Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine.

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Novel approaches to cancer therapy with ibuprofen-loaded Eudragit® RS 100 and/or octadecylamine-modified PLGA nanoparticles by assessment of their effects on apoptosis.

Objective: The purpose of this study was the design ibuprofen (IBU)-loaded unique Eudragit® RS 100 (ERS) and/or octadecylamine modified PLGA nanoparticles (NPs) for cancer treatment.Significance: The rational for this approach is to bring a new approach to cancer treatment with modification of IBU-loaded PLGA NPs with ERS and/or octadecylamine by means of smaller particle size (PS), cationic surface, biocompatible nature, and investigating their selective efficacy on lung cell lines (A549 lung cancer cell and CCD-19Lu normal cell line).Methods: IBU encapsulated PLGA-based NPs were prepared and characterized for physical and solid-state analyses. In vitro release, MTT, and determination of apoptotic pathways were performed.Results: Considering characterizations, B, C, E, F, H, and K formulations with higher EE%, smaller PS and encouraging higher zeta potential were chosen for further experiments were intended to enhance anticancer action and apoptotic behavior. Formulations were showed biphasic release profile with extended release manner (Korsmeyer-Peppas model with a diffusion-controlled mechanism). The NPs effect on lung cancer cells with high specificity and affinity was demonstrated by MTT study. It was found that the effect of IBU was increased 4-28 times over the pure form. Annexin V-FITC/PI staining method, FITC Active Caspase-3 staining method, and mitochondrial membrane potential detection analyses was performed to determine the apoptotic pathways by flow cytometry.Conclusion: E coded NP is selected as a promising candidate with its highly specific affinity for human lung adenocarcinoma cells and could induce cell death effectively and be a potent system to treat lung cancer.

Design, characterization, and evaluation of aceclofenac-loaded Eudragit RS 100 nanoparticulate system for ocular delivery.

The aim of the present study was to develop and evaluate positively charged nanoparticles of aceclofenac for ocular delivery. The nanoparticles were prepared by the nanoprecipitation method using Eudragit RS 100. The optimized nanoparticles were found to have narrow particle size range (238.9 ± 8 nm) with nearly spherical shape, positive zeta potential (40.3 ± 3.8). Higher entrapment efficiency of aceclofenac (94.53 ± 1.0%) with prolonged in vitro drug release profiles was also observed. Powder X-ray diffraction and differential scanning calorimetry studies indicated decrease in crystallinity of drug within the nanoparticulate polymeric matrix. The formulation was found to have higher permeation as compared to aceclofenac aqueous solution. Nanoparticle formulation was found to be quite stable and well tolerated with no signs of corneal damage. The in vivo studies involving the arachidonic acid-induced ocular inflammation in rabbits showed optimal efficacy of the nanoparticles with significantly higher inhibition of polymorphonuclear leukocytes migration (p < 0.05) and lid closure scores.

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

Evaluation of the effect of some additives on the efficiency of binder liquid in wet agglomeration of crystals.

OBJECTIVE: Wet agglomeration is a process wherein dispersed particles are held together in an aggregated form by the presence of a small quantity of solvent which acts as binder liquid. In this work, the efficiency of binder liquid was tested in the presence of various additives. METHODS: Solid state of carbamazepine (CBZ) agglomerates was characterized by DSC and FT-IR. The obtained agglomerates were also investigated in terms of yield, size distribution, friability, and drug release. RESULTS: CBZ agglomerates formed only in the presence of talc, span, and croscarmellose sodium (CCS), whereas ethyl cellulose and eudragit RS100 failed to make CBZ agglomerates. The presence of talc decreased the agglomerate size and produced CBZ agglomerates with a poor strength. However, span and CCS led to larger agglomerates with superior strength. In contrast to CCS samples, span and talc altered the dissolution rate of CBZ. FT-IR results showed that there is an interaction between CCS and drug. CONCLUSION: This study suggests that care must be taken when additives are used to manufacture agglomerates as the type of additives even in low concentrations can have a big impact on the efficiency of the binder liquid in forming agglomerates thereby affecting the quality of agglomerates.

Development of Eudragit RS 100 Microparticles Loaded with Ropinirole: Optimization and In Vitro Evaluation Studies.

The current study aimed to develop novel pH independent microparticles loaded with ropinirole (ROP) for sustained drug release. Eudragit RS 100 was used as release retardant and microparticles were fabricated by oil-in-oil emulsion solvent evaporation method. A three-factor three-level Box-Behnken design using Design-Expert software was employed to optimize formulation variables. Ropinirole loaded microparticles were evaluated with respect to morphology, particle size, encapsulation efficiency, and in vitro release profile. Optical microscopy and SEM micrographs indicated spherical shape with smooth surface and well-defined boundary. The particle size was in the range of 98.86 to 236.29 µm, being significantly increased with increasing polymer concentration. Higher polymer load also increased the thickness of internal polymer network, which led to reduced drug loss and higher entrapment efficiency (89%). The cumulative in vitro release was found to be in the range of 54.96 to 99.36% during the release studies (12 h) following zero order release kinetics and non-Fickian diffusion pattern. The developed microparticles have the potential to sustain the release of ropinirole, which may lead to a reduction in its adverse effects and improved management of Parkinson's disease.

Nebivolol-Loaded Microsponge Gel for Healing of Diabetic Wound.

An attempt was made to formulate nebivolol-loaded microsponge gel to access drug at wound area, incorporated into gel that possess optimum moist wound management environment during later stages of wound closure. Nebivolol, antihypertensive drug, exhibits vasodilating effects via nitric oxide pathway, slows diabetic neuropathy, and restores endothelial function in diabetic wounds. Microsponges were prepared by optimizing independent variables; drug to polymer ratio and internal phase volume and their effects on production yield, entrapment efficiency, and particle size. Formulations of microsponges were evaluated for drug content. Differential scanning calorimetry indicated reduction in crystallinity of NB during the formation of microsponges. In vitro study (drug to polymer 1:4 and 10 ml internal phase volume acetone) showed 80% drug released within 8 h. Spherical and porous microsponges confirmed by scanning electron microscopy were incorporated in the carbopol 934 (2%) gel base. Gel was characterized for pH, viscosity, and drug content. Less spreadability determined by texture analyzer demonstrated viscous nature of gel. In vitro diffusion study revealed entrapped drug in porous microsponges with slow release to heal wound. In vivo study performed using streptozotocin-induced diabetic rats and excision wound model showed wound healing and closure activity within day 10. Histology revealed inflammatory cell infiltrations and neovascularization in granulation tissues, ultimately healing wound. Microsponge gel prolonged drug release due to entrapped form in porous structure of microsponges with significant and fast wound healing and closure in diabetic rats. Microsponges with loaded drug fulfilled accessibility at wound area, while gel provided optimum moist wound management environment during later stages of wound closure.

Drug Release and Targeting: the Versatility of Polymethacrylate Nanoparticles for Peroral Administration Revealed by Using an Optimized In Vitro-Toolbox.

PURPOSE: The contribution of permeability and drug release to drug targeting were investigated in the course of development of a nanosized formulation of the anti-inflammatory compound TMP-001, for the local treatment in the gastrointestinal tract. METHODS: TMP-001 was encapsulated by nanoprecipitation into Eudragit® RS 100. The permeability of these carriers was investigated in an Ussing chamber model and the release rate was determined under biorelevant conditions. Formulation toxicity and particle-cell-interaction were investigated by flow cytometry, fluorescence and electron microscopy. Furthermore, spray drying was performed. RESULTS: Effective internalization of Eudragit®-nanoparticles into cancer cells was demonstrated. A burst release of the nanoparticles implied poor interaction of TMP-001 with Eudragit®. A sustained release (70.5% release after 30 min compared to 98.0% for the API) was accomplished after spray drying yielded an increased particle size. Recovery rate of TMP-001 after spray drying was 94.2 ± 5.9%. CONCLUSION: The release of API from polymeric nanoparticles contributes profoundly to the in vivo-performance of drug delivery devices in the gastrointestinal tract. The impact of drug-polymer interaction and particle size was analyzed. Sustained release of TMP-001 could only be achieved by increasing particle size. Therefore, biorelevant release testing has been demonstrated to be a valid tool for nanoformulation design.

Nanosponge-based pediatric-controlled release dry suspension of Gabapentin for reconstitution.

CONTEXT: Gabapentin was selected to formulate oral controlled release dry suspension because of short biological half life of 5-7 h and low bioavailability (60%). Gabapentin is a bitter drug so an attempt was made to mask its taste. OBJECTIVE: To formulate and evaluate controlled release dry suspension for reconstitution to increase the bioavailability and to control bitter taste of drug. MATERIALS AND METHODS: Cyclodextrin based nanosponges were synthesized by previously reported melt method. The nanosponge-drug complexes were characterized by FTIR, DSC and PXRD as well as evaluated for taste and saturation solubility. The complexes were coated on Espheres by a suspension layering technique followed by coating with ethyl cellulose and Eudragit RS-100. A dry powder suspension for reconstitution of the microspheres was formulated and evaluated for taste, redispersibility, in vitro dissolution, sedimentation volume, leaching and pharmacokinetics. RESULTS AND DISCUSSION: The complexes showed partial entrapment of drug nanocavities. Significant decrease in solubility (25%) was observed in the complexes than pure drug in different media. The microspheres of nanosponge complexes showed desired controlled release profile for 12 h. Insignificant drug leaching was observed in reconstituted suspension during storage for 7 days at 45 °C/75% RH. Nanosponges effectively masked the taste of Gabapentin and the coating polymers provided controlled release of the drug and enhanced taste masking. The results of in vivo studies showed increase in bioavailability of controlled release suspension by 24.09% as compared to pure drug. CONCLUSION: The dry powder suspension loaded with microspheres of nanosponges complexes can be proposed as a suitable controlled release drug delivery for Gabapentin.

Statistical optimization of controlled release microspheres containing cetirizine hydrochloride as a model for water soluble drugs.

The purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 3(3) Box-Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348 µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0-∞ value of 3309 ± 211 ng h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets.

Design, statistical optimisation, characterisation and pharmacodynamic studies on Pioglitazone hydrochloride floating microparticles.

The purpose of this study was to develop floating microparticles containing Pioglitazone HCl, for controlled release and perform pharmacodynamic studies. The FTIR and DSC studies revealed that there is no interaction between drug and excipients used. The 2(2) factorial design was employed to evaluate the effect of drug: polymer (total) and Eudragit RS 100: Eudragit RL 100. The floating microparticles were prepared by solvent evaporation technique. The predicted and actual values of drug release at 1 h, 8 h and drug entrapment were 38.307%, 77.76%, 84.25% and 38.712%, 76.237% and 84.62%, respectively. XRD and SEM studies showed reduced crystallinity of drug and spherical microparticles. Buoyancy studies revealed good floating of particles for 12 h. Pharmacodynamic studies showed significant reduction in blood glucose levels in male New Zealand rabbits. The results demonstrate the feasibility of the factorial design in successfully developing floating microparticles of Pioglitazone HCl for controlled release.

Protective efficacy of ursodeoxycholic acid nanoparticles in animal model of inflammatory bowel disease.

UNLABELLED: Abstract Context: Ursodeoxycholic acid (UDCA) exerts dose-dependent chemoprevention in colonic inflammation. Polycationic UDCA nanoparticles (UNPs) are envisaged for solubility enhancement and site directed drug delivery. OBJECTIVE: The objective was to study the ameliorative efficacy of UNPs through localized delivery of the drug. METHODS: UNPs were prepared through nanoprecipitation technique. Particle size, morphology, in vitro drug release and in vivo protective efficacy in inflammatory bowel disease (IBD) of these nanoparticles were studied. RESULTS AND DISCUSSION: The average particle size was around 100 nm, and the average drug encapsulation was about 99%. In vitro drug release study shows optimal drug release in simulated colonic fluid. The lowering of tissue nitric oxide, malondialdehyde, myeloperoxidase and histology of the colon tissue supported the protective efficacy of the nanoparticles. CONCLUSION: This study presents the improved efficacy of UNPs in animal model of IBD due to complete release of drug at the desired site of action.

Development of 4-phenylbutyric acid microsponge gel formulations for the treatment of lewisite-mediated skin injury.

Lewisite, a chemical warfare agent, causes skin blisters, erythema, edema, and inflammation, requiring mitigation strategies in case of accidental or deliberate exposure. 4-phenyl butyric acid (4-PBA), a chemical chaperone, reduces endoplasmic reticulum stress and skin inflammation. The study aimed to encapsulate 4-PBA in microsponges for effective, sustained delivery against lewisite injury. Porous microsponges in a topical gel would potentially sustain delivery and improve residence time on the skin. Microsponges were developed using the quasi-emulsion solvent diffusion method with Eudragit RS100. Optimized formulation showed 10.58%w/w drug loading was incorporated in a carboxymethylcellulose (CMC) and Carbopol gel for in vitro release and permeation testing using dermatomed human skin. A sustained release was obtained from all vehicles in the release study, and IVPT results showed that compared to the control (41.52 ± 2.54 µg/sq.cm), a sustained permeation profile with a reduced delivery was observed for microsponges in PBS (14.16 ± 1.23 µg/sq.cm) along with Carbopol 980 gel (12.55 ± 1.41 µg/sq.cm), and CMC gel (10.09 ± 1.23 µg/sq.cm) at 24 h. Optimized formulation showed significant protection against lewisite surrogate phenyl arsine oxide (PAO) challenged skin injury in Ptch1+/-/SKH-1 hairless mice at gross and molecular levels. A reduction in Draize score by 29%, a reduction in skin bifold thickness by 8%, a significant reduction in levels of IL-1ß, IL6, and GM-CSF by 54%, 30%, and 55%, respectively, and a reduction in apoptosis by 31% was observed. Thus, the translational feasibility of 4-PBA microsponges for effective, sustained delivery against lewisite skin injury is demonstrated.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration.

Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400-500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-ß-CD as a cryoprotectant. It ensured the preservation of the NPs' size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities.

Tamoxifen-Loaded Eudragit Nanoparticles: Quality by Design Approach for Optimization of Nanoparticles as Delivery System.

Nanoparticles have numerous applications as drug carriers in drug delivery. The aim of the study was to produce tamoxifen nanoparticles with a defined size and higher encapsulation for efficient tissue uptake with controlled drug release. The quality by design approach was utilized to produce tamoxifen-loaded Eudragit nanoparticles by identifying the significant process variables using the nanoprecipitation method. The process variables (amount of drug, polymer, and surfactant) were altered to analyze the influence on particle size (PS), % encapsulation efficiency (EE). The results showed that the drug and polymer individually as well as collectively have an impact on PS, while the surfactant has no impact on the PS. The %EE was influenced by the surfactant individually and in interaction with the drug. The linear regression model was endorsed to fit the data showing high R2 values (PS, 0.9146, %EE, 0.9070) and low p values (PS, 0.0004, EE, 0.0005). The PS and EE were confirmed to be 178 nm and 90%, respectively. The nanoparticles were of spherical shape, as confirmed by SEM and TEM. The FTIR confirmed the absence of any incompatibility among the ingredients. The TGA confirmed that the NPs were thermally stable. The in vitro release predicted that the drug release followed Higuchi model.

Moxifloxacin loaded nanoparticles of disulfide bridged thiolated chitosan-eudragit RS100 for controlled drug delivery.

The aim of our study was to prepare nanoparticles of disulfide bridged thiolated chitosan and eudragit RS100 using the air oxidation method for controlled drug delivery. The developed nanoparticles were characterized by FTIR, DSC, TGA, zeta sizer, zeta potential, SEM and 1H NMR. The loading, entrapment efficiency and in-vitro release of moxifloxacin from nanoparticles was determined. Toxicity was studied using Caco-2 cell line and pharmacokinetics of moxifloxacin from the developed nanoparticles was studied in albino rats. The FTIR analysis showed no chemical interaction of the drug with the thiolated polymers. The DSC and TGA showed the thermal stability of nanoparticles. The average particle size of nanoparticles was 87 nm, zeta potential of NTC3 was ± 19 and SEM showed the spherical shape of nanoparticles. The 1H NMR spectra confirmed the structure of thiolated chitosan and eudragit RS100. The loading, encapsulation efficiency and release of moxifloxacin from NTC3 were 100.3%, 89.67% and 88.49% respectively. The nanoparticles in culture medium did not affect the viability of Caco-2 cells. The NTC3 formulation showed a greater bioavailability of moxifloxacin compared to the reference formulation. The study reports a convenient and effective way to prepare a chitosan and eudragit RS100 based drug delivery system with a controlled release pattern.

Eudragit-Coated Sporopollenin Exine Microcapsules (SEMC) of Phoenix dactylifera L. of 5-Fluorouracil for Colon-Specific Drug Delivery.

In this study, 5-fluorouracil (5-FU)-loaded pollens of Phoenix dactylifera and their coating with ERS was done and evaluated for the colon-targeted delivery of 5-FU to treat colon cancer. Sporopollenin exine microcapsules (SEMC) from the pollens of Phoenix dactylifera were extracted by the reflux method and 5-FU into SEMC was encapsulated by the vacuum-assisted loading method. 5-FU loaded SEMC was coated with Eudragit® RS-100 (ERS) by the organic solvent-evaporation technique under vacuum to avoid the discharge of 5-FU in the stomach and small intestine. Morphological and physicochemical characterization of drug-loaded SEMC (coated/uncoated) was performed by scanning electron microscopy (SEM), FTIR, XRD, and DSC. The encapsulation and drug loading were determined by the direct method, and an in vitro release study was performed in simulated gastric and intestinal fluids (SGF/SIF). The colon-specific delivery of 5-FU from the SEMC was assessed in terms of pharmacokinetics and gastrointestinal tract distribution after oral administration in rats. The successful encapsulation and loading of 5-FU into SEMC by a vacuum-assisted loading technique and its coating with ERS by a solvent-evaporation technique were achieved. SEM images of uncoated SEMC have shown porous structures, and coating with ERS reserved their morphology with a smooth surface and discrete microstructures and the 5% w/v ERS acetone solution. ERS-coated SEMC sustained the release of 5-FU until 24 h in SIF, while it was up to 12 h only from uncoated SEMC. The maximum plasma concentration (Cmax) of 5-FU from uncoated SEMC was 102.82 µg/mL after 1 h, indicating a rapid release of 5-FU in the upper gastrointestinal tract. This concentration decreased quickly with a half-life of 4 h, AUC0-t was 264.1 µg/mL.h, and MRT0-inf was 5.2 h. The Cmax of 5-FU from ERS-coated SEMC was 19.47 µg/mL at 16 h. The Cmax of 5-FU in small intestines was 406.2 µg/g at 1 h from uncoated SEMC and 1271.5 µg/g at 12 h from coated SEMC. Conclusively, a 249.9-fold higher relative bioavailability of 5-FU was achieved with the ERS-coated SEMC in colon tissues than that from uncoated SEMC.

Nanosuspension as an Efficient Carrier for Improved Ocular Permeation of Voriconazole.

BACKGROUND: The present limitations related to the ocular administration of antifungal drugs for the treatment of fungal keratitis include poor ocular bioavailability, limited retention time, and low ocular tissue penetration. METHODS: This study aimed to prepare a novel ophthalmic voriconazole-loaded nanosuspension based on Eudragit RS 100. Pharmasolve® was explored as a corneal permeation enhancer in voriconazole ophthalmic formulation using in vitro and in vivo experiments. Briefly, 1% voriconazole-loaded nanosuspension was prepared using the quasi-emulsion solvent evaporation process. RESULTS: Characterizations of the voriconazole-loaded nanosuspension by Zetasizer Nano ZS and Transmission Electron Microscope (TEM) showed a uniform spherical shape without any agglomeration. The well-discreted nanoparticle with a size of 138 ± 1.3 nm was achieved with high entrapment efficiency (98.6 ± 2.5%) and positive zeta potential in the range of 22.5-31.2mV, indicating excellent physical stability. DISCUSSION: Voriconazole-loaded nanosuspension containing the penetration enhancer displayed good permeability both in vitro and in vivo compared with the commercial voriconazole injection. The voriconazole-loaded nanosuspension exhibited good antifungal activity, significantly inhibiting the growth of Candida albicans at a lower concentration of voriconazole (2.5µg/mL, p < 0.05). CONCLUSION: In conclusion, the voriconazole-loaded nanosuspension containing Pharmasolve® can be used as an effective ophthalmic formulation for the topical ocular delivery of voriconazole.

Curcumin-loaded nanocapsules: Influence of surface characteristics on technological parameters and potential antimalarial activity.

The present study aimed to develop nanocapsules (NCs) loaded with curcumin (CCM) using different coatings, comparing the effect of these coatings on physicochemical properties of NCs. NCs were prepared by interfacial deposition of performed polymer, using different polymers as coatings (P80, PEG, Chitosan and Eudragit RS100®) and then, characterized in detail by different techniques (AFM, FTIR, DSC, XRD, among others). In vitro studies were performed, evaluating the release profile, cytotoxicity and antimalarial activity of CCM-loaded NCs. Overall, all CCM-loaded NCs samples exhibited typical characteristics as nanometric size, coating-dependent zeta potential, acidic pH value, span values below 2, homogeneous morphology and CCM-distribution in pseudophases of type VI (for all of coatings). Experimental results showed that CCM remains stable in lipid-core of NCs, maintaining its physicochemical and biological properties after nanoencapsulation process. In vitro release assays showed that nanoencapsulation was an efficient strategy to controlled release of CCM and P80-coated NCs presented slowest CCM-release considering all nanoformulations tested. Still, CCM-loaded NCs presented no cytotoxic effect. Also, all CCM-loaded NCs showed a perceptible antimalarial activity independently of their coatings (anionic and cationic), with more expressive results for CS-coated NCs. In conclusion, findings for CCM-loaded NCs and their different coatings seem to be a promising strategy to improve your biological activity.