Improved Drug Loading Capacity Research Articles

Hyaluronic Acid Scaffolds and Injectable Gels for Healing of Induced Arthritis in Rat Knee: Effect of Prednisolone Revisited

Considering the absence of a definite cure for osteoarthritis and problems of existing approaches, designing scaffolds for cartilage regeneration by tissue engineering methods seems necessary. Optimization of scaffolds properties is one of the biggest challenges in this area. Due to contradicting reports regarding efficacy and safety of intra-articular injections of corticosteroids, further evaluation of these agents by their incorporation into a designed scaffold could be beneficial. On this basis, a hyaluronic acid (HA) scaffold was designed in two forms: shear-thinning injectable gel and lyophilized implantable disk. Polyethylene glycol diglycidyl ether (PEGDGE) was used as cross-linker. After optimization of scaffolds properties, in vivo efficacy of the most optimum formulation (HA 2%, PEGDGE 0.5%) in the presence and absence of prednisolone (0.1% W/V) was evaluated. In vivo studies in rats showed that after 10 weeks, HA scaffolds, in both forms, repaired damaged articular cartilage to some extent but incorporation of prednisolone into the scaffold showed no additional benefit. Overall it seems that implantable scaffolds of HA could be a potential therapeutic choice for cartilage regeneration and corticosteroids in long term may also reverse these beneficial effects. Hyaluronic acid (HA) is one of the major components of the extracellular matrix and cartilage tissue. There are numerous reports on the efficacy of different scaffolds of HA for cartilage regeneration. New engineering methods focus on retaining the scaffolds in the site for long time as well as loading therapeutic agents to accelerate the healing process. In situ injection of corticosteroids is one of the routine interventions for osteoarthritis. Here, the effect of loading prednisolone as an anti-inflammatory agent into the shear thinning gels and implantable disks of HA for treatment of an induced arthritis in rat knee was revisited. In future studies we will upgrade the scaffold by mixing HA with some other biopolymers to increase the strength and retention of the system and to improve drug loading capacity. It seems that loading specific growth factors would be an alternative to corticosteroids with higher efficacy and lower side effects.

A Novel Technique to Improve Drug Loading Capacity of Fast/Extended Release Orally Dissolving Films with Potential for Paediatric and Geriatric Drug Delivery.

Orally dissolving films (ODFs) have received much attention as potential oral drug delivery systems for paediatric and geriatric patients, particularly those suffering from dysphagia. With their unique properties and advantages, the technology offers improved patient compliance and wider acceptability, eliminates the fear of choking, enables ease of administration and offers dosing convenience, without the requirement of water. However, adequate drug loading remains a challenge. The aim of this study was to mechanistically design and evaluate fast and extended release ODF formulations with high drug loading capacity, displaying good physicochemical and mechanical properties, as a potential dosage form for paediatric and geriatric use employing a slightly soluble model drug-ibuprofen. Different polymers (0.6-10% HPMC, 0.6-1.5% guar gum), plasticisers (0.1-0.5% glycerine, 0.1% sorbitol) and processing conditions (40-60°C drying temperatures, 8-16h drying times) were investigated to produce films using the solvent casting method. Molecular compatibility was assessed using TGA, XRD and FTIR whereas film topography was assessed using SEM. Maximum ibuprofen load in single films was 20.7mg/film (54.4%) and released 100% drug content in 5min, while triple layered ibuprofen-loaded films contained 62.2mg/film and released 100% drug release in 1h. The ODFs demonstrated good disintegration time using low volume artificial saliva media and high dosage from uniformity. This study provides a mechanistic insight to the design and evaluation of fast and extended release ODFs with high drug loading, suitable for administration to paediatric and geriatricpatients.

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review.

The efficacy of current standard chemotherapy is suboptimal due to the poor solubility and short half-lives of chemotherapeutic agents, as well as their high toxicity and lack of specificity which may result in severe side effects, noncompliance and patient inconvenience. The application of nanotechnology has revolutionized the pharmaceutical industry and attracted increasing attention as a significant means for optimizing the delivery of chemotherapeutic agents and enhancing their efficiency and safety profiles. Nanostructured lipid carriers (NLCs) are lipid-based formulations that have been broadly studied as drug delivery systems. They have a solid matrix at room temperature and are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsions, liposomes and solid lipid nanoparticles (SLNs) due to their enhanced physical stability, improved drug loading capacity, and biocompatibility. This review focuses on the latest advances in the use of NLCs as drug delivery systems and their preparation and characterization techniques with special emphasis on their applications as delivery systems for chemotherapeutic agents and different strategies for their use in tumor targeting.

Magnetic nano carboxymethyl cellulose-alginate/chitosan hydrogel beads as biodegradable devices for controlled drug delivery

For the first time, nano carboxymethyl cellulose (NCMC) was synthesized via cellulose nanocrystal carboxymethylation. This nanomaterial was magnetized and used in bilayer alginate-chitosan hydrogel beads formulation to develop eco-friendly, smart, and magnetic sensitive hydrogel beads for the controlled pH-sensitive release of dexamethasone as a model drug. Water-soluble nanocrystalline cellulose (NCMC) and bilayer hydrogel beads were characterized in terms of size, surface morphology, surface modification, crystallinity, drug loading content, and in vitro drug release profile using various technics. Furthermore, the swelling behavior of hydrogels was examined and reported in three buffer media. The NCMCs improved drug loading capacity and swelling properties and also regulated drug release behavior of hydrogels. The hydrogel beads swelling specification exhibited a higher index in phosphate buffer at pH 5.8 than at pH 1.2 and 7.4. Besides, in vitro release of beads revealed excellent pH-sensitive drug release profiles and prevented release in the gastrointestinal tract. The beads showed high pH sensitivity for dexamethasone drug in pH 5.8 in compared to other pH media. The obtained results could introduce hydrogel beads as a high potential drug delivery system.

Design and Characterization of Nanostructure Lipid Carrier for Transdermal Delivery of Pioglitazone

Nanostructure Lipid Carrier (NLC) is one of the lipid-based drug delivery systems that are used as carrier for delivery of drugs. NLC are composed of mixture of solid lipid and liquid lipid, which form imperfect type of lipid matrix with improved drug loading capacity, drug release profile and stability. The aim of the present study was to develop and characterize nanostructure lipid carrier for transdermal delivery of pioglitazone (PZ) to overcome the problems related with oral route of administration and to improve systemic availability. NLC’s were prepared by high-speed homogenization method. Optimized NLC formulation was evaluated for particle size, percentage entrapment efficiency, surface morphology, DSC analysis, in-vitro drug release etc. The optimized NLC formulation was formulated as a transdermal patch and evaluated for in vitro drug release study and primary skin irritation study. In vivo hypoglycaemic activity of pioglitazone -NLC loaded transdermal patch was studied in comparison with its orally administered suspension. PZ- NLC loaded transdermal patch was found to be non-irritant and showed reduction in blood glucose level in a controlled manner up to 24 hrs.

Magnesium lithospermate B loaded PEGylated solid lipid nanoparticles for improved oral bioavailability

Magnesium lithospermate B (MLB) is an active polyphenol acid with multiple pharmacological activities and poor oral bioavailability. The present research aimed to construct MLB loaded solid lipid nanoparticles (MLB-SLNs) for oral delivery to enhance its bioavailability. MLB-SLNs were prepared by solvent diffusion method and subsequently modified with polyethylene glycol monostearate (PEG-SA) superficially. The particle sizes of MLB-SLNs varied from 82.57 to 53.50nm with an improved drug loading capacity (up to 16.18%) after PEG-SA modification. Pharmacokinetic study indicated that Cmax (peak plasma MLB concentration) and AUC (area under curve) of MLB-SLNs increased significantly compared to that of MLB solution in male SD rats. The relative bioavailability of MLB-SLNs with PEG-SA modification was 753.98% compared to MLB solution administered by tail intravenous injection. The enhanced transport mechanism could be further illustrated by the results that MLB-SLNs showed higher permeability across Madin-Daby canine kidney (MDCK) epithelial cell monolayer and MLB-SLNs with smaller particle size distribution and PEG-SA modification manifested stronger cellular internalization ability on MDCK cells. Thus, PEG-SA modified solid lipid nanoparticles confirmed with enhanced cellular transport and improved oral bioavailability can be a promising oral MLB delivery system.

Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(e-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

Real-time near-infrared bioimaging of a receptor-targeted cytotoxic dendritic theranostic agent.

Efficient and site-specific delivery of anticancer drugs to tumors is important in the development of effective cancer chemotherapy. As an undecapeptide of the tachykinin neuropeptide family, the substance P (SP)/neurokinin-1 receptor (NK1R) system has been identified as a promising ligand-receptor pair in tumor-specific drug delivery. However, the rational design of suitable theranostic agents with high drug loading capacity and tumor targeting for cancer patients remains a great challenge. Herein, we report a dendritic strategy that utilizes the two amine functionalities of lysine to create branch points that allow conjugation of the anticancer drug 5-fluorouracil (5-FU) to the tumor-targeting ligand substance P, along with an additional near-infrared (NIR) squaraine dye, to construct a theranostic dendritic agent, P-FU 4. This cytotoxic theranostic agent, containing four carboxyl-modified 5-FU molecules, has several desirable advantages: i) the ability to self-assemble into nanoparticles; ii) enhanced cytotoxicity with high drug loading capacity (16%) and a specific receptor-targeted interaction with NK1R through the SP moiety; and iii) a high NIR squaraine fluorescence efficiency due to the specific dendron isolation, avoiding aggregation-mediated quenching. As demonstrated in this report, the cytotoxic activity of P-FU 4 is dose-dependent against the tested cancer cells. The improved drug loading capacity with dendritic branching distinctly enhanced cytotoxicity to tumor cells but had little effect on the viability of normal cells. P-FU 4 was preferentially taken up by tumor cells through a receptor-mediated interaction, which was monitored by effective NIR fluorescence with high tissue penetration. Studies using a mouse model revealed that P-FU 4 can significantly inhibit tumor progression, with a tumor-inhibition rate of 60.2%. The receptor-targeted cytotoxic dendritic theranostic agent is highly preferable to standard chemotherapeutic treatments and decreases the negative side effects of medications on healthy cells, which establishes its utility in drug delivery and cancer chemotherapy.

Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery – a comparison with solid lipid particles

Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01™, Geleol™ and Gelucire 50/13™. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01™:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity.

Drug loading optimization and extended drug delivery of corticoids from pHEMA based soft contact lenses hydrogels via chemical and microstructural modifications

This paper proposes an approach to improve drug loading capacity and release properties of poly(2-hydroxyethyl methacrylate) (p(HEMA)) soft contact lenses based on the optimization of the hydrogel composition and microstructural modifications using water during the polymerization process.P(HEMA) based soft contact lenses were prepared by thermal or photopolymerization of 2-hydroxyethyl methacrylate (HEMA) solutions containing ethylene glycol di-methacrylate as crosslinker and different proportions of N-vinyl-2-pyrrolidone (NVP) or methacrylic acid (MA) as co-monomers. Transmittance, water uptake, swelling, microstructure, drug absorption isotherms and in vitro release were characterized using triamcinolone acetonide (TA) as model drug. Best drug loading ratios were obtained with lenses containing the highest amount (200mM) of MA. Incorporation of 40% V/V of water during the polymerization increases the hydrogel porosity giving a better drug loading capacity.In vitro TA release kinetics shows that MA hydrogels released the drug significantly faster than NVP-hydrogels. Drug release was found to be diffusion controlled and kinetics was shown to be reproducible after consecutive drug loading/release processes. Results of p(HEMA) based soft contact lenses copolymerized with ethylene glycol dimethacrylate (EGDMA) and different co-monomers could be a good alternative to optimize the loading and ocular drug delivery of this corticosteroid drug.

Functionalization of Hollow Mesoporous Silica Nanoparticles for Improved 5‐FU Loading

Hollow mesoporous silica nanoparticles were successfully fabricated and functionalized with appropriate silanes. After modifications, amine, carboxyl, cyano, and methyl groups were grafted onto the nanoparticles and all functionalized hollow mesoporous silica nanoparticles maintained a spherical and hollow structure with a mean diameter of ~120 nm and a shell thickness of ~10 nm. The loading capacity of the hollow mesoporous silica nanoaprticles to the anticancer drug, 5‐fluorouracil, can be controlled via precise functionalization. The presence of amine groups on the surface of nanoparticles resulted in the highest loading capacity of 28.89%, due to the amine functionalized nanoparticles having a similar hydrophilicity but reverse charge to the drug. In addition, the change in pH leads to the variation of the intensity of electrostatic force between nanoparticles and the drug, which finally affects the loading capacity of amine functionalized hollow mesoporous silica nanoparticles to some extent. Higher drug loading was observed at pH of 7.4 and 8.5 as 5‐fluorouracil becomes more deprotonated in alkaline conditions. The improved drug loading capacity by amine functionalized hollow mesoporous silica nanoparticles has demonstrated that they can become potential intracellular 5‐fluorouracil delivery vehicles for cancers.

Fe3O4@carbon@zeolitic imidazolate framework-8 nanoparticles as multifunctional pH-responsive drug delivery vehicles for tumor therapy in vivo.

Controlled drug release is a promising approach for cancer therapy due to its merits of reduced systemic toxicity and enhanced antitumor efficacy. Here, multifunctional Fe3O4@carbon@zeolitic imidazolate framework-8 (FCZ) hybrid nanoparticles (NPs) were successfully constructed. Owing to the porosity and acid-sensitivity of zeolitic imidazolate framework-8 (ZIF-8), FCZ NPs not only displayed an improved drug loading capacity compared to most of the polymeric nanocarriers, but also exhibited excellent pH-triggered release of doxorubicin (DOX) in vitro. Moreover, carbon dots (CDs) embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals could simultaneously function as intracellular fluorescence imaging and T2*-weighted magnetic resonance imaging (MRI) contrast agents, respectively. The results obtained from the MTT assay demonstrated good biocompatibility of FCZ NPs. DOX release experiments showed pH regulation-dominated drug release kinetics: a weak acidic pH in tumor areas could trigger sustained drug release, suggesting that FCZ NPs are ideal drug delivery systems. Moreover, the remarkable inhibition of tumor growth without side effects was confirmed in vivo. These results provide convincing evidence establishing the multifunctional FCZ NPs as promising candidates for tumor therapy.

Influence of formulation parameters on the physicochemical properties of meloxicam-loaded solid lipid nanoparticles

Objective The aim of this research was to investigate novel particulate carrier systems such as solid lipid nanoparticles (SLNs) for topical delivery of a lipophilic drug, meloxicam (MLX). Methods MLX-loaded SLNs were prepared using a modified high-shear homogenization and ultrasonication technique using different types of lipids and surfactants. Lipid nanoparticles were characterized in terms of entrapment efficiency, particle size, Zeta potential, differential scanning calorimetry, transmission electron microscopy, and in-vitro release studies. Results The lipid nanoparticles showed mean diameters of 210–730 nm, whereas the entrapment efficiency ranged from 50 to 84% depending on emulsifier and lipid concentration or type. MLX-loaded SLNs showed spherical particles with Zeta potentials varying from −15.7 to −30.5 mV. A differential scanning calorimetry study revealed that MLX encapsulated in SLNs was in the amorphous form. All nanoparticle formulations exhibited sustained release characteristics, and the release pattern followed the Higuchi’s equation. The analysis of results revealed that the type and concentration of the emulsifier or lipid used had a significant effect on the physicochemical properties on the investigated SLNs formulations. Conclusion The present study indicates that SLNs could potentially be exploited as carrier systems for MLX, with improved drug loading capacity and controlled drug release.

Elastin-based protein polymer nanoparticles carrying drug at both corona and core suppress tumor growth in vivo

Numerous nanocarriers of small molecules depend on either non-specific physical encapsulation or direct covalent linkage. In contrast, this manuscript explores an alternative encapsulation strategy based on high-specificity avidity between a small molecule drug and its cognate protein target fused to the corona of protein polymer nanoparticles. With the new strategy, the drug associates tightly to the carrier and releases slowly, which may decrease toxicity and promote tumor accumulation via the enhanced permeability and retention effect. To test this hypothesis, the drug Rapamycin (Rapa) was selected for its potent anti-proliferative properties, which give it immunosuppressant and anti-tumor activity. Despite its potency, Rapa has low solubility, low oral bioavailability, and rapid systemic clearance, which make it an excellent candidate for nanoparticulate drug delivery. To explore this approach, genetically engineered diblock copolymers were constructed from elastin-like polypeptides (ELPs) that assemble small (<100nm) nanoparticles. ELPs are protein polymers of the sequence (Val-Pro-Gly-Xaa-Gly)n, where the identity of Xaa and n determine their assembly properties. Initially, a screening assay for model drug encapsulation in ELP nanoparticles was developed, which showed that Rose Bengal and Rapa have high non-specific encapsulation in the core of ELP nanoparticles with a sequence where Xaa=Ile or Phe. While excellent at entrapping these drugs, their release was relatively fast (2.2h half-life) compared to their intended mean residence time in the human body. Having determined that Rapa can be non-specifically entrapped in the core of ELP nanoparticles, FK506 binding protein 12 (FKBP), which is the cognate protein target of Rapa, was genetically fused to the surface of these nanoparticles (FSI) to enhance their avidity towards Rapa. The fusion of FKBP to these nanoparticles slowed the terminal half-life of drug release to 57.8h. To determine if this class of drug carriers has potential applications in vivo, FSI/Rapa was administered to mice carrying a human breast cancer model (MDA-MB-468). Compared to free drug, FSI encapsulation significantly decreased gross toxicity and enhanced the anti-cancer activity. In conclusion, protein polymer nanoparticles decorated with the cognate receptor of a high potency, low solubility drug (Rapa) efficiently improved drug loading capacity and its release. This approach has applications to the delivery of Rapa and its analogs; furthermore, this strategy has broader applications in the encapsulation, targeting, and release of other potent small molecules.

Formulation and Characterization of Nanostructured Lipid Carrier of Ubiquinone (Coenzyme Q10)

Nanostructured lipid carriers (NLC) developed from mixtures of solid lipid and spatially incompatible liquid lipid by solvent diffusion method. This new type of lipid nanoparticles offers the advantage of improved drug loading capacity and release properties. In this study, Glyceryl distearate and Glyceryl behenate were chosen as solid lipid and Glyceryl triacetate used as liquid lipid. Ubidecarenone used as model drug was incorporated into the NLC. The influences of different type of solid lipid and liquid lipid concentration on physiochemical properties of the NLC were characterized. As a result, the drug encapsulation efficiencies were improved by adding the liquid lipid into the solid lipid of nanoparticles. NLC had higher encapsulation efficiency and drug release. In addition, in vivo study showed that the antioxidant activity of the Ubidecarenone (Co. Q10 NLC) was more effective than the Ubidecarenone (Coenzyme Q10) solution form on DPPH scavenging, anti-lipid peroxidation, lowers the effect of amnesia induced by scopolamine and increased bioavailability observed in Cmax, Tmax, and AUC. These results indicated that nanostructured lipid formulation of Ubiquinone (Coenzyme Q10) has more antioxidant activity than that of solution form and it can be used to reduce the oxidative stress and to increase the antioxidant enzyme activity in many neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease etc.

Ethylene glycol oligomer modified-sodium alginate for efficiently improving the drug loading and the tumor therapeutic effect.

The high viscosity of sodium alginate (ALG) causes its insufficient drug loading and limits its application as a drug carrier. In the present work, we synthesized poly(ethylene glycol) oligomer (mOEG)-modified sodium alginate (ALG-mOEG) and characterized its properties as a drug delivery system. Our results showed that ALG-mOEG displayed a greatly reduced viscosity (0.024 Pa s at 2.0 wt%) with a significantly improved drug loading capacity (18.0% (w/w)) compared with unmodified ALG (6.9% (w/w)). In addition, DOX-ALG-mOEG nanoparticles (DOX-ALG-mOEG NPs) with high drug loading were more cytotoxic for HepG2 cells in vitro and showed a higher antitumor activity in vivo compared with the control group (DOX-ALG NPs) at the same dose of DOX. DOX-ALG-mOEG NPs inhibited HepG2 proliferation in vitro with an IC50 value of 220.0 ng mL-1 and reduced tumor growth in vivo by 75.6%, while DOX-ALG NPs showed activities of 443.9 ng mL-1 and 62.7%, respectively. Meanwhile, we did not observe the "accelerated blood clearance (ABC)" phenomenon in these mOEG-modified ALG nanoparticles. In view of most biologic and chemical molecules used for the biological function being hydrophobic, we thought the ALG-mOEG scaffold also might serve as an efficient long-duration carrier for other hydrophobic molecules with minimal immunogenicity.

Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia

In the present work attempts have been made to prepare the nanostructured lipid carrier (NLC) gel, by using minoxidil, which is preferably used in case of Alopecia, i.e. baldness pattern as a effective drug. The nine different formulations of Minoxidil-NLC (NLC1–NLC9) were prepared using solid and liquid lipids with Cholesterol and Soya lecithin in different concentrations by the melt dispersion ultrasonication method. Properties of NLC1–NLC9 such as the particle size and its distribution, the scanning electron microscopy (SEM), the drug entrapment efficiency (EE), and the drug release behavior were investigated. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadability, rheology, and in vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies. The formulated NLC3 was spherical in shape, with average particle size of 280nm, zeta potential of −42.40mV and entrapment efficiency of 86.09%. Differential Scanning Calorimeter (DSC) measurements revealed that imperfect crystallization occurred in the inner core of the NLC particles. The drug release behavior from the NLC displayed a biphasic drug release pattern with burst release at the initial stage followed by sustained release. These results indicated that the NLC3 is a suitable carrier of minoxidil with improved drug loading capacity and controlled drug release properties. It has been observed that NLC gel produces the gel with good consistency, homogeneity, spreadability and rheological behavior. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 16h. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nanoparticulate form helped us to attain the objective of faster onset yet prolonged action as evident from in vitro release.

Preparation and characterization of silybin-loaded nanostructured lipid carriers

Nanostructured lipid carriers (NLC) are a new generation of lipid nanoparticles, which are produced by controlled mixing of solid lipids with spatially incompatible liquid lipids leading to special nanostructures with improved drug incorporation and release properties. In this study, silybin-loaded nanostructured lipid carriers with various liquid lipid content were successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature. The size and morphology of nanoparticles were significantly influenced by the liquid lipid content. As the liquid lipid content increased to 20 wt%, the obtained particles showed distinguished smaller size. Compared with solid lipid nanoparticles (SLN), NLC presented improved drug loading capacity which increased with increasing the liquid lipid content. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis indicated that the incorporation of liquid lipids could interfere with the crystallization of solid lipids. The drug in vitro release behavior from NLC displayed a biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards, and the successful controlled release rate can be achieved by controlling the liquid lipid content.

A Novel pH and Thermo-sensitive N,O-Carboxymethyl Chitosan-graft-Poly(N-isopropylacrylamide) Hydrogel for Controlled Drug Delivery

Abstract A novel kind of thermo and pH-responsive hydrogels was prepared by reacting N,O-carboxymethyl chitosan (NOCC) with amino-telechelic poly(Nisopropylacrylamide) (PNIPAAm-NH2) as a drug delivery carrier. The hydrogels were characterized by FT-IR and 1H-NMR techniques. The phase transition behavior of the hydrogels was found to be dependent on the NOCC/PNIPAAm-NH2 weight ratio and pH value of the medium. The hydrogels with a higher content of PNIPAAm showed a definite phase transition at 32 °C as it occurs in pure PNIPAAm. For the release study, NOCC-g-PNIPAAm beads were prepared using glutaraldehyde (GA) as a crosslinking agent. The swelling ratio of the beads was higher in pH 2.1 than pH 7.4. Moreover, the swelling ratio of the beads decreased with the increase in PNIPAAm content of the beads. The release profile of NOCCg- PNIPAAm beads showed a slower and controlled release of the entrapped ketoprofen, and found that the release behaviour was influenced by both the pH and temperature of the medium. It is expected that these smart hydrogels may be useful to develop drug delivery systems with improved drug loading capacity and controlled release behaviour.

Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: Nanostructured lipid carriers

Nanostructured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of colloidal drug delivery system, which offer the advantage of improved drug loading capacity and release properties. Surfactants play important roles in the formation and characterization of NLC. In order to investigate the influence of surfactants on properties of NLC, four types of surfactants and their mixtures were used in the absence of model drugs thereby avoiding the interaction between surfactants and drugs. The hot high-pressure homogenization method was employed to produce NLC and the physicochemical properties of NLC, such as particle size distribution, zeta potential and DSC analysis were investigated. The results indicated that ionic surfactants such as sodium deoxycholate (SDC), showed obviously low emulsification efficiency in the preparation. However, it increased the zeta potential of nanoparticles leading to improve the physical stability of the system. Non-ionic emulsifier, especially Poloxamer 188, offered additional steric stabilization effect avoiding aggregation of the nanoparticles in the colloidal system. The formulation in the study combined four types of additives including ionic surfactant (SDC), non-ionic emulsifier (Poloxamer 188 and Tween-80), and Lecithin to obtain favorably stable NLC drug delivery system, which could stabilize for more than 1 year without phase separation at 4 °C.