Surfactant Poloxamer Research Articles

Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes

BackgroundPolymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration.ResultsChitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8–56.2 mV values, while the dialyzed samples led to smaller particle sizes (152–184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process.ConclusionsIn Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis.

Dexamethasone acetate nanocrystals: characterization and dissolution studies in presence of polymorphic phases.

A drug with poor water-solubility, like Dexamethasone acetate, can present lower bioavailability conventional for pharmaceutical formulations, and the presence of polymorphs in the raw material can lead to drug quality problems. In this study, nanocrystals of dexamethasone acetate were synthesized by high pressure homogenizer (HPH) method in surfactant poloxamer 188 (P188) solid dispersion and the bioavailable in raw material with polymorphism presence was evaluated. The powder pre-suspension was prepared by the HPH process, and the nanoparticles formed were incorporated in P188 solutions. The nanocrystals formed were characterized by techniques of XRD, SEM, FTIR, thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), dynamic light scattering (DLS) to analyze the particle size and zeta potential, and in vitro evaluation by dissolution studies. The characterization techniques were adequate to show the presence of raw material with physical moisture between two dexamethasone acetate polymorphs. The nanocrystals formed in the presence of the P188 in the formulation showed a considerable increase in the rate of dissolution of the drug in the medium and in the size of the stable nanocrystals, even in the presence of dexamethasone acetate polymorphs. The results showed that it was possible to produce dexamethasone nanocrystals by HPH process with regular size by the presence of the small amount of P188 surfactant. This article presents a novelty in the development of dexamethasone nanoparticles that have different polymorphic forms in their physical composition.

Nanostructured lipid carriers mediated transdermal delivery of trandolapril as an impeccable therapeutic approach against hypertension: Development, characterization and in vivo evaluation

The study aimed to design trandolapril-embedded nanostructured lipid carriers (NLCs) transdermal patch and evaluate its in vitro drug permeation, bioavailability and pharmacokinetics. Trandolapril, a poorly soluble drug with antihypertensive activity, was used and investigated in the development of NLCs formulations. High-pressure homogenization was used to develop the drug-loaded NLCs formulations, which were then optimized utilizing the box Behnken design. The optimized batch of NLCs formulation includes oleic acid as liquid lipid, solid lipid as Precirol ATO 5 and surfactant poloxamer 188. The developed NLCs had a mean particle size of 82.48 ± 2.16 nm and a zeta potential of – 20.6 ± 2.18 mV. Tailored NLCs were loaded into the transdermal patch and molded using a solvent casting technique and evaluated for thickness, moisture content, weight variation and folding endurance. Furthermore, the in vitro permeation of trandolapril from the transdermal patch was measured using Franz diffusion cells and compared to a pure trandolapril patch. When compared to an oral trandolapril suspension, in vivo pharmacokinetic studies with an NLCs-loaded transdermal patch reveal an increase in maximum plasma concentration (Cmax) and concentration-time curve (AUC). These findings showed that trandolapril-NLCs might be a viable transdermal delivery option.

Concentration-Dependent Viscoelasticity of Poloxamer-Shelled Microbubbles.

The oscillation of shelled microbubbles during exposure to ultrasound is influenced by the mechanical properties of the shell components. The oscillation behavior of bubbles coated with various phospholipids and other amphiphiles has been studied. However, there have been few investigations of how the adsorption conditions of the shell molecules relate to the viscoelastic properties of the shell and influence the oscillation behavior of the bubbles. In the present study, we investigated the oscillation characteristics of microbubbles coated with a poloxamer surfactant, that is, Pluronic F-68, at several concentrations after the adsorption kinetics of the surfactant at the gas-water interface had reached equilibrium. The dilatational viscoelasticity of the shell during exposure to ultrasound was analyzed in the frequency domain from the attenuation characteristics of the acoustic pulses propagated in the bubble suspension. At Pluronic F-68 concentrations lower than 2.0 × 10-2 mol L-1, the attenuation characteristics typically exhibited a sharp peak. At concentrations higher than 2.0 × 10-2 mol L-1, the peak flattened. The dilatational elasticity and viscosity of the shell were estimated by fitting the theoretical model to the experimental values, which revealed that both the elasticity and viscosity increased markedly at approximately 2.0 × 10-2 mol L-1. This suggests that the adsorption properties of Pluronic F-68 strongly affect the oscillation characteristics of microbubbles of a size suitable for medical ultrasound diagnostics.

Toward an Electronic Tongue Based on Surfactant-Stabilized Chemosensory Microparticles with a Dual Detection Mode.

We propose a novel type of electronic tongue based on four types of monodispersed chemosensory microparticles (MPs) with a lipophilic core stabilized by a nonionic poloxamer surfactant. The lipophilic core composition was designed to achieve cross-sensitivity toward various ions and to enable spectrophotometric and/or spectrofluorimetric detection. Thus, generic anion-selective MPs, generic cation-selective MPs, as well as two types of metalloporphyrin-based MPs were fabricated and their morphology was characterized. Next, their differential sensing ability toward the discrimination of five l-tyrosine derivatives (dopamine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxy-l-phenylalanine, normetanephrine, 4-hydroxy-3-methoxymandelic acid) was assessed. Comparison with the respective ion-selective electrode (ISE) responses was also provided to verify if the results from the potentiometric e-tongue correspond to outputs of the developed MP optode array. The recognition of dietary supplements containing l-tyrosine (l-Tyr) derivatives with the use of the MP-based e-tongue proved the potential of the developed sensing assay in pharmaceutical analysis.

Formulation and evaluation of a novel cubosomal emulgel for topical delivery of luliconazole

Abstract Despite numerous remarkable developments in clinical therapy, the world remains firmly in the grip of fungal infections. While conventional approaches to antifungal therapy are failing, dermatophytes continue to affect people’s daily lives, especially in humid and tropical areas, and pose a major medical problem. Cubosomes, the liquid crystalline nanostructures, are among the recently developed lipid nanoparticles that could potentially overcome the hurdles of conventional therapy. In the present study, cubosomes containing luliconazole, an antifungal drug, were formulated to overcome the limitation of poor water solubility and poor bioavailability of the drug for the main purpose of treating fungal infections. Various formulations of luliconazole loaded cubosomes were prepared with different ratios of lipid (glyceryl monooleate) and surfactant (poloxamer 407) using emulsification method. The prepared formulations were optimised and the optimised cubosomal dispersion was loaded into a carbomer-934 gel to form an emulsifying gel. All cubosomal dispersions had particle sizes ranging from 124 nm to 221.1 nm, optimal zeta potential and polydispersity index, and were found to be stable. The drug entrapment efficiency of the cubosomes was over 90%. The in vitro diffusion study showed that the developed formulation had a higher release rate than the marketed formulation. The in vitro antifungal activity study confirmed that the prepared emulsion formulation was also effective against Candida albicans. The novel drug delivery system developed in this study, the cubosomal emulgel, could thus be a favourable approach for the topical delivery of luliconazole for the treatment of fungal infections.

Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity.

Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ −9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol’s release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.

Design expert assisted formulation, characterization and optimization of microemulsion based solid lipid nanoparticles of repaglinide.

Repaglinide, a member of the meglitinide class of drugs, is a new anti-diabetic agent that is utilized as an oral hypoglycemic agent. Using glyceryl monostearate, cetyl palmitate, and tristearin as lipids and poloxamer 188 as a surfactant, repaglinide-loaded solid lipid nanoparticles were created. Solid lipid nanoparticles were prepared utilizing an o/w microemulsion technique, which included the lipids glyceryl monostearate and tristearin, as well as waxes such as cetyl palmitate and the surfactant poloxamer 188. The mean particle size of the solid lipid nanoparticles formed was around 339nm, with an entrapment efficiency of 82.20%. In-vitro release studies continued to be conducted using the dialysis bag diffusion technique. Within 12h, the cumulative drug release was 88.4%. The results indicate that repaglinide was released more slowly from solid lipid nanoparticles made from tristearin and glyceryl monostearate in an equal ratio. Tristearin found the controlled release and extreme entrapment from other lipid carriers like glyceryl monostearate and cetyl palmitate. Differential scanning calorimetry demonstrates that repaglinide is entangled in amorphous or molecular state within solid lipid nanoparticles. SEM microscopy revealed that the produced repaglinide solid lipid nanoparticles had a spherical shape. After one month of storage at 2-8°C, short-term stability testing revealed no significant alteration.

Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections.

Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer–Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome® for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.

Development and evaluation of colon targeted delivery of budesonide polymeric nanoparticles for colitis therapy

Targeted delivery of the drug at site of action in case of Inflammatory Bowel Disease like colitis is the big challenge for formulators. The case where conventional drug delivery fails in severe stages of Inflammatory Bowel Disease, Nanoparticles is good dosage form to targeted inflammatory site. The idea of the this research was to prepare Nanoparticles with polymer Eudragit S100 and Surfactant Poloxamer containing Budesonide which finally filled in capsules providing immediate release at the ileocecal site, the most affected area in IBD i.e. pH dependent release. Nanoparticles are prepared by nanoprecipatation technique. Budesonide was used as a drug because of its therapeutic potential for in IBD. This study compares the different ratios of drug to polymer and drug to surfactant with optimized solvent and antisolvent concentration in preparation of Nanoparticles. Optimized formulation ratio of drug to polymer was 1:2 and drug to surfactant was 1:1. The optimized batch of nanoparticles was filled in capsule and was evaluated for in-vitro studies.

α-Lipoic acid nanocapsules fortified cow milk application as a dietary supplement product for anemia

Anemia is an iron deficiency disease caused by the lack of red blood cells to carry sufficient oxygen to the body tissues. Lipoic acid is naturally occurring organosulfur compound with antioxidant property had chosen for the present work to maintain the red blood cell counts through its redox mechanism. The current study aimed to develop lipoic acid nanocapsules (LANCPs) fortified A2 cow milk, thereby this product may act as a natural nutritional supplement. Based on the concept of oil-lipid core with polymeric shell to improve the solubility of the hydrophobic drug. The polymeric surfactant poloxamer 188 increase the LA solubility, coconut oil act as a natural stabilizer and the emulsifier egg lecithin enhanced the stability of the formulation. By varying the concentrations of lipoic acid and poloxamer 188 different trials were performed. The results of FT-IR analysis exhibited the compatibility nature of LA, poloxamer 188, coconut oil, and egg lecithin. The morphology of the developed formulation was observed to be spherically arranged core shell with size ranging from 243.7 ± 9.46 to 394.6 ± 4.05 nm with a surface charge of − 8.04 ± 0.48 to − 1.8 ± 0.5 mV. Results of DPPH assay indicate that the antioxidant property of LANCPs-FM gets maintained even after fortification compared to LANCPs. RP-HPLC analysis showed the presence of LA in LANCPs-FM. In-vitro release of LA from LANCPs-FM showed that 96.28 ± 2.35% of LA were sustained release from LANCPs-FM at 4 h. The results of in-vivo studies in anemia induced rats showed that the blood counts (RBC and Hb) of LANCPs-FM supplemented rats gets increased compared to CM/LA-CM. This suggests that the developed LANCPs might be effective for the treatment of anemia progression especially for patients undergoing hemodialysis.

A dense graphene monolith with poloxamer prefunctionalization enabling aqueous redispersion to obtain solubilized graphene sheets

The realization of good aqueous dispersibility of commercial graphene products composed of exfoliated graphene sheets is of significance for downstream applications. However, the tap density of commercial graphene powder is quite low (0.03–0.1 kg/m3), meaning that 1 kg graphene powder occupies about 10–30 m3 in volume during transportation. And, the available content of commercial graphene dispersion/slurry in aqueous medium cannot exceed 5 wt%, although the density is high (≈ 1050 kg/m3). In this work, a graphene monolith was prepared by oven-drying of graphene sheets prefunctionalized with poloxamer surfactants. Our graphene monoliths not only have a high density (1500 kg/m3) and high graphene content (≈ 10 wt%), but also a full capability to be completely redispersed (≈ 100%) in water by bath sonication to obtain solubilized graphene sheets, whose lateral size and thickness are unchanged compared to as-exfoliated ones. Moreover, a simple empirical method was proposed to predict the redispersion capability of graphene monoliths using different poloxamers by contact angle measurements. Our results provide a universal approach to make exfoliated graphene-based products with better downstream availability and lower transportation cost.

Using pyrene to probe the effects of poloxamer stabilisers on internal lipid microenvironments in solid lipid nanoparticles.

Solid lipid nanoparticles (SLNs) have proved to be effective nanocarriers with many advantages over other non-lipid-based systems. The development of new SLN formulations is often hindered through poor drug loading capacity and time-consuming optimisation of lipid/stabiliser combinations. One challenge in the development of new SLN formulations is understanding the complex interactions between amphiphilic stabilisers and hydrophobic lipids; the nature of these interactions can significantly impact SLN properties, including the internal polarity within the nanoparticle core. Herein, we report the use of pyrene to probe the internal lipid microenvironment inside SLNs. We investigate the effect of using different poloxamer stabilisers on the internal polarity of SLNs formed using the common solid lipid, Compritol 888 ATO. We show that the polarity of the internal lipid environment is modified by the length of the poly(propylene oxide) (PPO) block of the poloxamer stabiliser, with longer PPO blocks producing SLNs with less polar lipid cores. Blending of stabilisers could also be used to tune the polarity of the core lipid environment, which may allow for adjusting the polarity of the lipid to assist the loading of different therapeutics.

Synthesis of a long acting nanoformulated emtricitabine ProTide

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities and access stigma and fatigue are treatment limitations. These have led to new opportunities for the development of long acting (LA) ART including implantable devices and chemical drug modifications. Herein, medicinal and formulation chemistry were used to develop LA prodrug nanoformulations of emtricitabine (FTC). A potent lipophilic FTC phosphoramidate prodrug (M2FTC) was synthesized then encapsulated into a poloxamer surfactant (NM2FTC). These modifications extended the biology, apparent drug half-life and antiretroviral activities of the formulations. NM2FTC demonstrated a >30-fold increase in macrophage and CD4+ T cell drug uptake with efficient conversion to triphosphates (FTC-TP). Intracellular FTC-TP protected macrophages against an HIV-1 challenge for 30 days. A single intramuscular injection of NM2FTC, at 45 mg/kg native drug equivalents, into Sprague Dawley rats resulted in sustained prodrug levels in blood, liver, spleen and lymph nodes and FTC-TP in lymph node and spleen cells at one month. In contrast, native FTC-TPs was present for one day. These results are an advance in the transformation of FTC into a LA agent.

Vibration Characteristics and Persistence of Poloxamer- or Phospholipid-Coated Single Microbubbles under Ultrasound Irradiation.

Microbubbles shelled with soft materials are expected to find applications as ultrasound-sensitive drug delivery systems, including through sonoporation. Microbubbles with specific vibrational characteristics and long intravascular persistence are required for clinical uses. To achieve this aim, the kinetics of the microbubble shell components at the gas/liquid interface while being subjected to ultrasound need to be better understood. This paper investigates the vibration characteristics and lifetime of single microbubbles coated with a poloxamer surfactant, Pluronic F-68, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) under ultrasound irradiation. Air- and perfluorohexane (PFH)-filled microbubbles coated with Pluronic F-68 and DMPC at several concentrations (0 to 10-2 mol L-1) were produced. An optical measurement system using a laser Doppler vibrometer and microscope was used to observe the radial vibration mode of single microbubbles. The vibrational displacement amplitude and resonance radius of Pluronic- or DMPC-coated microbubbles were found to depend very little on the concentrations. The resonance radius was around 65 μm at 38.8 kHz under all the experimental conditions investigated. The lifetime of the microbubbles was investigated simultaneously by measuring their temporal change in volume, and it was increased with Pluronic concentration. Remarkably, the oscillation amplitude of the bubble has an effect on the bubble lifetime. In other words, larger oscillation under the resonance condition accelerates the diffusion of the inner gas.

&lt;p&gt;Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation&lt;/p&gt;

PurposeA palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug’s half-life, antiretroviral activities and biodistribution.MethodsA modified FTC prodrug (MFTC) was synthesized by palmitoyl chloride esterification. MFTC’s chemical structure was evaluated by nuclear magnetic resonance. The created hydrophobic prodrug nanocrystals were encased into a poloxamer surfactant and the pharmacokinetics (PK), biodistribution and antiretroviral activities of the nanoformulation (NMFTC) were assessed. The conversion of MFTC to FTC triphosphates was evaluated.ResultsMFTC coated with poloxamer formed stable nanocrystals (NMFTC). NMFTC demonstrated an average particle size, polydispersity index and zeta potential of 350 nm, 0.24 and −20 mV, respectively. Drug encapsulation efficiency was 90%. NMFTC was readily taken up by human monocyte-derived macrophages yielding readily detected intracellular FTC triphosphates and an extended PK profile.ConclusionNMFTC shows improved antiretroviral activities over native FTC. This is coordinate with its extended apparent half-life. The work represents an incremental advance in the development of a long-acting FTC formulation.

Development of methotrexate-loaded cubosomes with improved skin permeation for the topical treatment of rheumatoid arthritis

Methotrexate-loaded cubosomes (MTCs) were developed to provide relief from pain/joint stiffness, by affording stable methotrexate concentration at the targeting sites through sustained pattern by non-invasive skin route with enhanced permeation upon skin, for the treatment of rheumatoid arthritis. Non-ionic surfactant poloxamer 188 works to enhance the permeation of methotrexate. The results of FT-IR analysis indicates the compatibility nature of methotrexate (MT), poloxamer 188 and cetyl palmitate selected for the formulation. Different ratios of poloxamer 188 and cetyl palmitate were utilized to formulate using emulsification process. The selected MTCs showed particle size of around 626.13 ± 14.15 nm with charge of around − 6.29 ± 1.07 mV with cubic morphology. The encapsulation efficiency of MTCs was found to be 92.94 ± 0.9%. The in vitro MT release from MTCs conducted for 12 h revealed a sustained release pattern. The non-crystalline nature of MTCs was confirmed by XRD analysis. The in vitro anti-inflammatory effect of MTCs showed enhanced anti-inflammatory effect 11.9% compared to diclofenac sodium 10.4%. Ex vivo skin permeation analysis in excised skin of wistar albino rats showed 2.50 ± 0.3 ng of MT permeation within 2 h followed by 8.80 ± 5.2 ng within 12 h without any skin irritation. In addition, histopathological evaluation supported with fluorescent microscopic analysis of FITC-labeled MTCs confirmed the superior permeation enhancement of MTCs. The thermal stimulus time (TST) as studied by rat tail flick method indicates the enhancement of TST in case of MTCs (5.63 ± 0.21 s) compared to standard diclofenac gel (2.70 ± 0.20 s)/blank formulation (2.45 ± 0.23 s), which indicates the superior analgesic effect of the developed MTCs. The inflammed paw thicknesses were measured for CFA-induced arthritic rats which get reduced from day 1 (1.47 cm) to (1.03 cm) day 15 for MTCs-treated groups that were imaged by animal imaging system. Thus, the MTCs may act as a promising system for the treatment of RA upon topical application.

Nanostructured cubosomes in an in situ nasal gel system: an alternative approach for the controlled delivery of donepezil HCl to brain

The purpose of this research was to develop cubosomal mucoadhesive in situ nasal gel to enhance the donepezil HCl delivery to the brain. Glycerol mono-oleate (GMO) and surfactant poloxamer 407 were used to prepare cubosomes. The developed formulations were characterized for particle size (PS), poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), in vitro drug release and in vivo bio-distribution study in blood and brain tissue. Central composite design was used for the optimization purpose and the selected formulation (containing GMO 2 g and poloxamer 1.5%) was prepared in presence of gellan gum and konjac gum as gelling agent and mucoadhesive agent respectively. The optimal cubosomal dispersion and optimal cubosomal mucoadhesive in situ nasal gel were subjected to in vivo bio-distribution studies in rat model. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the drug solution. Thus, the formulated cubosomal mucoadhesive in situ gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.

Development of Curcumin-Loaded Solid Lipid Nanoparticles Utilizing Glyceryl Monostearate as Single Lipid Using QbD Approach: Characterization and Evaluation of Anticancer Activity Against Human Breast Cancer Cell Line.

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in the presence of surfactant Poloxamer 188 and evaluated the efficiency of SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had a particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 µg/mL after 24 h treatment. Furthermore, the treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide a strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy.