Concentration Of Poloxamer Research Articles

In vitro evaluation of poloxamer in situ forming gels for bedaquiline fumarate salt and pharmacokinetics following intramuscular injection in rats

The objective of this study was to evaluate in vitro and in vivo drug release from in situ forming gels prepared with poloxamer 338 (P338) and/or 407 (P407) in N-methyl-2-pyrrolidone (NMP)/water mixtures for the model compound bedaquiline fumarate salt. The impact of total poloxamer concentration (20%–25% (w/w)), P338/P407 ratio (100/0%–0/100% (w/w)) and NMP/water ratio (0/100%–25/75% (v/v)) on gel point temperature (GPT) was investigated via a design of experiments (DoE), showing that GPT decreased mainly with increasing poloxamer concentration and decreasing P338/P407 ratio, while the relation with NMP/water ratio was more complex resulting in a flexion. Based on the DoE, four formulations with 10 mg/g bedaquiline fumarate salt, a fixed NMP/water ratio of 25/75% (v/v) and varying total poloxamer concentration and P338/P407 ratio were selected for evaluation of gel erosion in vitro. The fastest eroding formulation had the lowest total poloxamer concentration (20% (w/w)) and the lowest P338/P407 ratio (20.4/79.6% (w/w)), while the formulation with the highest total poloxamer concentration (23.5% (w/w)) and highest P338/P407 ratio (100/0% (w/w)) showed the lowest gel erosion rate. These fast and slow eroding formulations showed a similar trend for in vitro drug release and in vivo pharmacokinetics after intramuscular (IM) injection in rats. In vivo tmax of the IM administered poloxamer in situ forming gels was about 6 h and a short-term sustained drug release was observed in vivo in rats up to 24 h after dosing, similar to a solution of bedaquiline fumarate salt in polyethylene glycol (PEG400)/water. In conclusion, IM administration of the evaluated poloxamer in situ forming gels may be useful for drugs that require a short-term sustained release, but is not able to extend drug release rates up to weeks or months.

Formulation and Evaluation of Cubosomes as Skin Retentive System for Topical Delivery of Clotrimazole

Objectives: Clotrimazole is a broad-spectrum antimycotic that widely used to treat fungal infections topically. However, poor water solubility of clotrimazole and low skin retention of its topical products present a hindrance for local availability and effectiveness of this drug. This study aimed to formulate and evaluate cubosomes as skin retentive system for topical delivery of clotrimazole. Methods: Six clotrimazole cubosomal dispersions (F1-F6) were prepared by emulsification of glyceryl monoloeate (GMO) and poloxamer 407 at different compositions in water with and without polyvinyl alcohol (PVA).The dispersions were examined under polarizing microscope and transmission electron microscope (TEM) for confirming cubosomes formation. The four cubosomal dispersions (F3- F6) that found to be successfully developed were evaluated in terms of pH, particle size, zeta potential, rheological behavior, entrapment efficiency and in vitro drug release. The formulae F3 (without PVA) and F6 (with PVA) comprising the highest concentration of poloxamer in the disperse phase (15%w/w) provided the highest clotrimazole cumulative percentage release and subjected to comparative ex vivo skin retention and permeation studies with marketed clotrimazole cream. Results: Both F3and F6 showed significantly lower clotrimazole permeation compared to the cream. Moreover, F6achieved the highest skin retention for clotrimazole. The F6 was compared with the cream for its irritation potential in rats and also for antifungal activity in rats inducted with candida albicans. The investigations showed that F6 was well tolerated as the cream. Also,F6 showed superior antifungal activity compared to the available marketed cream. Conclusions: The developed F6 cubosomes is a promising dosage form for safe and effective topical delivery of clotrimazole.

Systematically Optimized Imiquimod-Loaded Novel Hybrid Vesicles by Employing Design of Experiment (DoE) Approach with Improved Biocompatibility, Stability, and Dermatokinetic Profile.

The present research work explored the possibility of harnessing the benefits of vesicular carriers for overcoming imiquimod-associated complaints or side effects. Hybrid vesicles were prepared by the most common and easily scalable method, i.e., thin film hydration. The chaffing of myriad of factors, both process and material related, affecting the desirable attributes of conceived vesicles, was performed through Taguchi design. Based upon the analysis of Pareto chart and prior experiences, concentration of phospholipid and poloxamer 407 was selected for optimization by 2 levels, 13 run central composite design (CCD). The optimized hybrid vesicles contained 1% w/v phospholipid and 3% w/v poloxamer 407. The optimized hybrid vesicles were incorporated into the 3% w/v carbopol 940 gel and characterized for morphology, physicochemical properties, and rheological behavior. The release (%) and skin retention (% of total dose) across rat skin from gel at same amount of formulation was more than Imiquad®. The gel delivered the loaded cargo, preferably, in the viable region of skin and formed local depot in confocal microscopic studies. The gel followed one compartment open body dermatokinetic model in rat skin. There was not any harmful effect on the mice skin after repeated applications. The gel was stable at room conditions for 1year.

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

PLACKETT–BURMAN DESIGN AS A TOOL FOR SCREENING AND PROCESS OPTIMIZATION OF RIVASTIGMINE-LOADED LIPID NANOCARRIERS

Objective: Plackett–Burman experimental design is used to identify the most important factors early in the experimentation phase when complete knowledge about the system is usually unavailable. The objective of this study was to screen out the most important factors affecting the size and entrapment efficiency of rivastigmine hydrogen tartrate (RHT) nanostructured lipid carriers (NLCs).Methods: The RHT-loaded NLC was prepared by the modified solvent emulsification-diffusion method. The independent variables selected for Plackett–Burman design were drug: lipid ratio, solid lipid/liquid lipid (S/L) ratio, concentration Ryoto sugar ester (%w/v), the concentration of poloxamer 188 (%w/v), sonication time (min), sonication amplitude, and stirring time (h).Results: The R2 value for the particle size equation was 86.16%. p value was (<0.05) 0.048 in case of sonication time. In case of entrapment efficiency, the R2 value was 87.12%. The p value (p<0.05) for S/L ratio and the Ryoto sugar (% w/v) was 0.028 and 0.042, respectively.Conclusion: It can be concluded that sonication time has a significant effect on particle size, whereas S/L ratio and Ryoto sugar ester concentration have a significant effect on entrapment efficiency.

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

Effect on Nail Structure and Transungual Permeability of the Ethanol and Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer.

Aqueous-based nail lacquers have shown potential in promoting the diffusion of drugs into the nail. In our laboratory, we have recently developed a transungual delivery system based on an aqueous dispersion of cyclodextrin-poloxamer soluble polypseudorotaxanes, supramolecular host−guest assemblies that improves the drug permeation into the nail. However, the high-water content and the rheological and adhesive properties of this lacquer negatively affect properties that play a fundamental role in the patients’ acceptance such as stickiness, nail film formation or drying rate, properties. In this work, we have optimized the composition of these lacquers to improve these properties whilst maintaining good drug permeation profiles. Incorporating ethanol into the vehicle and reducing the proportion of Poloxamer 407 (PL), provided a good strategy. The use of hydro-ethanolic mixtures (>50% ethanol) and the reduction of the poloxamer concentration significantly improved the lacquer drying speed by reducing the stickiness and promoting film formation on the nail surface. Additionally, in a surprising way, the use of hydro-ethanolic vehicles further enhanced the permeation of ciclopirox olamine and clobetasol propionate, used for the treatment of onychomycosis and nail psoriasis respectively, into the nail and hooves.

Thermosensitive in-situ forming gels for ophthalmic delivery of tea polyphenols

This study aimed to develop a thermosensitive in situ gelling vehicle containing tea polyphenols (TPs) for ophthalmic delivery. Based on the different experiments of appropriate gel strength and gelling capacity under physiological conditions, the optimized concentrations of poloxamer 407/poloxamer 188 and carbopol 940 in the formulation were established to be 25% (w/v)/5% (w/v) and 0.1% (w/v), respectively. The combined solutions could be easily dropped as a fluid into the eye and further converted to gels under physiological conditions. Furthermore, using rabbit cornea, the effects of various formulation factors on the permeation of TPs were investigated both in vitro and in vivo. According to the outcome of transcorneal penetration experiment through the excised rabbit cornea in vitro, the formulation of F4 including 0.1% Azone showed the highest apparent permeability coefficient (Papp). Meanwhile, the result of ocular pharmacokinetic studies showed the area under the curve of the aqueous humor concentration-time profiles of TPs gel including 0.1% Azone was 2.83 times higher than that of TPs solution in the presence of Azone. These results demonstrate the in situ gel-forming delivery system may hold some promise in ocular delivery and can be a viable alternative to enhance the ocular bioavailability.

Topical Delivery of Erythromycin Through Cubosomes for Acne.

Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne.

Novel in-situ gel for intravesical administration of ketorolac

The urinary bladder stores urine until the time of urination. Systemic administration of drugs to treat bladder diseases faces several limitations. Therefore, intravesical drug delivery is a promising alternative route of administration. An in-situ gel is used to form a gel inside the bladder cavity and ensure continuous release of the drug even after urination. The objective of the present study was to optimize an in-situ gel formulation of poloxamer and chitosan for intravesical delivery of ketorolac tromethamine. The gelling temperature of the prepared combinations ranged from 20.67 to 25.8 °C. In-vitro release of KT was sustained for up to 7 h using a poloxamer concentration ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%. Design-Expert® 10 was used to select the optimized formulation (poloxamer/chitosan 17/1.589% w/w) which significantly (p < 0.05) extended the drug release more than each polymer alone. An ex-vivo study showed the ability of the optimized formulation to sustain drug release after emptying two times to mimic urination. Furthermore, the formed gel adhered to the bladder tissue throughout the time period of the experiment. Intravesical administration of the optimized formulation to rabbits via catheter showed no obstruction of urine flow and continuous release of the drug for 12 h.

Investigation of Methylene Blue Release from Functional Polymeric Systems Using Dielectric Analysis.

Methylene blue (MB) is a photosensitizer used in photodynamic therapy (PDT) to treat colorectal cancer tumors and leishmaniasis infection. The clinical efficacy of PDT using MB is dependent on the physicochemical characteristics of the formulation. Bioadhesive thermoresponsive systems containing poloxamer 407 and Carbopol 934P have been proposed as platforms for PDT. However, the effect of MB on the physicochemical properties of these platforms is not fully understood, particularly in light of the MB availability. The aim of this study was to investigate the dielectric characteristics of functional polymeric systems containing MB and their influence on mucoadhesion and drug release. Binary polymeric systems containing different concentrations of poloxamer 407, Carbopol 934P and MB were evaluated as dielectric and mucoadhesive properties, as well as in vitro drug release profile. MB, temperature and polymeric composition influenced the physicochemical properties of the systems. The presence of MB altered the supramolecular structure of the preparations. The mucoadhesive properties of systems were influenced by MB presence and the formulation with the lowest amount of MB displayed faster release. The lower MB concentration in the systems displayed better results in terms of ionic mobility and drug release, and is indicative of a suitable clinical performance.

Development of poloxamer gel formulations via hot-melt extrusion technology

Poloxamer gels are conventionally prepared by the “hot” or the “cold” process. But these techniques have some disadvantages such as high energy consumption, requires expensive equipment and often have scale up issues. Therefore, the objective of this work was to develop poloxamer gels by hot-melt extrusion technology. The model drug selected was ketoprofen. The formulations developed were 30% and 40% poloxamer gels. Of these formulations, the 30% poloxamer gels were selected as ideal gels. DSC and XRD studies showed an amorphous nature of the drug after extrusion. It was observed from the permeation studies that with increasing poloxamer concentration, a decrease in drug permeation was obtained. Other studies conducted for the formulations included in-vitro release studies, texture analysis, rheological studies and pH measurements. In conclusion, the hot-melt extrusion technology could be successfully employed to develop poloxamer gels by overcoming the drawbacks associated with the conventional techniques.

Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release

Houttuynia cordata (H. cordata) has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs) were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin) were 92.9–95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

On the Production of Chitosan-Coated Polycaprolactone Nanoparticles in a Confined Impinging Jet Reactor

This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL−1) and of chitosan (in the range 1.5-5 mg mL−1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min−1 is required in the considered reactor to minimize the particle size.

Preparation and Evaluation of Chloramphenicol as Thermosensitive Ocular in- situ Gel

The purpose of this study was to develop poloxamer-based in-situ gel of chloramphenicol aiming to increase bioavailability and prolong corneal contact time, controlling drug release, and enhancing ocular bioavailability. The in-situ gel was prepared using different concentrations of poloxamer 407 combined with hydroxypropyl methyl cellulose (HPMC) or carbapol 940 to achieve gelation temperature about physiological temperature and improve rheological behavior and gelling properties of poloxamer gel. The prepared formulations were evaluated for their appearance, pH, and sol-gel transition temperature. The formulations F2, F3, and F5 have a gelation temperature within the accepted range 35-370C and were evaluated for their isotonicity, rheological studies, ocular irritation test, sterility and release studies. The selected formulations (F2,F3, and F5) isotonic, pseudoplastic, non irritant, pass sterility test, and the in vitro release demonstrated a diffusion-erosion controlled release of chloramphenicol over a period of 4 hr., 6 hr., and 6 hr. respectively.&#x0D; Key words: Chloramphenicol, in-situ gel, ocular dosage form, poloxamer.

Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening.

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.

Thermoreversible in situ gel for subgingival delivery of simvastatin for treatment of periodontal disease.

Objective:The aim of this in vitro study was to formulate an in situ thermoreversible injectable gel with poloxamer (PM) and methylcellulose (MC) to deliver simvastatin (SMV) in a controlled manner.Subjects and Methods:Preformulation studies (Fourier transform infrared and differential scanning calorimetry) to assess the interaction between SMV and MC and PM were performed before gel formulation. Keeping the concentration of SMV at 2.2%, the concentration of PM and MC was altered to formulate in situ thermosensitive gel at 37°C. Rheological studies were carried to analyze the physical property of the various formulations. Drug release profile and stability studies were done for the selected formulation. The in vitro drug release profile was carried out for using open end tube method and ultraviolet spectroscopy.Results:The preformulation studies showed that there is no interaction between the polymer and drug based on the rheological studies of different formulation, the formulation. F8 gels at 37°C and attains a viscosity of 4150 cps.Conclusions:PM 25% and MC 5% formed an ideal thermosensitive injectable gel at 37°C for subgingival delivery of SMV and also show controlled drug release for the period of 10 days in vitro.

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

In this study, transdermal etodolac-loaded cubosomes were developed in order to relieve patient pain and joints stiffness by providing stable etodolac concentration at the targeting sites through controlled drug delivery via the noninvasive skin route with more sustaining and less frequent dosing. Different ratios and percentages of poloxamer 407 and monoolein were used to formulate the cubosomes using emulsification and homogenization processes. The etodolac-loaded cubosomes showed particle size values ranging from 135.95 to 288.35 nm and zeta potential values ranging from −18.40 to −36.10 mV. All the cubosomes offered an encapsulation efficiency value of about 100% and showed drug loading capacity ranging from 1.28 to 6.09%. The in vitro drug release studies revealed a controlled drug release profile with a drug release rate up to 15.08%/h. Increasing poloxamer concentration in etodolac-loaded cubosomes resulted in nanoparticles with less particle size and faster drug release. The particles exhibited cubic and hexagonal shapes. The DSC and X-ray analysis demonstrated that the drug was encapsulated in the cubosomes bicontinuous structures in amorphous form. In addition, investigated cubosomes exhibited fast drug penetration through excited mice skin followed by slower drug penetration for up to 24 h. The pharmacokinetic study in human volunteers showed that the selected etodolac-loaded cubosomes enhanced the bioavailability of etodolac as compared to the oral capsules (266.11%) with evidence of longer half-life and higher MRT that reached 18.86 and 29.55 h, respectively. The etodolac-loaded cubosomes propose a promising system for treatment of arthritis simply through skin application.

Characterization of Lipid-Based Hexosomes as Versatile Vaccine Carriers

Subunit vaccines typically show insufficient immunogenicity. To address this issue, we developed a novel self-adjuvanting particulate carrier system based upon the lipids phytantriol (Phy) and mannide monooleate (MaMo). Phy is a lipid known to form nonlamellar phases in fully hydrated systems, whereas MaMo has been found to promote immune responses in emulsion form. A bulk phase composition of Phy/MaMo (14 wt %) showed hexagonal (HII) phase behavior over a practical temperature range (including room and body temperature), and was therefore used for particle development. Hexosomes stabilized with different concentrations of either poloxamer 407, Myrj 59, or Pluronic F108 were successfully prepared. To demonstrate the versatile nature of these systems, the particles were further modified with either positively or negatively charged lipids and loaded with model antigens, while maintaining the HII structure. These hexosomes are structurally robust and amenable to customization, rendering them suitable as antigen delivery carriers.