomal gel was tailored to increase drug permeation and deposition (high local drug concentration) in the psoriatic area for effective management of psoriasis. Thin film hydration technique and sonication was used to formulate niosomal gel using Span 60, cholesterol 934 (as gelling agent). Size (188 nm) and entrapment efficacy (78%) of the niosomes were optimized using Box Behnken design (BBD) approach by selecting cholesterol = 261.6 mg, Span 60 = 1.49% and sonication time = 8.6 min. The optimized niosomal gel showed acceptable size (188 ± 6 nm), zeta potential (−38 ± 6 mV), and viscosity (8521 ± 121 cp) for topical application. The ex vivo permeation profile showed high permeability of niosomes (61.12 ± 1.89% in 24 h) compared to marketed clobetasol propionate cream USP (8.56 ± 2.5% in 24 h). Niosomal gel showed 5.1-fold improvement in drug deposition in stratum corneum and viable layers compared to marketed cream. Fluorescence study indicates high localization of vesicular system in the skin layers. Further, in imiquimod-induced psoriatic model, the PASI (psoriasis area severity index) was significantly decline (better efficacy) with gel compared to marketed cream. Thus, the data demonstrated the potential of niosomal gel to improve drug permeation and deposition in the affected skin for effective management of psoriasis.

Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: in-vitro, ex-vivo, and in-vivo evaluation

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X1), terpenes concentration (X2), terpenes type (X3), and chitosan concentration (X4) as independent variables, while their impact was observed for entrapment efficiency percent (Y1; EE%), particle size (Y2; PS), zeta potential (Y3; ZP), and amount of drug released after 6 h (Y4; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.