Sustained Drug Release Properties Research Articles

Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.

In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1 Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density optimization study revealed that cellular uptake efficiency of the hybrid NPs could be manipulated by controlling the surface-ligand densities. Furthermore, the cell uptake kinetics and mechanism studies showed that the dual-ligand modifications of hybrid NPs altered the cellular uptake pathway from caveolae-mediated endocytosis (CvME) to the multiple endocytic pathways, which would significantly enhance the NP internalization. Upon the systemic investigation of the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a hydrophobic anticancer drug, was successfully encapsulated into dual-ligand hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased burst release and a more gradual sustained drug release property. Because of the synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs exerted substantially better therapeutic potency against SK-BR-3 cancer cells than other NP formulations and free DTX drugs. These results demonstrate that the dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to treat breast cancer.

A simple way to synthesize 3D hierarchical HAp porous microspheres with sustained drug release

In this paper, a simple and environmentally friendly strategy was developed to synthesize the sphere-like hierarchical structures of HAp which was transformed by using flower-like CaHPO4 as a precursor in NaOH solution. Self-assembly flower-like CaHPO4 can be synthesized in mixed solvents of water and ethanol via microwave-assisted method. The effects of the reaction conditions on the morphology of the product were investigated and a possible formation mechanism was proposed. Furthermore, CaHPO4 microflowers can be transformed to HAp with sphere-like hierarchical structure with the assistance of microwave irradiation. These HAp porous microspheres exhibited high drug-loading capacity and sustained drug release properties due to their novel 3D hierarchical mesoporous structures and high specific surface area. Our study indicated that the fabricated hierarchical HAp porous microspheres might be a potential candidate as drug-delivery biomaterials for hard tissue repair.

A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of −26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

Alginate gel-coated oil-entrapped alginate–tamarind gum–magnesium stearate buoyant beads of risperidone

A novel alginate gel-coated oil-entrapped calcium-alginate–tamarind gum (TG)–magnesium stearate (MS) composite floating beads was developed for intragastric risperidone delivery with a view to improving its oral bioavailability. The TG-blended alginate core beads containing olive oil and MS as low-density materials were accomplished by ionotropic gelation technique. Effects of polymer-blend ratio (sodium alginate:TG) and crosslinker (CaCl2) concentration on drug entrapment efficiency (DEE, %) and cumulative drug release after 8h (Q8h, %) were studied to optimize the core beads by a 32 factorial design. The optimized beads (F–O) exhibited DEE of 75.19±0.75% and Q8h of 78.04±0.38% with minimum errors in prediction. The alginate gel-coated optimized beads displayed superior buoyancy and sustained drug release property. The drug release profiles of the drug-loaded uncoated and coated beads were best fitted in Higuchi kinetic model with Fickian and anomalous diffusion driven mechanisms, respectively. The optimized beads yielded a notable sustained drug release profile as compared to marketed immediate release preparation. The uncoated and coated Ca-alginate–TG–MS beads were also characterized by SEM, FTIR and P-XRD analyses. Thus, the newly developed alginate-gel coated oil-entrapped alginate–TG–MS composite beads are suitable for intragastric delivery of risperidone over a prolonged period of time.

Blood-compatible and biodegradable polymer-coated drug-eluting stent

A drug-eluting stent (DES) is a metal stent that has been coated with a drug known to suppress restenosis. To prepare a novel DES, a bare metal stent (BMS) was coated with sirolimus (SRL) in a blood-compatible, biodegradable polymer, poly lactic-glycolic acid, grafted with poly ethylene glycol (PLGA-PEG), by an ultrasonic spray method. The PLGA-PEG-coated DES was designed to control the drug release-rate by varying the PEG content in the polymer. The release behavior of SRL from the DES showed a burst-release pattern in 7 days and then sustained-release over 21 days. The amount of SRL released increased with increasing PEG content in the polymer up to 15%. The PLGA-PEG copolymer coated on the stent showed the potential to act as a bio-degradable drug reservoir. In an in vitro platelet adhesion test, the PLGA-PEG15-coated DES showed significantly reduced platelet deposition versus the BMS. The DES revealed anti-thrombotic activity and blood-compatibility presumably due to the increased hydrophilicity of the surface of the stent and the amount of SRL loading corresponding to the high PEG content in the polymer. In an animal study, the restenosis rate was reduced in the PLGA-PEG15-coated DES group (20.2±11.02%) versus the BMS group (44.2±12.11%). The PLGA-PEG15-coated DES inhibited smooth muscle cell (SMC) proliferation and prevented in-stent restenosis (ISR) in in vivo test. We successfully obtained the PLGA-PEG15-coated DES with smooth surface and sustained drug-release properties. Open image in new window

Polyelectrolyte complex based on carboxymethyl-kappa-carrageenan and Eudragit RL 30D as prospective carriers for sustained drug delivery

Interpolyelectrolyte complexation between carboxymethyl-kappa-carrageenan (CMKC), and Eudragit RL 30D (ERL) was studied and characterized. The obtained polyelectrolyte complex (PEC) was used to develop bioadhesive matrix tablets aimed to prolong buccal-residence time and sustain drug delivery. The optimum ERL-CMKC complexation weight ratio (7:3) was determined in distilled water using apparent viscosity and turbidity measurements. PEC properties were determined by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction and scanning electron microscopy (SEM). Miconazole matrix tablets were prepared by direct compression. Swelling properties and drug release in phosphate buffer solution medium (PBS, pH 6.8) were reported. Tablets exhibited extremely high swelling properties whereas; the dissolution data were fitted to different dissolution models. The drug release from matrix systems depends on the PEC concentration's and approaches zero order kinetics. Drug release mechanism is controlled by the superposition of diffusion and erosion. The relaxation phenomenon appears to increase along the release process and even overcomes diffusion for some systems. A PEC's optimal proportion of 65.06% in the tablet formula provides a dissolution profile characterized by Korsmeyer–Peppas exponent value (n) exceeding 0.97. The ERL-CMKC polyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with sustained drug release properties.

Fine granules showing sustained drug release prepared by high-shear melt granulation using triglycerin full behenate and milled microcrystalline cellulose

This study aimed to prepare fine granules with a diameter less than 200μm and sustained drug release properties by melt granulation. Triglycerin full behenate (TR-FB) was examined as a new meltable binder (MB) by comparison of its properties with those of glycerin monostearate (GM), widely used as MB. The effect of milling microcrystalline cellulose (MCC), an excipient for melt granulation, on the granule properties was also investigated. TR-FB was more stable during heating and storage than GM, and produced smaller granules with narrower particle size distribution, larger yield in the 106–200μm range, uniform roundness and better sustained drug release profile than those prepared with GM. Granules prepared with milled MCC had almost the same physicochemical properties as those produced with intact MCC. However, milled MCC produced granules with a more rigid structure and smaller void space than intact MCC. Consequently, the granules produced with milled MCC showed better sustained drug release behavior than those prepared with intact MCC. We successfully prepared fine granules with sustained drug release properties and diameter of less than 200μm using TR-FB and milled MCC.

Highly Mesoporous Silica Nanoparticles for Potential Drug Delivery Applications

There is an increasing interest in the use of silica nanoparticles (NPs) for bioapplications. Highly mesoporous fluorescein dye-doped silica NPs that can carry a drug payload have been successfully synthesized through a facile microemulsion process. The morphology of the as-prepared silica NPs were characterized by scanning electron microscope and transmission electron microscope, whereas their optical properties were studied by photoluminescence spectroscopy. The results revealed that these silica NPs exhibit excellent properties, including large pore volume, a narrow size distribution and strong fluorescent properties. The synthesized silica NPs showed a good biocompatibility and a low cytotoxicity when incubated in a murine fibroblast L-929 cell line. The obtained silica NPs were further used as drug delivery carriers to investigate the in vitro drug release properties using doxorubicin (DOX) as a representative drug model. It was shown that synthesized silica NPs well sustained drug release properties, suggesting their potential applications for drug delivery.

In-Vitro, Ex-Vivo Characterization of Furosemide Bounded Pharmacosomes for Improvement of Solubility and Permeability

The design of the present investigation was to prepare furosemide bounded pharmacosomes to enhance solubility and permeability drug by simple reproducible solvent evaporation technique and further investigated. Furosemide bounded pharmacosomes formulation (PMC1 & PMC2) was taken and compared with pure drug by way of enhanced solubility 5.4 fold in the water, 3.33, 4.76 fold in pH 7.4 and pH 5.8 respectively, increases permeability of furosemide bounded pharmacosomes 28.28% when compared with pure drug, drug content showed 94.83, N-octanol/water partition coefficient from 2.33 to 5.15 and in-vitro release profile exhibits excellent sustained drug release properties. Prepared furosemide bounded Pharmacosomes were confirmed from differential scanning calorimetry (DSC), X-ray diffraction (XRD) and FT-IR. The pharmacosomes reported amphiphilic nature may responsible for the improvement of solubility and permeability leads to enhancement of oral bioavailability. From this study it can be concluded that, this formulation strategy becomes important for drug belongs to the BCS class- II & IV.

Functionalized mesoporous silica nanoparticles with mucoadhesive and sustained drug release properties for potential bladder cancer therapy.

The synthesis of a series of β-cyclodextrin modified mesoporous silica nanoparticles with hydroxyl, amino, and thiol groups was described. A comparison of their mucoadhesive properties and potential as a drug delivery system for superficial bladder cancer therapy was made. The thiol-functionalized nanoparticles exhibit significantly higher mucoadhesivity on the urothelium as compared to the hydroxyl- and amino-functionalized nanoparticles. This is attributed to the formation of disulfide bonds between the thiol-functionalized nanoparticles and cysteine-rich subdomains of mucus glycoproteins. An anticancer drug, doxorubicin, was loaded into the mesopores of the thiol-functionalized nanoparticles, and sustained drug release triggered by acidic pH was achieved. The present study demonstrates that thiol-functionalized mesoporous silica nanoparticles are promising as a mucoadhesive and sustained drug delivery system for superficial bladder cancer therapy.

Development of drug delivery systems based on layered hydroxides for nanomedicine.

Layered hydroxides (LHs) have recently fascinated researchers due to their wide application in various fields. These inorganic nanoparticles, with excellent features as nanocarriers in drug delivery systems, have the potential to play an important role in healthcare. Owing to their outstanding ion-exchange capacity, many organic pharmaceutical drugs have been intercalated into the interlayer galleries of LHs and, consequently, novel nanodrugs or smart drugs may revolutionize in the treatment of diseases. Layered hydroxides, as green nanoreservoirs with sustained drug release and cell targeting properties hold great promise of improving health and prolonging life.

Drug delivery property, bactericidal property and cytocompatibility of magnetic mesoporous bioactive glass

A multifunctional magnetic mesoporous bioactive glass (MMBG) has been widely used for a drug delivery system, but its biological properties have been rarely reported. Herein, the effects of mesopores and Fe3O4 nanoparticles on drug loading–release property, bactericidal property and biocompatibility have been investigated by using mesoporous bioactive glass (MBG) and non-mesoporous bioactive glass (NBG) as control samples. Both MMBG and MBG have better drug loading efficiency than NBG because they possess ordered mesoporous channels, big specific surface areas and high pore volumes. As compared with MBG, the Fe3O4 nanoparticles in MMBG not only provide magnetic property, but also improve sustained drug release property. For gentamicin-loaded MMBG (Gent-MMBG), the sustained release of gentamicin and the Fe3O4 nanoparticles minimize bacterial adhesion significantly and prevent biofilm formation against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Moreover, the magnetic Fe3O4 nanoparticles in MMBG can promote crucial cell functions such as cell adhesion, spreading and proliferation. The excellent biocompatibility and drug delivery property of MMBG suggest that Gent-MMBG has great potentials for treatment of implant-associated infections.

Up-Conversion Nanoparticle Assembled Mesoporous Silica Composites: Synthesis, Plasmon-Enhanced Luminescence, and Near-Infrared Light Triggered Drug Release

A facile process for the preparation of multifunctional nanospheres combining several advantages of mesoporous channels, up-conversion (UC) luminescence, and photothermal responses into one single entity is reported. First, Gd2O3:Yb/Er assembled mesoporous silica with 2D hexagonal (MCM-41) and 3D cubic (MCM-48) network have been prepared via a one-step procedure. Then, gold nanocrystals with diameter of 5 nm are integrated with the amino group functionalized nanocomposites. Upon 980 nm near infrared (NIR) laser irradiation, a wavelength-dependent enhancement of the UC intensities is observed due to the surface plasmon resonance (SPR) effect of attached gold nanoparticles. These composites have good biocompatibility and sustained anticancer drug (doxorubicin, DOX) release properties, making it a promising candidate for drug delivery. Particularly, under 980 nm NIR laser irradiation, the green UC emission overlaps the SPR band of gold nanocrystals, which causes a photothermal effect of gold nanocrystals and induces a rapid DOX release from the Au hybrid materials. This DOX loaded multifunctional system has an obvious cytotoxic effect and photothermally killing enhanced effect on SKOV3 ovarian cancer cells. The endocytosis process was also demonstrated through confocal laser scanning microscope (CLSM) images. Such novel multifunctional anticancer drug delivery systems, which combine hyperthermia with the chemotherapeutic drugs by synergistic effect, should be of high potential in cancer therapy.

Cytochrome C capped mesoporous silica nanocarriers for pH-sensitive and sustained drug release.

In this paper, pH-responsive drug nanocarriers based on mesoporous silica nanoparticles (MSNs) capped with a natural, nontoxic protein cytochrome C (CytC) are designed and demonstrated for cancer therapy. At neutral pH the positively charged CytC can prevent the premature release of a preloaded anti-cancer drug. The results show that the CytC capped nanocarriers have excellent doxorubicin (DOX) loading efficiency (414 μg mg-1 MSN) and the leakage of the drug is only 16% at pH 7.4 phosphate-buffered saline for 72 h. Simultaneously, the DOX release percentage can reach 54% by decreasing the pH to 5.5. In contrast, unsealed MSNs show a fast DOX release rate at pH 7.4 and a slight pH-response. Confocal laser scanning microscopy demonstrates that the nanocarriers can enter human breast cancer MCF-7 cells and the DOX is sustained released from the drug carriers. Cytotoxicity tests and histological assays confirm that the constructed CytC capped nanocarriers possess lower toxicity than free DOX and unsealed drug carriers. Furthermore, intratumoral administration of the nanocarriers is significantly more efficacious in tumor reduction than free DOX and unsealed drug carriers in the xenograft models of MCF-7 cancer. Overall, this study demonstrates new drug nanocarriers with pH-sensitive and sustained drug release properties by using natural and nontoxic proteins as pore blockers to achieve highly efficient cancer treatment.

Hydrothermal fabrication of magnetic mesoporous carbonated hydroxyapatite microspheres: biocompatibility, osteoinductivity, drug delivery property and bactericidal property.

Implant-associated infection is a serious problem in orthopaedic surgery. Ideal bone filling materials should not only possess excellent biocompatibility, but also have good anti-infection property and osteoinductivity. Herein, magnetic mesoporous carbonated hydroxyapatite microspheres (MHMs) have been fabricated according to the following stages: (i) preparation of CaCO3/Fe3O4 microspheres; and (ii) hydrothermal transformation of magnetic calcium carbonate microspheres into MHMs. MHMs possess well-defined 3D nanostructures constructed by nanoplates as building blocks. The mesopores and macropores exist in and among the nanoplates, respectively. The porous structure makes the MHMs possess a great drug loading efficiency of 73-82%. Gentamicin-loaded MHMs display a sustained drug release property, and the controlled release of gentamicin can prevent biofilm formation against S. epidermidis. Moreover, the MHMs possess a magnetic property with a saturation magnetization strength of 3.98 emu g-1 because Fe3O4 nanoparticles are dispersed in the microspheres. The in vitro cell tests indicate that the magnetic nanoparticles in the MHMs not only promote the cell adhesion and proliferation of human bone marrow stromal cells (hBMSCs), but also stimulate the osteogenic differentiation. MHMs exhibit excellent biocompatibility, osteoinductivity, drug delivery property and bactericidal property, so they have great application potential for the treatment of complicated bone defects.

Synthesis and drug-loading properties of folic acid-modified superparamagnetic Fe3O4 hollow microsphere core/mesoporous SiO2 shell composite particles

A drug delivery system, which not only has superparamagnetic property, higher surface area but also has targeting function, has been developed. The core/shell structural magnetic magnetite mesoporous silica microspheres with amine groups (Fe3O4–SiO2–NH2) were first fabricated by a one-pot direct co-condensation method, then folic acid-modified magnetic mesoporous silica composite microspheres (Fe3O4–SiO2–NHFA) were obtained by the bonding of the Fe3O4–SiO2–NH2 with folic acid as targeted molecule. The resultant composite microspheres were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, low temperature nitrogen adsorption–desorption, and vibrating sample magnetometer. A well-known inflammational drug ibuprofen was used as a model drug to assess the loading and releasing behavior of the composite microspheres. Fe3O4–SiO2–NHFA system exhibits magnetic properties typical for superparamagnetic material with a higher saturation magnetization value of about 41.2 emu/g and has better capacity of drug storage (32.0 %) and sustained drug-release property. So this system has potential applications in biomedical field.

In vitro and in vivo studies on ocular vitamin A palmitate cationic liposomal in situ gels

N-trimethyl chitosan (TMC) with different degree of quaternization (DQ) as the coating materials, vitamin A palmitate (VAP)-loaded cationic liposomes dispersed in thermo-sensitive in situ gels (ISG) with poloxamer 407 (P407) as the base were prepared in this study. VAP-loaded liposomes (VAPL) were prepared using a film dispersion method followed by TMC-coating with DQ of 20%, 40% and 60% (TMC20, TMC40 and TMC60), respectively, then dispersed in P407 solution to obtain TMC-coated VAPL ISG. The in vitro properties of the system including morphology, size, zeta potential, entrapment efficiency, drug release and ocular retention were investigated. The ocular retention in vivo, eye irritation and pharmacokinetics in aqueous humor of the system were also studied in rabbits. VAPL revealed a spherical surface with mean size below 100 nm and negative zeta potential. After TMC-coating, the morphology and entrapment efficiency showed no significant changes, while the mean size was increased, zeta potential was changed into positive, and drug release was further sustained, and above all was influenced by DQ of TMC. TMC-coated VAPL exhibited little effect on the gelation temperature of P407 solution, and at the P407 concentration of 25% (w/v), TMC-coated VAPL ISG had the gelation temperature closest to the eye surface (34 °C) after diluted by the artificial tears. Compared with uncoated VAPL ISG and the marketed Oculotect gels, TMC-coated VAPL ISG displayed more retarded drug release and gel corrosion with a good linear relationship between them, and the higher DQ was, the slower drug release and gel corrosion. The ocular retention time in vitro and in vivo of TMC-coated VAPL ISG were both notable prolonged with a positive correlation with DQ of TMC. Compared with the marketed gels, TMC60-coated VAPL ISG showed delayed Tmax, improved Cmax and AUC(0–24) in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption. The local irritation of TMC-coated VAPL ISG was proved to be negligible. TMC-coated VAPL ISG with the properties of sustained drug release, prolonged ocular retention, improved corneal penetration and promising bio-safety is valuable to be studied further.

Hydrothermal fabrication of ZSM‐5 zeolites: Biocompatibility, drug delivery property, and bactericidal property

The bone graft-associated infection is widely considered in orthopedic surgery, which may lead to implant failure, extensive bone debridement, and increased patient morbidity. In this study, we fabricated ZSM-5 zeolites for drug delivery systems by hydrothermal method. The structure, morphology, biocompatibility, drug delivery property, and bactericidal property of the ZSM-5 zeolites were investigated. The ZSM-5 zeolites have mordenite framework inverted-type structure and exhibit the disk-like shape with the diameter of ∼350 nm and thickness of ∼165 nm. The biocompatibility tests indicate that human bone marrow stromal cells spread out well on the surfaces of the ZSM-5 zeolites and proliferate significantly with increasing culture time. As compared with the conventional hydroxyapatite particles, the ZSM-5 zeolites possess greater drug loading efficiency and drug sustained release property because of the ordered micropores, large Brunauer-Emmett-Teller (BET) surface areas, and functional groups. For the gentamicin-loaded ZSM-5 zeolites, the sustained release of gentamicin minimizes significantly bacterial adhesion and prevents biofilm formation against Staphylococcus epidermidis. The excellent biocompatibility, drug delivery property, and bactericidal property of the ZSM-5 zeolites suggest that they have great application potentials for treating implant-associated infections.

Triazole‐Containing Hydrogels for Time‐Dependent Sustained Drug Release

The purpose of this study is to develop novel triazole-containing hydrogels (TGs) as drug carrier and to investigate the sustained drug release accomplished by their time-dependent swelling behavior. The synthetic pathway of TGs includes: (1) DCC-coupling on hydroxyethyl methacrylate (HEMA) to prepare HEMA-alkyne (HA), (2) click-coupling to prepare a triazole-ring-containing monomer (TM), and (3) the synthesis of a series of TGs. The aggregation between triazole rings is found to be responsible for drug release controllability. Rhodamine 6G is studied as a model anticancer drug for release experiments. The effects of pH and temperature on the properties of sustained drug release are also studied.

Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant K a was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.