Hydrophilic Drug Loading Research Articles

Multi-thermo responsive double network composite hydrogel for 3D printing medical hydrogel mask

3D printing of multifunctional hydrogels offers great opportunities for developing innovative biomedical technologies as it can provide custom-designed shapes and structures conformal to arbitrary contours. There have been significant improvements of the 3D printing techniques, but the available printable hydrogel materials limit the progress. Here, we investigated the use of a poloxamer diacrylate (Pluronic P123) to augment the thermo-responsive network composed of poly(N-isopropylacrylamide) and develop a multi-thermoresponsive hydrogel for photopolymerization 3D printing. The hydrogel precursor resin was synthesised to be printable with high-fidelity of fine structures and once cured can form a robust thermo-responsive hydrogel. By utilizing N-isopropyl acrylamide monomer and a Pluronic P123 diacrylate crosslinker as 2 separate thermo-responsive components it was found that the final hydrogel displayed 2 distinct lower critical solution temperature (LCST) switches. This enables the loading of hydrophilic drugs at fridge temperature and improving the strength of the hydrogel at room temperature while still maintaining a drug release at body temperature. The thermo-responsive material properties of this multifunctional hydrogel material system were investigated, showing a significant promise as a medical hydrogel mask. Furthermore, it is demonstrated that it can be printed in sizes large enough to fit and adhere to a human face at 1:1 scale with high dimensional accuracy, as well as its ability to load with hydrophilic drugs.

Construction of nanohydrogels for enhanced delivery of hydrophilic and hydrophobic drugs and improving chemotherapy efficacy

As an emerging drug carrier, nanohydrogels have been widely used for drug delivery. However, the traditional nanohydrogels are commonly limited to large molecular hydrophilic drug loading due to the structure features of high water content and large pore size. Herein, a novel supramolecular recognition assisted nanohydrogel drug delivery platform was designed and constructed. As a proof-of-concept, through the supramolecular drug&cyclodextrin complexes screening strategy, the newly designed nanohydrogels possess general loading capability for a wide variety of small molecular hydrophilic and hydrophobic drugs. The results demonstrated that the supramolecular interactions endow the nanohydrogels with higher drug loading efficiency and controlled release ability. More interesting, the as prepared supramolecular recognition assisted nanohydrogel showed wrinkled surface morphology that found to contribute to the enhanced tumor cell uptake and nuclear drug delivery. Furthermore, the improving anti-tumor efficacy was demonstrated in both in vitro and in vivo models. This work broadens the construction strategy of nanohydrogels and provides a general delivery platform for efficient tumor chemotherapy.

Hydrophobic and hydrophilic drug loading capacity of micro diatom frustule from diatomite

The aim of this work was to strengthen the evidence of using micro diatom frustule as a promising candidate for drug loading materials for both hydrophobic and hydrophilic drug models. The morphological, surface elemental composition of diatomite powder, a raw source of micro diatom frustules and purified diatomite to collect micro diatom frustule were investigated. Scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS) confirmed again the porous silica structure of micro diatom structure as well as validated a necessity of raw diatomite purification before using. UV- vis was used to measure drug loading content of untreated and treated surface of micro diatom frustule with maximum loading for hydrophobic and hydrophilic drugs after 24 hours were at 5.48 ± 0.42% and 5.70 ± 0.34, respectively. Moreover, we also proved that the ability of drug adsorption on materials surface by the reduction of specific surface area and pore size of micro diatom frustule after loading using a (Brunauer–Emmett–Teller) BET method. Besides, the hydrophobic loading capacity of materials was affected by surface modification. Based on the results, micro diatom frustule showed a potential for a drug delivery system.

Photodynamic Bubble-Generating Microneedles for Enhanced Transdermal Cancer Therapy

Active bubble-generating microneedles (MNs) upon skin interstitial fluid (ISF) contact facilitate deeper and more efficient delivery of intradermal therapeutics. However, bubble-generating MN platforms are sensitive to moisture, which limits their variety to load various functional drugs. This article presents a frozen immersion method that facilitates both hydrophobic and hydrophilic drug loading onto bubble-generating MNs without compromising both drug and MN properties. The formed bubbles upon ISF contact induce distinct vortex flow that produces a propulsion force to enhance drug transportation. The efficiency of transdermal drug delivery is further enhanced by sonophoresis. The drug delivery efficiency of this platform is first evaluated ex vivo using fresh mouse skins and human keloid tissues. Later, in the tumor-bearing mouse model, the platform enhances the skin penetration of photosensitizers (i.e., methylene blue) and correspondingly improves the efficacy of photodynamic therapy.

Study on the protection of dextran on erythrocytes during drug loading

In comparison to other carriers, erythrocytes (red blood cells, RBCs) hold the advantages of unmatched long circulation, biocompatibility and biodegradability. However, because of the defects in RBCs carriers caused by the drug loading process, the biological activities of drug-loaded RBCs are worse than those of natural RBCs (NRBCs). We aim to study the protective effect of dextran on the activity of drug-loaded RBCs. Different molecular weights of dextran were selected and added to a hypotonic drug solution to prepare drug-loaded RBCs by the hypotonic preswelling method. Water-soluble betamethasone sodium phosphate (BSP) and fat-soluble artesunate (AS) were selected as model drugs. The results showed that the addition of dextran with a molecular weight of 40 kDa and a concentration of 10 % could significantly increase the Na+/K+-ATPase activity, improve the drug loading amount and lower the phosphatidylserine eversion rate. Moreover, it maintained a similar osmotic fragility to NRBCs and exhibited no effect on the morphological structure of drug-loaded RBCs. Laser confocal results showed tight covering of dextran over RBCs, which could explain the protective effects. The addition of dextran increased the activity of drug-loaded RBCs without affecting their in vivo circulation (at least nine days). In conclusion, 10 % dextran with a weight of 40 kDa displayed a significant protective effect on the bioactivity of drug-loaded RBCs, which could be expected to be a better way to facilitate hydrophobic and hydrophilic drug loading by RBCs.

Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

Nanoparticle drug delivery applications have predominantly focused on the entrapment and delivery of hydrophobic molecules with poor water solubility. However, benefits can also be obtained from nanoparticle-based delivery of hydrophilic therapeutics. This study reports on the development of a p(HEMA-ran-GMA)-based nanoparticle synthesized via a spontaneous water-in-oil inverse nanoemulsion to deliver doxorubicin, a water-soluble chemotherapeutic. High drug loading efficiency and sustained release of doxorubicin from Cy5-functionalized p(HEMA-ran-GMA) nanoparticles enabled effective inhibition of the MCF-7 human breast cancer derived cell line. Direct comparative analyses with a hydrophobic PGMA nanoparticle demonstrated enhanced capabilities of the p(HEMA-ran-GMA)-based nanoparticle in vitro. The results suggest that p(HEMA-ran-GMA)-based nanoparticles, which are better suited for hydrophilic drug loading and delivery, may have the potential for the improved therapeutic effect in vivo by enhanced permeation and retention of the nanoparticles by avoidance of off-site side effects of the chemotherapeutic.

Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation.

Solid lipid nanoparticle (SLN) is a promising approach for delivery of various drugs including proteins and peptides. However, the loading of hydrophilic drugs into the lipoid matrix of SLNs is challenging. The statistical design is a potential method facilitating the optimization of nanoparticles characteristics. In this study, the Box-Behnken design was conducted to optimize the preparation of Erythropoietin (EPO) loaded SLNs. Circular dichroism, size exclusion chromatography, SDS-PAGE, and ELISA tests were used to prove the compatibility of the process with the stability of EPO. In the controlled situation, EPO preserved its conformation and activity during the SLN preparation. Regarding the particle size, entrapment efficiency, and polydispersity index, an optimum formulation was obtained with 130 mg Span®80, 152.5 μl EPO, and 1.9 min high-shear homogenization. Using the optimum condition, 280 nm sized SLNs with the narrow size distribution of 0.282 and entrapment efficiency of 43.4% were acquired. The in vitro cytotoxicity of optimum SLN formulation was conducted using MTT assay to show its safety on the evaluated cell line. The in vivo studies demonstrated that 2500 U EPO loaded SLN has similar or even better effects on elevating the RBC, hemoglobin, and hematocrit level compared to the 5000 U EPO solution. Generally, this study proposed a suitable EPO-loaded SLN preparation method as a potential drug delivery system for proteins.

Poly(methyl vinyl ether-co-maleic acid) Hydrogels Containing Cyclodextrins and Tween 85 for Potential Application as Hydrophobic Drug Delivery Systems

Hydrogels have been extensively investigated as a platform for drug delivery. However, their use for the delivery of hydrophobic drugs has been limited by their incompatibility with hydrophobic drug molecules. The chemical modification of the structure of the hydrogels to include hydrophobic moieties has been proven to be a good alternative to increase the stability and solubility of hydrophobic drugs in the polymer matrix of the hydrogel. The inclusion of hydroxypropyl-β-cyclodextrins (HPBCD) and Tween® 85 (T85) within hydrogel matrices has the potential to improve hydrophobic drug loading and release. HPBCD have the ability to host hydrophobic drug molecules in their cone-like structure, forming inclusion complexes through host-guest interactions. On the other hand, T85 is an amphiphilic molecule and, consequently, has the potential to increase hydrophilic drug loading within the hydrogels. In the present work, a new type of hydrogel made from poly(methyl vinyl ether-co-maleic acid) (GAN) and poly(ethylene glycol) (PEG) containing T85 and HPBCD was synthesized for hydrophobic drug release. Hydrogels were based on GAN crosslinked (PEG) and HPBCD and/or T85 via an esterification in the solid state (solvent free). The synthesised hydrogels were characterised using Fourier transform infrared (FTIR) spectroscopy, swelling studies and contact angle measurements. The hydrogels showed swellings ranging from 140 to 180%. The inclusion of T85 in the hydrogels improved the wettability of the materials. On the other hand, the inclusion of HPBCD within the hydrogels decreased the wettability as the contact angle between the hydrogels and water increased with the HPBCD content. Finally, the materials were loaded with an ophthalmic drug, dexamethasone (DX). HPBC-containing hydrogels showed a higher DX uptake and, consequently, also a higher capacity of DX release. On the other hand, T85 containing hydrogels did not show any improvement over the hydrogels containing only GAN and PEG. The hydrogels were able to provide sustained DX release over periods of 6 h.

Comparing Strategies for Magnetic Functionalization of Microbubbles.

The advancement of ultrasound-mediated therapy has stimulated the development of drug-loaded microbubble agents that can be targeted to a region of interest through an applied magnetic field prior to ultrasound activation. However, the need to incorporate therapeutic molecules while optimizing the responsiveness to both magnetic and acoustic fields and maintaining adequate stability poses a considerable challenge for microbubble synthesis. The aim of this study was to evaluate three different methods for incorporating iron oxide nanoparticles (IONPs) into phospholipid-coated microbubbles using (1) hydrophobic IONPs within an oil layer below the microbubble shell, (2) phospholipid-stabilized IONPs within the shell, or (3) hydrophilic IONPs noncovalently bound to the surface of the microbubble. All microbubbles exhibited similar acoustic response at both 1 and 7 MHz. The half-life of the microbubbles was more than doubled by the addition of IONPs by using both surface and phospholipid-mediated loading methods, provided the lipid used to coat the IONPs was the same as that constituting the microbubble shell. The highest loading of IONPs per microbubble was also achieved with the surface loading method, and these microbubbles were the most responsive to an applied magnetic field, showing a 3-fold increase in the number of retained microbubbles compared to other groups. For the purpose of drug delivery, surface loading of IONPs could restrict the attachment of hydrophilic drugs to the microbubble shell, but hydrophobic drugs could still be incorporated. In contrast, although the incorporation of phospholipid IONPs produced more weakly magnetic microbubbles, it would not interfere with hydrophilic drug loading on the surface of the microbubble.

Intrinsic Ultrahigh Drug/miRNA Loading Capacity of Biodegradable Bioactive Glass Nanoparticles toward Highly Efficient Pharmaceutical Delivery.

The lack of safe and efficient drug and gene delivery vectors has become a major obstacle for the clinical applications of drug and nonviral gene therapy. To date, for nonviral gene vectors, most studies are focused on cationic polymers, liposomes, and modified inorganic nanoparticles which have shown high cellular toxicity, low transfection efficiency, or nondegradation. Additionally, few biodegradable biomaterials demonstrate intrinsic high binding abilities to both drug and gene. Bioactive glasses (BGs) have achieved successful applications in bone regeneration due to their high biocompatibility and biodegradation. Here, for the first time, we demonstrate the intrinsic ultrahigh drug and miRNA binding ability of bioactive glass nanoparticles (BGNs) without any cationic polymer modification. BGNs demonstrate an over 45-fold improvement in hydrophilic drug loading (diclofenac sodium) and 7-fold enhancement in miRNA binding over their corresponding silica nanoparticles. The hydrophilic drug loading ability of BGNs (>45 wt % loading) is also higher than that of most other reported inorganic nanoparticles, including mesoporous silica nanoparticles. BGNs show significantly lower cytotoxicity and higher cellular uptake and miRNA transfection efficiency compared to those of commercial transfection reagents polyethylenimine and lipofectamine 3000. Our results demonstrate that BGNs may become a new competitive vehicle for drug and gene delivery applications. This study may also provide a new strategy to develop novel biomaterials with intrinsic drug and gene binding ability for disease therapy.

Supercritical CO2 assisted liposomes formation: Optimization of the lipidic layer for an efficient hydrophilic drug loading

Liposomes are natural vesicles generally based on phosphatidylcholine (PC). The optimization of the lipid bilayer composition with the addition of little percentages of natural lipids is still at early stage due to the difficulties experienced by classical liposome formation processes, mainly, in reproducibility and encapsulation efficiency.Supercritical assisted liposome formation (SuperLip) has demonstrated that these limitations can be overcome. Therefore, in this work, this process has been tested to produce liposomes of controlled nanometric diameter and the effect of water solution flow rate on drug encapsulation efficiency was investigated. The addition of cholesterol (Chol) or phosphatidylethanolamine (PE) was also studied to gain the control on the release rate of the drug entrapped in liposomes. Theophylline was selected as the model hydrophilic drug.Using SuperLip process, PC/Chol and PC/PE liposomes were successfully produced with nanometric mean diameters down to 200nm. Optimization of both lipid composition and SuperLip operative parameters allowed to obtain theophylline encapsulation efficiencies up to 98%. Drug release kinetics were affected by liposome composition, in particular, the addiction of Chol and PE allowed to slow down theophylline release rate. These results confirmed the possibility of producing liposomes with a complex architecture of the lipid membrane using the SuperLip process.

A reformative shear precipitation procedure for the fabrication of vancomycin-loaded poly(lactide-co-glycolide) microspheres.

This study reports the encapsulation of vancomycin, as a model hydrophilic drug, into poly(lactide-co-glycolide) microspheres using a novel reformative shear precipitation procedure. In contrast to the external aqueous phase used in the conventional microencapsulation technique based on emulsion solvent evaporation/extraction, the reformative shear precipitation procedure explored in this study uses a shear medium composed of glycerol as the viscous medium and ethanol as polymer antisolvent, which is relatively immiscible with the hydrophilic drug. This limits drug diffusion and leads to rapid microsphere solidification, which allows a large proportion of the hydrophilic drug to be encapsulated within the microspheres. The influence of various processing parameters, including polymer concentration, volume ratio of ethanol to glycerol in the shear medium, volume of aqueous drug solution, initial drug loading, and injecting rate of the drug-polymer emulsion, on the encapsulation efficiency and characteristics of resulting microspheres were investigated. The morphology and release characteristics, as well as mechanical, invitro and invivo behaviour of vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using the novel procedure were also investigated. The results demonstrated that the reformative shear precipitation procedure could achieve the loading of hydrophilic drugs into poly(lactide-co-glycolide) microspheres with high encapsulation efficiency, and the success of the procedure was largely influenced by the volume ratio of ethanol to glycerol in the shear medium. Vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using this procedure demonstrated favourable mechanical characteristics, antibacterial activity, and invivo degradation behaviour which suggested their suitability for use as a sustained delivery system.

Control of Alginate Core Size in Alginate-Poly (Lactic-Co-Glycolic) Acid Microparticles.

Core-shell alginate-poly (lactic-co-glycolic) acid (PLGA) microparticles are potential candidates to improve hydrophilic drug loading while facilitating controlled release. This report studies the influence of the alginate core size on the drug release profile of alginate-PLGA microparticles and its size. Microparticles are synthesized through double-emulsion fabrication via a concurrent ionotropic gelation and solvent extraction. The size of alginate core ranges from approximately 10, 50, to 100 μm when the emulsification method at the first step is homogenization, vortexing, or magnetic stirring, respectively. The second step emulsification for all three conditions is performed with magnetic stirring. Interestingly, although the alginate core has different sizes, alginate-PLGA microparticle diameter does not change. However, drug release profiles are dramatically different for microparticles comprising different-sized alginate cores. Specifically, taking calcein as a model drug, microparticles containing the smallest alginate core (10 μm) show the slowest release over a period of 26 days with burst release less than 1 %.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-015-1222-7) contains supplementary material, which is available to authorized users.

Preparation and Microbiological Evaluation of Amphiphilic Kanamycin-Lipoamino Acid Ion-Pairs.

Amphiphilic ion-pairs of kanamycin (KAN) were prepared by evaporation of a water-ethanol co-solution of KAN base and a lipoamino acid bearing a 12-carbon atoms alkyl side chain (LAA12), at different molar ratios. Infrared spectroscopy confirmed the structure of ion-pairs, while differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) studies supported the formation of new saline species with a different crystalline structure than the starting components. The solubility pattern shown in a range of both aqueous and organic solvents confirmed that the ion-pairs possess an amphiphilic character. The LAA12 counter-ion showed not to improve the antibacterial activity of KAN, suggesting that such chemical strategy is not able to favor the penetration of this drug inside the bacteria cells. Nevertheless, a slight improving, i.e., a one-fold dilution, was observed in E. coli. The present study can also serve as the basis for a further evaluation of LAA ion-pairing of antibiotics, as a means to improve the loading of hydrophilic drugs into lipid-based nanocarriers.

The effect of inorganic salt type and concentration on hydrophilic drug loading into microspheres using the emulsion/solvent diffusion method

Aim: In order to avoid gastric irritation caused by tolmetin sodium (TS), gastro resistant Eudragit® S 100 microsphere formulations were prepared with the emulsion/solvent diffusion method.Materials: Considering the high water solubility of the TS molecule, the effects of the presence of inorganic salt (NaCl, NaBr and KH2PO4; 0.1 M and 1.0 M) in external phase and external phase pH on the encapsulation efficiency were evaluated.Results: Percentage yield value was found to vary between 55.8% and 72.1%. Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl, NaBr and KH2PO4. The microspheres were observed to have a spherical shape and the measured particle size values varied between 52.1 and 81.5 µm. The released amounts of the drug were found to be low as the inorganic salt concentrations increased.Conclusion: Conclusively, drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit® S 100 polymer, and these formulations are considered to be a model for other orally administered drugs with similar problems.

One-step fabrication of core-shell structured alginate-PLGA/PLLA microparticles as a novel drug delivery system for water soluble drugs.

Current focus on particulate drug delivery entails the need for increased drug loading and sustained release of water soluble drugs. Commonly studied biodegradable polyesters, such as poly(lactide-co-glycolide) (PLGA) and poly(l-lactide) (PLLA), are lacking in terms of loading efficiency of these drugs and a stable encapsulation environment for proteins. While hydrogels could enable higher loading of hydrophilic drugs, they are limited in terms of controlled and sustained release. With this in mind, the aim was to develop microparticles with a hydrophilic drug-loaded hydrogel core encapsulated within a biodegradable polyester shell that can improve hydrophilic drug loading, while providing controlled and sustained release. Herein, we report a single step method of fabricating microparticles via a concurrent ionotropic gelation and solvent extraction. Microparticles fabricated possess a core-shell structure of alginate, encapsulated in a shell constructed of either PLGA or PLLA. The cross-sectional morphology of particles was evaluated via scanning electron microscopy, calcium alginate core dissolution, FT-IR microscopy and Raman mapping. The incorporation of alginate within PLGA or PLLA was shown to increase encapsulation efficiency of a model hydrophilic drug metoclopramide HCl (MCA). The findings showed that the shell served as a membrane in controlling the release of drugs. Such gel-core hydrophobic-shell microparticles thus allow for improved loading and release of water soluble drugs.

Lyophilization of cholesterol-free PEGylated liposomes and its impact on drug loading by passive equilibration

The obstacles in translating liposome formulations into marketable products could be attributed to their physical instabilities upon long-term storage as aqueous dispersions. Lyophilization is the most commonly used technique to improve physical stability of liposomes. The development of stable, lyophilized liposomes is focused primarily on the cholesterol-containing liposomes or pure phosphatidylcholine-based liposomes, with minimal studies on cholesterol-free, pegylated (CF-PEG) liposomes which have emerged as an important class of liposome drug carriers. Hence, it is our interest to investigate the effect of lyophilization on CF-PEG liposomes, and specifically, on drug loading via the passive equilibration method. Three different sugar cryoprotectants were used at two different sugar-to-lipid molar ratios (S/L). Our results demonstrated that CF-PEG liposomes lyophilized with sucrose at S/L=5:1 yielded the best cryoprotective effect, as characterized by size, polydispersity indices, and microscopic examination upon liposome reconstitution. The lyophilized liposomes had low water content of 2.59±0.18%. Of note, lyophilized CF-PEG liposomes exhibited two-fold increase in drug content when carboplatin was loaded via the passive equilibration method, and the in vitro drug release profile of these liposomes were not different from that of the non-lyophilized counterparts. Taken together, we envisioned that a stable, lyophilized empty CF-PEG liposome system could be coupled to hydrophilic drug loading via the passive equilibration method to produce a liposomal drug kit product.

Characterization and drug release behavior of highly responsive chip-like electrically modulated reduced graphene oxide–poly(vinyl alcohol) membranes

Hybrid hydrogel membranes composed of reduced graphene oxide (rGO) nanosheets and a poly (vinyl alcohol) (PVA) matrix were investigated as an electrically responsive drug release system. The rGO nanosheets in the matrix act as a physical barrier to inhibit the release of the model anesthetic drug, lidocaine hydrochloride, but the highly responsive release can be enhanced by the presence of rGO when exposed to an electrical stimulus. More interestingly, the on-demand drug release profiles of the assembled rGO–PVA hydrogel into a chip-like device can be highly controlled by an external electrical field. Release profiles ranging from a slow-elution pattern to a rapid release under electrical field treatment can be achieved by manipulating the rGO–PVA composition. Moreover, under cyclic exposure to an electrical stimulus, a highly controllable and repeatedly pulsatile release with desirable precision is obtained from the rGO–PVA hydrogel, implying that the hydrogel exhibits excellent anti-fatigue properties. By combining with the enhanced structural integrity and biocompatibility, the electrically responsive rGO–PVA hydrogel has demonstrated potential biological applications in drug delivery systems. In addition, the easy loading of hydrophilic drugs into the rGO–PVA hydrogel opens up a promising future in biological applications, such as transdermal therapy and wound healing.

Enhancement of hydrophilic drug loading and release characteristics through micellization with new carboxymethyldextran-PEG block copolymers of tunable charge density

The micellization of a model cationic drug, diminazene diaceturate (DIM) and a series of new diblock copolymers, carboxymethyldextran-poly(ethylene glycols) (CMD-PEG), were evaluated as a function of the ionic charge density or degree of substitution (DS) of the carboxymethyldextran block and the molar ratio, [+]/[−], of positive charges provided by the drug to negative charges provided by CMD-PEG. Micelles ([+]/[−] = 2) incorporated up to 64% (w/w) DIM and ranged in hydrodynamic radius ( R H) from 36 to 50 nm, depending on the molecular weight and DS of CMD-PEG. The critical association concentration (CAC) was on the order of 15–50 mg/L for CMD-PEG of DS > 60%, and ca. 100 mg/L for CMD-PEG of DS ∼ 30%. The micelles were stable upon storage in solution for up to 2 months and after freeze-drying in the presence of trehalose. They remained intact within the 4 < pH < 11 range and for solutions of pH 5.3, they resisted increases in salinity up to ∼0.4 M NaCl in the case of CMD-PEG of high DS. However, micelles of DIM and a CMD-PEG of low DS (30%) disintegrated in solutions containing more than 0.1 M NaCl, setting a minimum value to the DS of copolymers useful in in vivo applications. Sustained in vitro DIM release was observed for micelles of CMD-PEG of high DS ([+]/[−] = 2).

현탁된 고형지질나노입자 내로 친수성 약물의 봉입률을 증대시키기 위한 w/o/w 에멀션 가온용융유화법의 평가

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel, cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.