Modification of hydrophilic polymer network to design a carrier for a poorly water-soluble substance

pH sensitive, nontoxic, and biocompatible poly(methacrylic) acid (PMAA) based soft networks have been extensively used in the design of systems for targeted drug delivery. Still, their highly hydrophilic nature limits their potential to be used as a carrier of poorly water-soluble substances. With the aim to overcome this limitation, the present study details a new approach for modification of PMAA based carriers using two amphiphilic components: casein and liposomes. The FTIR analysis revealed structural features of each component as well as the synergetic effect that originated from the formation of specific interactions. Namely, hydrophobic interactions between the poorly water-soluble model drug (caffeine) and casein enabled caffeine encapsulation and controlled release, while addition of liposomes ensured better control of the release rate. The morphological properties of the carriers, swelling behavior, and release kinetics of caffeine were investigated depending on the variable synthesis parameters (neutralization degree of methacrylic acid, concentration of caffeine, presence/absence of liposomes) in two different media simulating the pH environment of human intestines and stomach. The data obtained from in vitro caffeine release were correlated and analyzed in detail using several mathematical models, indicating significant potential of investigated carriers for targeted delivery and controlled release of poorly water-soluble substances.     

Retention of Eucalyptol,a Natural Volatile Insecticide,in Delivery Systems Based on Hydroxypropyl‐β‐Cyclodextrin and Liposomes

Eucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention. Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release.     

Production of new hybrid systems for drug delivery by PGSS (Particles from Gas Saturated Solutions) process

The formulation of S-(+)-ibuprofen as a model water-insoluble drug in different carrier materials (poloxamers, gelucire and glyceryl monostearate, GMS) by Particles from Gas Saturated Solutions (PGSS) technique has been studied. Porous, spherical particles of 50⿿200 μm have been obtained with encapsulation efficiencies up to 90%. Differential scanning calorimetry assays reveal modifications on the structure of the material, with formation of a solid solution in experiments with poloxamer carriers, and formation of solid dispersions with a possible reduction of the crystallinity of the carrier in experiments with GMS. Drug release tests in simulated gastric and intestinal fluids have been performed. Formulations with poloxamer carrier materials provided an increased solubility of ibuprofen in the gastrointestinal fluids, with a very fast release and dissolution of this compound, while gelucire and GMS carriers did not improve the solubility of ibuprofen, but provided a slower, controlled release of the drug. PGSS-processed samples presented a superior performance over physical mixtures in terms of the solubility increase and the control of the release rate. These results show the wide possibilities and flexibility of the PGSS technique for the development of hybrid formulations of water-insoluble active compounds with hydrophilic or hydrophobic carrier materials, achieving either an increased, accelerated dissolution, or a slower, controlled delivery, depending on the choice of carrier materials.     

Shikonin‐loaded liposomes as a new drug delivery system: Physicochemical characterization and in vitro cytotoxicity

Alkannin and shikonin are naturally occurring hydroxynaphthoquinones with a well‐established spectrum of wound healing, antimicrobial, anti‐inflammatory, and antioxidant activities. Recently, extensive scientific effort has been focused on their effectiveness on several tumors and mechanism(s) of antitumor activity. Liposomes have been proved as adequate drug carriers offering significant advantages over conventional formulations, such as controlled release and targeted drug delivery, leading to the appearance of several liposomal formulations in the market, some of them concerning anticancer drugs. The aim of the present study was to prepare shikonin‐loaded liposomes for the first time in order to enhance shikonin therapeutic index. An optimized technique based on the thin film hydration method was developed and liposomes characterization was performed in terms of their physicochemical characteristics, drug entrapment efficiency, and release profile. Results indicated the successful incorporation of shikonin into liposomes, using both 1,2‐dipalmitoylphosphatidylcholine and egg phosphatidylcholine lipids. Liposomes presented good physicochemical characteristics, high entrapment efficiency and satisfactory in vitro release profile. In vitro cytotoxicity of liposomes was additionally tested against three human cancer cell lines (breast, glioma, and non‐small cell lung cancer) showing a moderate growth inhibitory activity. Practical applications: Shikonin is a naturally occurring hydroxynaphthoquinone and extensive scientific research (in vitro, in vivo, and clinical trials) has been conducted during the last years, focusing on its effectiveness on several tumors and mechanism(s) of antitumor action. The purpose of this work was to prepare and characterize shikonin‐loaded liposomes as a new drug delivery system for shikonin. Liposomal formulations provide significant advantages over conventional dosage forms, such as controlled release and targeted drug delivery for anticancer agents. Thus, liposomes could reduce shikonin's side effects, enhance selectivity to cancer cells and protect shikonin from internal biotransformations and instability matters (oxidization and polymerization). Furthermore, liposomal delivery helps overcome the low aqueous solubility of shikonin, which is the major barrier to its oral and internal administration, since it cannot be dissolved and further absorbed from the receptor.     

Functionalized chitosan with super paramagnetic hybrid nanocarrier for targeted drug delivery of curcumin

Recently, hydrophobically functionalized polymers have been deployed as carriers to improve the encapsulation of hydrophobic drugs. The metal nanocomposites are extensively used to improve the biocompatibility of the formulation and target the drug to the specialized site. In our current study, naphthalene acetate (NAA) was incorporated into the amine group of chitosan to form a hydrophobically functionalized chitosan–NAA drug delivery carrier. The calcium ferrite nanoparticles (CFNP) were embedded in the chitosan–NAA matrix to form a super paramagnetic hybrid nanocarrier for controlled curcumin drug delivery. Various analytical techniques were performed to ensure the functional group modifications, thermal stability, surface nature and morphological behavior of synthesized hybrid carriers. The maximum encapsulation efficiency of 93.6% was obtained under the optimized conditions of drug to chitosan–NAA at 0.1, CFNP to chitosan–NAA at 0.75 and TPP to chitosan–NAA at 1.0 (w/w) ratios, respectively, by adapting Taguchi method. Drug release studies were conducted to determine the effect of pH, drug loading concentrations and magnetic field responses. The drug release data were fitted to various kinetic release models to understand the drug release mechanism. The biocompatibility of the hybrid material was tested using L929 mouse fibroblast cells. The cytotoxicity test against breast cancer cells (MCF-7) was also performed to study the anticancer property of the hybrid paramagnetic material. The prepared curcumin-loaded chitosan–NAA/CFNP was very active against cancer cells in comparison to the normal cells. The results confirmed the applicability of the hybrid nanocarriers in cancer cell-targeted drug delivery.     

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.     

Rational design and synthesis of upconversion luminescence-based optomagnetic multifunctional nanorattles for drug delivery

Optomagnetic multifunctional composite based on upconversion luminescence nanomaterial is regarded as a promising strategy for bioimaging,disease diagnosis and targeted delivery of drugs.To explore a mesoporous nanostructure with excellent water dispersibility and high drug-loading capacity,a novel nanorattle-structured Fe3O4@SiO2@NaYF4∶Yb,Er magnetic upconversion nanorattle (MUCNR) was suc-cessfully designed by using Fe3O4 as core and NaYF4∶Yb,Er nanocrystals as shell.The microstructures and crystal phase of the as-prepared MUCNRs were evaluated by transmission electron microscopy,X-ray powder diffraction and N2 adsorption/desorption isotherms.The Kirkendall effect was adapted to explain the formation mechanism of the MUCNRs.The loading content and encapsulation efficiency of doxorubicin hydrochloride (DOX) could reach as high as 18.2％ and 60.7％,respectively.Moreover,the DOX loading MUCNR (DOX-MUCNR) system showed excellent sustained drug release and strong pH-dependent performance,which was conducive to drug release at the slightly acidic microenvironment of tumor.Microcalorimetry was used to quantify the interactions between the carrier structure and drug release rate directly.The heat release rates in the heat-flow diagrams are basically consistent with the DOX release rate,thereby showing that microcalorimetry assay not only provides a unique thermody-namic explanation for the structure-activity relationship of Fe3O4@SiO2@NaYF4∶Yb,Er MUCNRs but also provides powerful guidance to avoid the blind selection or design of drug carriers.Therefore,our work firmly provided a comprehensive perspective for using Fe3O4@SiO2@NaYF4∶Yb,Er MUCNRs as a remark-able magnetic targeted drug carrier.     

Review of Nanobiopolymers for Controlled Drug Delivery

Biodegradable polymeric nanoparticles have attracted attention as potential drug delivery devices due to its bioavailability, biocompatibility, encapsulation, controlled drug release and in drug targeting to organs/tissues, as carriers of DNA in gene therapy, deliver proteins, peptides and genes. Controlled release systems increases therapeutic activity reducing the number of drug administration. This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticulate systems including poly (lactic-co-glycolic acid), polylactic acid, chitosan, gelatin, poly hydroxy alkaonates, poly caprolactone and poly alkyl cyanoacrylate used as drug delivery system, their synthesis, encapsulation process and drug release mechanisms.     

pH and magnetic field responsive protein-inorganic nanohybrid conjugated with biotin: A biocompatible carrier system targeting lung cancer cells

Multi-stimuli responsive carrier systems, specifically targeting tumor cells are of high significance to improve the efficacy of cancer chemotherapy. In the present study, we have developed, characterized, and biologically evaluated magnetic casein-calcium ferrite hybrid biopolymeric carrier conjugated with biotin for targeted delivery of cinnamaldehyde to lung carcinoma. The dual stimuli-responsive carrier was successfully synthesized with small size, good stability, and high drug encapsulation efficiency. Natural drug cinnamaldehyde was encapsulated in the hybrid carrier, on which biotin was conjugated to facilitate selective cellular uptake. The prepared drug-carrier system exhibited pH-responsive drug release behavior with a higher release rate under acidic conditions, which can be effectively applied in targeted cancer chemotherapy. The superparamagnetic nature of calcium ferrite enabled magnetically-modulated drug delivery with faster drug release, reaching 85.5% within 4 h, in response to magnetic field stimulus. Kinetic modeling of drug release projected the diffusion-controlled release mechanism. Cell viability assay performed on L929 fibroblast and A549 lung cancer cells verified the biocompatibility and cytotoxicity of the developed formulation, respectively. The nanohybrid carrier significantly increased the anticancer potential of cinnamaldehyde with an 18-fold reduction in the IC₅₀ value, signifying the biotin-functionalized protein-inorganic nanohybrid as an efficient multifunctional platform for targeted drug delivery.     

The pH-Dependent Controlled Release of Encapsulated Vitamin B1 from Liposomal Nanocarrier

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B₁)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B₁ on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B₁ system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B₁ under physiological conditions and in artificial gastric juice, respectively.     

Preparation of microspheres with microballoons inside for floating drug‐delivery systems

The use of floating drug‐delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple‐unit, floating drug‐delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water‐in‐oil method. With theophylline as the model drug, four formulations (FI–FIV) with different ratios of the two polymers were prepared. The size distribution, drug‐encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug‐encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug‐release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near‐zero‐order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 197–202, 2004     

刺激响应性聚合物纳米胶束在药物控释中的应用研究

聚合物纳米胶束不仅可以提高药物的溶解度、生物利用度,延长药物在人体内的循环时间,还可以有效控制药物的释放而实现靶向治疗效果,极大地减少药物对人体的副作用。通过嵌段共聚物的纳米工程,可制备出具有细胞或组织靶向性且对物理或化学刺激敏感的高分子药物载体。本文综述了对pH值、温度、超声波和光具有响应性的聚合物纳米胶束的制备及其在药物控制释放领域的应用。     

DNA Nanobarrel-Based Drug Delivery for Paclitaxel and Doxorubicin

Co-delivery of anticancer drugs and target agents by endogenous materials is an inevitable approach towards targeted and synergistic therapy. Employing DNA base pair complementarities, DNA nanotechnology exploits a unique nanostructuring method and has demonstrated its capacity for nanoscale positioning and templated assembly. Moreover, the water solubility, biocompatibility, and modifiability render DNA structure suitable candidate for drug delivery applications. We here report single-stranded DNA tail conjugated antitumor drug paclitaxel (PTX), and the co-delivery of PTX, doxorubicin and targeting agent mucin 1 (MUC-1) aptamer on a DNA nanobarrel carrier. We investigated the effect of tail lengths on drug release efficiencies and dual drug codelivery-enabled cytotoxicity. Owing to the rapidly developing field of structural DNA nanotechnology, functional DNA-based drug delivery is promising to achieve clinical therapeutic applications.     

A novel one-step microemulsion method for preparation of quercetin encapsulated poly(methyl methacrylate) nanoparticles

A series of drug-loaded poly(methyl methacrylate) (PMMA) nanoparticles were prepared and studied as controlled release carrier of quercetin drug using a simple one-step differential microemulsion method. The polymer carriers were prepared in different monomer/surfactant ratios. The encapsulated PMMA nanoparticles were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and transmission electron microscopy analysis. The particle size was obtained below 10 nm with spherical shape and narrow size distribution. In vitro drug release studies were performed using a dissolution medium such as sodium phosphate buffer saline simulating body fluids. Based on a full factorial 3² experimental design, nine formulations for quercetin-loaded PMMA nanoparticles were prepared and the molar ratio of monomer/surfactant and amount of initiator were considered as independent variables, while the encapsulation efficiency, solid content and drug release were taken into account as responses. Based on ANOVA analysis, with desirability factor of 0.952, the software F3 was suggested as an optimized formulation. This formulation was composed using a monomer/surfactant molar ratio of 3 and initiator amount of 0.02 g as independent variables, while the amounts of 71.10, 25.34, and 61.54%, in the order given, for encapsulation efficiency, solid content and drug release, were obtained as responses. To estimate release mechanism, the obtained cumulative release data were fitted to zero-order, first-order, Higuchi and Korsmeyer-Peppas kinetic models. In vitro release experiments in all cases revealed that the controlled release behavior followed from Korsmeyer-Peppas kinetic model exhibited non-Fickian diffusion mechanism. Consequently, this research offers useful pharmaceutical carriers with the purpose of providing prolonged release for targeting delivery.     

Nanostructured Lipid Carriers in Alginate Microgels for the Delivery of Astaxanthin

This study aims to enhance the stability and bioavailability of astaxanthin by loading it into nanostructured lipid carriers (NLCs), then incorporating the NLCs into alginate microgels. The NLCs (about 200 nm particle size) and alginate microgels (about 1 mm particle size) are prepared using high-pressure homogenization and injection-gelation methods, respectively. Based on in vitro dissolution assessments, the astaxanthin in alginate microgels dissolves more slowly than that in NLCs. In simulated gastric digestive juice, minimal dissolution of microgel-embedded astaxanthin is detected; however, in simulated intestinal digestive juice, the dissolution is appreciably accelerated. Moreover, the 2 h bio-accessibility of astaxanthin in microgels is less than that in NLCs. At higher concentrations of sodium alginate and calcium ions, the internal pores of the microgels become smaller, resulting in slower dissolution and lower bio-accessibility of astaxanthin. As for the chemical stability of the pigment, it is improved by the secondary coating effect of hydrogelation. Hence, NLC incorporation into alginate microgels constitutes a promising strategy for the encapsulation of astaxanthin in the food industry. Practical applications : Nanostructured lipid carriers (NLCs) incorporated in alginate microgels can increase the water solubility of astaxanthin, improve its chemical stability, increase its bioavailability, and allow for its controlled release. The high-pressure homogenization method used to prepare NLCs can be easily applied on an industrial level. Moreover, the operation conditions of the injection-gelation process needed to synthesize the alginate microgels are mild, nontoxic, and nonpolluting. The NLC-alginate microgels can be used in yogurt, ice cream, and other foods.     

Effects of the process parameters on the initial burst release of poly(lactide‐co‐glycolide) microspheres containing bovine serum albumin by the double‐emulsion solvent evaporation/extraction method

The effects of fabrication parameters on the morphology, drug loading, and initial burst release of poly(lactide‐co‐glycolide) microspheres loaded with bovine serum albumin were investigated to establish an optimal process and system for the in vivo delivery of therapeutic proteins. Through the addition of salts or sugars to induce an osmotic pressure in the external water phase, large microspheres were seen to have their morphology, drug loading, and initial burst release significantly affected. However, the effect was not observed for compact microspheres less than 10 μm in diameter. The presence of poly(vinyl alcohol), Pluronic F127, and Tween 80 in the internal water phase had detrimental effects on the drug loading because of the depressed stability of the primary emulsion and competitive interactions of surface‐active substances with the polymer. However, the simultaneous addition of salts to the external water phase resulted in enhanced drug loading and decreased initial burst. The polymer concentration and volume of the internal water phase were important factors influencing the characteristics of the microspheres. These parameters were optimized for achieving the maximal drug loading and a low initial burst. The solvent extraction method yielded microspheres with a higher drug loading and a lower initial burst in comparison with the solvent evaporation method. Different ranges of protein encapsulation efficiencies were obtained with blends of poly(lactide‐co‐glycolide) and poly(ethylene glycol), depending on the molecular weight and content of poly(ethylene glycol). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Carbohydrate – lipid conjugates for targeted drug and gene delivery

The role of macrophages in the uptake and processing of liposomes evident from the increased deposition of liposomal content in cells. It has been reported that macrophages may serve as a secondary drug carrier for the delivery of liposomal drugs. The uptake of liposomal content by macrophages can be promoted by incorporation of ligands capable of interacting with macrophage surface receptors. Therefore, carbohydrate‐based molecules for targeted drug and gene delivery must be developed for rational therapy. In this article, we report the synthesis of glycolipid conjugates for applications in liposomal drug delivery systems and for targeting drugs and genes to receptors.     

Microencapsulation of caffeic acid and its release using a w/o/w double emulsion method: Assessment of formulation parameters

Caffeic acid (CAF)has numerous health benefits mainly due to its antioxidant, antibacterial and fungicide properties. However, its incorporation in skin care products as anti-aging and the photoprotective agent is still limited due to its solubility and stability in oily matrices or solutions balanced with the skin pH. In this research, CAF–ethyl cellulose (EC) microparticles were produced by water-in-oil-water double emulsion solvent evaporation encapsulation technique using a biocompatible polymer, EC, as a coating material and a surfactant, polyvinyl alcohol, as a stabilizer of the double emulsion. The study assessed the influence of formulation parameters as the solubility of the polymer in organic solvents and the polymer concentration on microparticles final characteristics. CAF–EC microparticles were characterized by product yield, encapsulation efficiency, mean particle size, particle size distribution and polydispersity and imaged by scanning light microscopy. In vitro release profiles were obtained in water and octanol to mimic oily based and water-based matrices balanced with the skin pH. In vitro release kinetics studies were carried out to investigate the release pattern of CAF in simulated cosmetic formulations. Both the product yield and the encapsulation efficiency were found to be dependent on the solubility of the polymer in the organic phase. The product yield was mainly affected by operational factors such as the sticking and the agglomeration of the polymer to the walls and the magnet stirring during microparticles hardening and results from the encapsulation efficiency revealed that an increase of the polymer concentration led to an increase of the encapsulation efficiency. The usage of a water-soluble solvent contributed to a decrease in the mean particle size and reduction of polydispersity with higher polymer concentrations. The polymer concentration, the polymer solubility in the organic phase and the amount of CAF entrapped shown to affect the release in water, whereas the release in octanol was mainly independent of the amount of CAF entrapped in EC microparticles. The double emulsion solvent evaporation technique and the assessment of the selected formulation conditions have given significant and innovative insights on the microencapsulation of bioactive ingredients for cosmetics formulations.     

Evaluation of isophorone diisocyanate crosslinked gelatin as a carrier for controlled delivery of drugs

The high solubility of gelatin in neutral, basic, and acidic biofluids may not promote a controlled drug delivery as a drug carrier. The present study reports the modification of the solubility and swellability of gelatin by crosslinking with hitherto uninvestigated isophorone diisocyanate to achieve controlled drug release characteristics. The crosslinked gelatin was insoluble and swellable in biofluids and analyzed by FT-IR and proton NMR, thermal analysis, swellability and biodegradability in simulated biofluids, X-ray diffraction, biocompatibility, and in vitro drug release kinetics and mechanism with 5-Fluorouracil as model drug. Crosslinking decreased the biodegradability and solubility, and enhanced the amorphous character of gelatin. The mild decrease in thermal stability of crosslinked gelatin was attributed to the urea linkage introduced. Drug release predominately occurred via anomalous transport mechanism with mild degradative diffusion. The observed results demonstrated that crosslinked gelatin can be used as a potential carrier to achieve controlled drug release.     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.