Ceramide and N,N,N-Trimethylphytosphingosine-Iodide (TMP-I)-Based Lipid Nanoparticles for Cancer Therapy.

Purpose: To evaluate the anti-tumor effect of ceramide or trimethylphytosphingosine-iodide (TMP-I) containing solid lipid nanoparticles (SLNs) prepared using trymyristin, phosphatidylcholine (PC), and Pluronic P85 (P85) for intravenous delivery of docetaxel.

Methods: Docetaxel-loaded SLNs using ceramide or TMP-I at 3.22% (w/w) with a mean diameter of 89-137 nm were successfully prepared by high pressure homogenization.

Carbopol-incorporated thermoreversible gel for intranasal drug delivery.

The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-β-cyclodextrin (HP-β-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were characterized by gelation temperature, viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel was demonstrated by rheological studies.

Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate.

The intention of this study was to compare the physicochemical properties, stability and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD) and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared by a surface attached method using different ratios of Cremophor RH60 (surfactant) and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP).

AAPE proliposomes for topical atopic dermatitis treatment.

Context: Anti-inflammatory effect of advanced adipose stem cell derived protein extract (AAPE) could be improved by minimising protein degradation.

Objective: To develop a proliposomal formulation of AAPE for the treatment of topical atopic dermatitis.

Materials And Methods: Proliposomal powder was manufactured by evaporating a solution of soy phosphatidyl choline, AAPE and Poloxamer 407 in ethanol under vacuum on sorbitol powder.

Polymeric nanocapsules with SEDDS oil-core for the controlled and enhanced oral absorption of cyclosporine.

Self-microemulsifying drug delivery system (SEDDS) cored-polymeric nanocapsules (NC) were fabricated using emulsion diffusion method for the controlled oral absorption of the poorly water soluble drug, cyclosporine. Poly-dl-lactide (PDLLA) was used as the shell-forming polymer. The NCs in different polymer/oil ratios (from 25/125 to 125/125) were prepared following a solvent-diffusion method.

A novel lipid nanoemulsion system for improved permeation of granisetron.

A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50 nm with PI<0.

Inclusion complex effect on the bioavailability of clotrimazole from poloxamer-based solid suppository.

To study the effect of β-cyclodextrin (βCD) inclusion complex on the bioavailability of clotrimazole from poloxamer-based suppository, formulations composed of P 188, propylene glycol and different molar ratio of clotrimazole-βCD inclusion complex were prepared. Clotrimazole (1%) has been formulated in a suppository using the thermo sensitive polymer P188 (70%) together with propylene glycol (30%). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex at various molar ratios with βCD (1:0.

A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation.

This study describes a novel carrier, transethosome, for enhanced skin delivery of voriconazole. Transethosomes (TELs) are composed of phospholipid, ethanol, water and edge activator (surfactants) or permeation enhancer (oleic acid). Characterization of the TELs was based on results from recovery, particle size, transmission electron microscopy (TEM), zeta potential and elasticity studies.

Cross-linked hyaluronic acid-based flexible cell delivery system: application for chondrogenic differentiation.

A flexible porous three-dimensional (3D) matrix of hyaluronic acid (HA) was developed to improve the rigidity problems of the previously developed 3D systems. The viscoelasticity of the new formulation was expected to facilitate the differentiation of chondrocytes for the treatment of osteoarthritis (OA). The 3D matrix was fabricated using poly (ethylene glycol) diglycidyl ether (PEGDG) as a cross-linker, which was identified by Fourier transform infrared spectroscopy (FT-IR).

Interpenetrating polymer network (IPN) scaffolds of sodium hyaluronate and sodium alginate for chondrocyte culture.

In this study, porous sodium hyaluronic acid/sodium alginate (HA/SA) scaffold based on interpenetrating polymeric network (IPN) technique has been fabricated, where HA and SA were cross-linked with poly(ethylene glycol) diglycidyl ether (PEGDG) and calcium chloride, respectively. The mean pore size and the swelling ratio of fabricated scaffolds decreased, and the compressive strength increased as the content of SA increased in HA/SA IPN scaffold. Rabbit chondrocytes were seeded within the HA/SA IPN scaffolds, and then their proliferation as well as chondrogenic differentiation was examined.

Evaluation of protein stability and in vitro permeation of lyophilized polysaccharides-based microparticles for intranasal protein delivery.

Biocompatible microparticles prepared by lyophilization were developed for intranasal protein delivery. To test for the feasibility of this formulation, stability of the incorporated protein and enhancement of in vitro permeation across the nasal epithelium were evaluated. Lyophilization was processed with hydroxypropylmethylcellulose (HPMC) or water soluble chitosan (WCS) as biocompatible polymers, hydroxypropyl-β-cyclodextrin (HP-β-CD) and d-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) as permeation enhancers, sugars as cryoprotectants and lysozyme as the model protein.

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein.

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS.

Evaluation of salicylic acid fatty ester prodrugs for UV protection.

The purpose of this study was to investigate the physicochemical properties and in vitro evaluation of fatty ester prodrugs of salicylic acid for ultraviolet (UV) protection. The physicochemical properties such as lipophilicity, chemical stability and enzymatic hydrolysis were investigated with the following fatty ester prodrugs of salicylic acid: octanoyl (C8SA), nonanoyl (C9SA), decanoyl (C10SA), lauroyl (C12SA), myristoyl (C14SA) and palmitoyl oxysalicylate (C16SA). Furthermore, their skin permeation and accumulation were evaluated using a combination of common permeation enhancing techniques such as the use of a lipophilic receptor solution, removal of stratum corneum and delipidization of skin.

Effect of process parameters on nanoemulsion droplet size and distribution in SPG membrane emulsification.

A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/water (O/W) nanoemulsion of flurbiprofen consisting of methylene chloride as the dispersed phase, polyvinyl alcohol (PVA) as the stabilizer and a mixture of Tween 20 and Tween 80 in demineralized water as the continuous phase. Emulsion droplets with a mean droplet size of 25 times smaller than the mean pore size and a narrow droplet size distribution were produced using 5% emulsifier at a feed pressure of 15 kPa.

Poloxamer/cyclodextrin/chitosan-based thermoreversible gel for intranasal delivery of fexofenadine hydrochloride.

To enhance permeation and solubility of an intranasal delivery system of fexofenadine hydrochloride (FXD HCl), a new formulation using poloxamer 407 (P407)/hydroxypropyl-β-cyclodextrin (HP-β-CD)-based thermoreversible gels with chitosan, was developed. Prepared gels were characterized by gelation temperature, viscosity, viscoelasticity, and drug release profile. The in vitro permeation study was performed in primary human nasal epithelial cell monolayers cultured by air-liquid interface method.

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability.

To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction.

Characterization and in vitro evaluation of freeze-dried microparticles composed of granisetron-cyclodextrin complex and carboxymethylcellulose for intranasal delivery.

The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal delivery. The composition of MPs was determined from the phase-solubility study of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GRN and excipients.

Preparation and evaluation of fexofenadine microemulsion for intranasal delivery.

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats.

Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil).

Preparation and evaluation of fexofenadine microemulsions for intranasal delivery.

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats.

Rheological characterization and in vivo evaluation of thermosensitive poloxamer-based hydrogel for intramuscular injection of piroxicam.

To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel.

Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein.

Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant.

Enhanced oral bioavailability of flurbiprofen by combined use of micelle solution and inclusion compound.

The main purpose of this study was to evaluate the effect of a mixed drug solution containing a surfactant and beta-cyclodextrin (beta-CD) on the solubility and bioavailability of a poorly water soluble drug, flurbiprofen. Solubility, dissolution and in vivo pharmacokinetics of flurbiprofen in the presence of surfactant, beta-CD or mixture of surfactant and beta-CD were investigated. Among the surfactants tested, Tween 80 produced the highest improvement in the aqueous solubility of flurbiprofen.

The effects of mixed MPEG-PLA/Pluronic copolymer micelles on the bioavailability and multidrug resistance of docetaxel.

A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic copolymers was developed for enhanced bioavailability and to overcome multidrug resistance of docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized docetaxel were evaluated for the effect of Pluronic copolymers weight ratio on the mixed micelles with respect to drug loading and drug release. In vitro, cell viability and cytotoxicity studies in KB and KBv cells revealed that the mixed micellar formulations were more potent than the commercial docetaxel formulation (Taxotere).

Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems.

To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90).