High Drug Loading Ability Research Articles

Controllable Microfluidic Production of Drug-Loaded PLGA Nanoparticles Using Partially Water-Miscible Mixed Solvent Microdroplets as a Precursor

We present a versatile continuous microfluidic flow-focusing method for the production of Doxorubicin (DOX) or Tamoxifen (TAM)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). We use a partially water-miscible solvent mixture (dimethyl sulfoxide DMSO+ dichloromethane DCM) as precursor drug/polymer solution for NPs nucleation. We extrude this partially water-miscible solution into an aqueous medium and synthesized uniform PLGA NPs with higher drug loading ability and longer sustained-release ability than conventional microfluidic or batch preparation methods. The size of NPs could be precisely tuned by changing the flow rate ratios, polymer concentration, and volume ratio of DCM to DMSO (VDCM/VDMSO) in the precursor emulsion. We investigated the mechanism of the formation of NPs and the effect of VDCM/VDMSO on drug release kinetics. Our work suggests that this original, rapid, facile, efficient and low-cost method is a promising technology for high throughput NP fabrication. For the two tested drugs, one hydrophilic (Doxorubicin) the other one hydrophobic (Tamoxifen), encapsulation efficiency (EE) as high as 88% and mass loading content (LC) higher than 25% were achieved. This new process could be extended as an efficient and large scale NP production method to benefit to fields like controlled drug release and nanomedicine.

Black TiO2 based core-shell nanocomposites as doxorubicin carriers for thermal imaging guided synergistic therapy of breast cancer.

TiO2 nanomaterials have been widely used for anticancer drug carriers and UV/980 nm NIR triggered cancer synergistic platforms. However, traditional pure TiO2 nanocarriers encounter some serious drawbacks, such as low drug loading ability, limited tissue penetration of UV light, and heating effect of 980 nm NIR on normal tissue, which obstruct their further application in cancer treatment. To overcome those challenges, novel mesoporous silica (mSiO2) coated black TiO2 core-shell nanocomposites are designed and constructed as doxorubicin carriers for 808 nm NIR triggered thermal imaging guided photothermal therapy combined chemotherapy of breast cancer. Properties of the nanocomposites such as micro-morphology, size, drug loading ability and release, targeting performance, and therapy efficiency in vitro and in vivo were evaluated. The results indicated the core-shell nanocomposites with dramatically increased loading ability were pH-responsive/NIR-accelerated doxorubicin release nanocarriers and showed synergistic breast cancer treatment in vitro and in vivo. This study verifies that the newly prepared mSiO2 coated black TiO2 core-shell nanocarriers can overcome the limitations of traditional TiO2 nanocarriers and thus improve and broaden usage of TiO2 nanoparticles in nanomedicine.

Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery

This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. <10.0% IBU was released under artificial gastric fluid after 2h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs.

Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug.

Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Nanotechnology is widely used in fiber and textiles, electronics, space, agriculture, forensic science and medical therapeutics. It increasingly plays a significant role in drug delivery system. Compared with traditional delivery system, the nanoparticle drug delivery system has lots of merits, such as the high drug loading ability, the excellent biocompatibility, low toxicity, controlled and targeted drug release. We undertook a structured research of biodegradable polymeric nanoparticles used as delivery carrier for drug using a focused review question and inclusion/exclusion criteria. We have searched the bibliographic databases for peerreviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analysis the findings. Seventy-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for drug in therapeutic applications and developments. Seven papers outlined the superiority characteristics of polymeric nanoparticles that applied in the field of vaccine. Forty-seven papers overviewed the application prospects of polymeric nanoparticles used as drug delivery carrier for cancer. These included current advances in research and clinical applications of polymeric nanoparticles. The review identified the drug delivery carrier of biodegradable polymeric nanoparticles, and we described the synthesis methods, applications and challenges of polymeric nanoparticles. The findings of this review identified that the biodegradable polymeric nanoparticles were used as delivery carrier for drug currently. It also indicates that the biodegradable polymeric nanoparticles play an important role in the drug delivery.

5-Fluorouracil Loaded Chitosan-PVA/Na+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity.

In the present study, chitosan and polyvinyl alcohol (PVA) were blended with different concentrations of sodium montmorillonite (Na+MMT) clay solution by a solvent casting method. X-ray diffraction and transition electron microscope results show that the film properties are related to the co-existence of Na+MMT intercalation/exfoliation in the blend and the interaction between chitosan–PVA and Na+MMT. 5-Fluorouracil (5-FU) was loaded with chitosan–PVA/Na+MMT nanocomposite films for in vitro drug delivery study. The antimicrobial activity of the chitosan–PVA/Na+MMT films showed significant effect against Salmonella (Gram-negative) and Staphylococcus aureus (Gram-positive), whereas 5-FU encapsulated chitosan–PVA/Na+MMT bio-nanocomposite films did not show any inhibition against bacteria. Our results indicate that combination of a flexible and soft polymeric material with high drug loading ability of a hard inorganic porous material can produce improved control over degradation and drug release. It will be an economically viable method for preparation of advanced drug delivery vehicles and biodegradable implants or scaffolds.

Enteric polymer based on pH-responsive aliphatic polycarbonate functionalized with vitamin E to facilitate oral delivery of tacrolimus.

To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)-poly(2-methyl-2-carboxyl-propylene carbonate)-vitamin E, mPEG-PCC-VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113-PCC32-VE4 exhibited low critical micelle concentration of 1.7 × 10(-6) mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113-PCC32-VE4 micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.

Theranostic magnetoliposomes coated by carboxymethyl dextran with controlled release by low-frequency alternating magnetic field.

The aim of this work was to construct carboxymethyl dextran (CMD)-coated magnetoliposomes (MLs), another stealth MLs alternative to PEGylated MLs, for theranostic application. Particularly, the on-demand release of CMD-MLs under low-frequency alternating magnetic field (LF-AMF) was studied. We found that as-prepared MLs exhibited good stability and high drug loading ability for doxorubicin (DOX). Cytotoxicity assay against human neuroblastoma SH-SY5Y cells showed that the DOX-loaded CMD-MLs were less toxic than free DOX due to the sustained release of DOX. However, the release of DOX-loaded CMD-MLs was enhanced by low-frequency alternating magnetic field without hyperthermia generation. The MLs also acted as an efficient T2-weighted contrast agent during in vitro MRI measurements. The above results provide useful information on in vivo diagnostic/therapeutic efficacy of DOX-loaded CMD-MLs for some cancers, such as brain cancers.

Theranostics of Epitaxially Condensed Colloidal Nanocrystal Clusters, through a Soft Biomineralization Route

Clustering of biocompatible magnetic iron oxide nanocrystallites (MIONs) is a synthetic strategy which improves magnetic manipulation, imaging, and sensing for biomedical applications. In this work we describe the synthesis of condensed clustered MIONs obtained through biomineralization and epitaxial aggregation in the presence of alginate at ambient conditions, mimicking the process that so far has been achieved only by nature, in iron-oxidizing bacteria. These condensed-type magnetic nanostructures exhibit higher magnetophoretic responses compared to other types of magnetic colloids and clustered systems. The soft environmental conditions used for the synthesis of the magnetic nanosystems enables the alginate coating material to retain high drug loading ability for the doxorubicin molecule as well as strong binding proclivity for radionuclides. The strong binding of doxorubicin forms the physical basis to obtain magnetic nanocarriers, where the selective release of the drug occurs only under the action ...

FABRICATION AND IN VITRO EVALUATION OF FOLATE-MODIFIED IRON FERRITE NANOPARTICLES WITH HIGH DOXORUBICIN LOADING FOR RECEPTORS-MAGNETIC-GUIDED DRUG DELIVERY

Folate-modified iron ferrite nanoparticles with high doxorubicin loading (FDMP) were developed for dual targeting of tumor cells. Large quantities of doxorubicin and folate ligand were chemically coupled to the synthesized dual-functional magnetic nanoparticles by using the multihand cross-linker poly-L-glutamic acid. FDMP exhibits high drug loading ability, narrow size distribution and pH sensitivity to drug release. The drug loading ratio and the magnetic response can be adjusted by controlling the reactant ratio. FDMP possesses high magnetic-guided ability and exhibits enhanced uptake by folate receptors expressing tumor cells and increased cancer cell cytotoxicity.

Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer

Lung metastasis is one of the greatest challenges for breast cancer treatment. Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first designed to inhibit the lung metastasis of breast cancer effectively. DOX was non-covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE-PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug loading and excellent ability to deliver DOX to the nucleus, thereby significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore, DNX showed good histocompatibility and could improve drug accumulation in lung, as a result, markedly inhibited the lung metastasis of breast cancer. The high anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX could be a promising drug delivery system for the therapy of lung metastasis of breast cancer.

Adsorption Behavior of Pazufloxacin Mesilate on Amino-Functionalized Carbon Nanotubes

In this study, the interaction between amino-functionalized multi-walled carbon nanotubes (e-MWNTs) and antibacterial agents was investigated and the drug-loading ability of e-MWNTs was evaluated. The e-MWNTs were prepared and characterized, then were used as adsorbents for loading an antibacterial agent, pazufloxacin mesilate (PZFX). The adsorption behavior of PZFX on e-MWNTs in water was investigated. The results showed that e-MWNTs were able to form supramolecular complexes with PZFX and could be used as drug carriers with high drug-loading efficiency. Compared with pristine multi-walled carbon nanotubes (MWNTs), the adsorption efficiency of e-MWNTs was better. In kinetic studies, the pseudo-second-order model showed satisfactory fitting and good adsorption process. Langmuir model was successfully employed to describe the adsorption isotherms of PZFX on e-MWNTs and higher drug-loading ability were observed from e-MWNTs with smaller diameter. The adsorption process of e-MWNTs was sensitive to the pH and it was observed that the neutral pH gave the best adsorption. Low temperatures facilitated the adsorption process. In addition, the release process of PZFX from e-MWNTs occurred in two stages: a rapid release, then followed by a slow release, in which acidic solution favored the release process. In summary, our technique developed for the adsorption of PZFX on e-MWNTs is satisfactory.

Hybrid nanostructured drug carrier with tunable and controlled drug release

We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery.

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells – both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.

Bioactive SrO–SiO2 glass with well-ordered mesopores: Characterization, physiochemistry and biological properties

For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO2 in an effort to develop a bioactive mesoporous SrO–SiO2 (Sr–Si) glass with the capacity to deliver Sr2+ ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr2+ on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr–Si glass were investigated. The prepared mesoporous Sr–Si glass was found to have an excellent release profile of bioactive Sr2+ ions and dexamethasone, and the incorporation of Sr2+ improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr–Si glass had no cytotoxic effects and its release of Sr2+ and SiO44− ions enhanced alkaline phosphatase activity – a marker of osteogenic cell differentiation – in human bone mesenchymal stem cells. Mesoporous Sr–Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr2+ into mesoporous SiO2 glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications.

Adsorption behavior of epirubicin hydrochloride on carboxylated carbon nanotubes

The aim of this study was to understand the interaction between carboxylated carbon nanotubes (c-CNTs) and anticancer agents and evaluate the drug-loading ability of c-CNTs. We prepared carboxylated multi-walled carbon nanotubes (c-MWNTs) with nitric acid treatment, then evaluated the adsorption ability of c-MWNTs as adsorbents for loading of the anticancer drug, epirubicin hydrochloride (EPI), and investigated the adsorption behavior of EPI on c-MWNTs. Unmodified multi-walled carbon nanotubes (MWNTs) and single-walled carbon nanotubes (SWNTs) were included as comparative adsorbents. The results showed that carbon nanotubes were able to form supramolecular complexes with EPI via π–π stacking and possessed favorable loading properties as drug carriers. The Freundilich adsorption model was successfully employed to describe the adsorption process. Because of the high surface area and hydrogen bonding, c-MWNTs’ adsorption efficiency was the highest and the most stable and their drug-loading capacity was superior to that of MWNTs. With the increase of pH, the adsorption capacity of EPI on the c-MWNTs increased. Low-temperature facilitated the adsorption. More rapid EPI adsorption rate and higher drug-loading ability were observed from c-MWNTs with smaller diameter. Moreover, the adsorption kinetics of EPI on c-MWNTs could be well depicted by using the pseudo-second-order kinetic model.