Chemotherapeutic Delivery Systems Research Articles

Co-delivery of Bcl-2 siRNA and doxorubicin using liposome-incorporated poly(ε-caprolactone) /chitosan nanofibers for the treatment of lung cancer

The small interfering RNA (siRNA) and chemotherapeutic drugs-incorporated liposome-nanofiber hybrid delivery system could inhibit tumor growth and decrease the adverse side effects. In the present study, doxorubicin (DOX) anticancer drug and Bcl-2 siRNA have been incorporated into the liposome-embedded chitosan-poly (ethylene oxide)/poly (ε-caprolactone) (CS/PEO/PCL) pH-sensitive nanofibrous hybrid formulation for treating lung cancer. The mean particle size & zeta potential of liposome, DOX-liposome, and DOX-Bcl-2-liposome were 130 ± 10 nm & 27.85 ± 1.65 mV, 155 ± 15 nm & 26.30 ± 1.3 mV, and 195 ± 30 nm &11.31 ± 0.65 mV, respectively. The average diameter of electrospun CS/PEO/PCL/DOX-siRNA-liposome simple and CS/PEO/PCL/DOX-siRNA-liposome core-shell nanofibers was 385 ± 80, and 485 ± 100 nm, respectively. The extended release of DOX and si-RNA (30 days) were achieved from DOX-Bcl-2-liposome-incorporated CS/PEO/PCL core-shell nanofibers. The maximum down-regulation of Bcl-2 siRNA, apoptosis of cancer cells, and reduction in the cell viability of A549 lung carcinoma cells were achieved using DOX-Bcl-2 liposome-incorporated CS/PEO/PCL core-shell nanofibers. The in vivo results indicated the maximum suppress of tumor growth without change in the body weight for the mice treated with DOX-Bcl-2 liposome-incorporated CS/PEO/PCL nanofibers. The obtained results demonstrated that the prepared hybrid delivery system presented a novel effective formulation for treating lung cancer.

Controlled Dissociation of Polymeric Micelles in Response to Oxidative Stress.

Nanoparticle-based drug carriers that can respond to oxidative stress in tumor tissue have attracted attention for site-specific drug release. Taking advantage of the characteristic microenvironment in tumors, one of the attractive directions in drug delivery research is to design drug carriers that release drugs upon oxidation. A strategy to incorporate oxidation-sensitive thioether motifs such as thiomorpholine acrylamide (TMAM) to drug carriers has been often used to achieve oxidation-induced dissociation, thereby targeted drug release. However, those delivery systems often suffer from a slow dissociation rate due to the intrinsic hydrophobicity of the thioether structures. In this study, we aimed to enhance the dissociation rate of TMAM-based micelles upon oxidation. The random copolymers of N-isopropylacrylamide and TMAM (P(NIPAM/TMAM)) were designed as an oxidation-sensitive segment that showed a fast response to oxidative stress. We first synthesized P(NIPAM/TMAM) copolymers with different NIPAM:TMAM molar ratios. Those copolymers exhibited low critical solution temperatures (LCSTs) below 32 °C, which shifted to higher temperatures after oxidation. The changes in LCSTs depend on the NIPAM:TMAM molar ratios. At the NIPAM:TMAM molar ratio of 82:18, the LCSTs before and after oxidation were 17 and 54 °C, respectively. We then prepared micelles from the diblock copolymers of poly(N-acryloyl morpholine) (PAM) and P(NIPAM/TMAM). The micelles showed an accelerated dissociation rate upon oxidation compared to the micelles without NIPAM units. Furthermore, the doxorubicin (Dox)-loaded micelles showed enhanced relative toxicity in human colorectal cancer (HT29) cells over human umbilical vein endothelial cells (HUVECs). Our novel strategy to design an oxidation-sensitive micellar core comprising a P(NIPAM/TMAM) segment can be used as a chemotherapeutic delivery system that responds to an oxidative tumor microenvironment in an appropriate time scale.

‘TRAIL’ of targeted colorectal cancer therapy

TRAIL, a tumor necrosis factor-related apoptosis-inducing ligand is a member of the tumor necrosis factor (TNF) superfamily, which is a cytokine that has shown a particularly precise and selective affinity towards death receptors that are overexpressed in cancer cells. While leaving the normal cells intact and unharmed, due to this property it has been the ligand of choice for highly precise cancer chemotherapeutic delivery system development. On numerous occasions, TRAIL has been used singularly and in combination with other drugs. It was observed that TRAIL had a tendency to be susceptible in terms of the cancer cells developing resistance against it. So TRAIL monotherapy was a bit of a rough patch for the molecule to become successful in the chemotherapy universe, however the conjugations and synergistic actions of TRAIL opened up new horizons which are discussed in this review with specific interest on colorectal cancer (CRC).

Electrospun Poly(acrylic acid-co-4-styrene sulfonate) as Potential Drug-Eluting Scaffolds for Targeted Chemotherapeutic Delivery Systems on Gastric (AGS) and Breast (MDA-Mb-231) Cancer Cell Lines.

Potential drug-eluting scaffolds of electrospun poly(acrylic acid-co-styrene sulfonate) P(AA-co-SS) in clonogenic assays using tumorigenic gastric and ovarian cancer cells were tested in vitro. Electrospun polymer nanofiber (EPnF) meshes of PAA and PSSNa homo- and P(AA-co-SS) copolymer composed of 30:70, 50:50, 70:30 acrylic acid (AA) and sodium 4-styrene sulfonate (SSNa) units were performed by electrospinning (ES). The synthesis, structural and morphological characterization of all EPnF meshes were analyzed by optical and electron microscopy (SEM-EDS), infrared spectroscopy (FTIR), contact angle, and X-ray diffraction (XRD) measurements. This study shows that different ratio of AA and SSNa of monomers in P(AA-co-SS) EPnF play a crucial role in clonogenic in vitro assays. We found that 50:50 P(AA-co-SS) EPnF mesh loaded with antineoplastic drugs can be an excellent suppressor of growth-independent anchored capacities in vitro assays and a good subcutaneous drug delivery system for chemotherapeutic medication in vivo model for surgical resection procedures in cancer research.

PD-L1-Targeted Co-Delivery of Two Chemotherapeutics for Efficient Suppression of Skin Cancer Growth.

To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this purpose, we co-loaded a conventional antiworm drug, albendazole (ABZ), and a TOPK inhibitor, OTS964, into lipid-coated calcium phosphate (LCP) nanoparticles for skin cancer treatment. OTS- and ABZ-loaded LCP (OTS-ABZ-LCP) showed a synergistic cytotoxicity against skin cancer cells through their specific cancerous pathways, without obvious toxicity to healthy cell lines. Moreover, dual-targeting the programmed death ligand-1 (PD-L1) and folate receptor overexpressed on the surface of skin cancer cells completely suppressed the skin tumour growth at low doses of ABZ and OTS. In summary, ABZ and OTS co-loaded dual-targeting LCP NPs represent a promising platform with high potentials against complicated cancers where PD-L1/FA dual targeting appears as an effective approach for efficient and selective cancer therapy.

Biointerface engineering of self-protective bionic nanomissiles for targeted synergistic chemotherapy

Erythrocyte membrane (EM)-camouflaged chemotherapeutic delivery nanovehicles hold promise for solid tumor therapy because of their excellent biostability and biocompatibility. However, it is accompanied with insufficient targeting effect and deficient pharmacokinetic behavior due to the lack of a regulated biointerface to navigate and overcome biological transportation obstacles in solid tumor therapy. Herein, an anti-epidermal growth factor receptor (EGFR) aptamer (EApt) modified and EM-cloaked chemotherapeutic nanomissile delivery system was constructed. The anchored-EApt acting as a specific EGFR suppressor promotes to inhibit the overexpression of EGFR and initiate the cell apoptosis. Importantly, the resulting PLGA-DOX@EM-EApt orchestrated the bioactivity of each component and provided synergistic cell apoptosis and antitumor effects by precisely suppressing EGFR expression levels and delivering DOX. The in vitro and in vivo experimental results confirmed that the immune escape and active targeting behaviors of PLGA-DOX@EM-EApt could significantly promote its drug retention and tumor inhibition abilities. Our findings propose a novel strategy using the biointerface functionalization technique, demonstrating a promising therapeutic platform via a biomimetic drug delivery system for precise solid tumor recognition and synergistic therapy.

Development of bioflavonoid containing chemotherapeutic delivery systems for UV-damaged skin and kangri cancer

Abstract Background The lower abdomen and inner thighs are most likely to become affected by kangri cancer because those areas are exposed to continuous exposure to kangri. Objective In this article, formulation and characterization of a water-in-oil microemulsion of 5-fluorouracil with rutin (R-5FU) for better skin penetration and inhibition of kangri cancer (skin cancer surfactant) is discussed. Method To produce R-5-FU microemulsions, surfactant-cosurfactant was mixed with oil. Distilled water was added dropwise with the help of a burette by gentle stirring at a constant temperature. The surfactant and co-surfactant were mixed into three particular ratios 1:1, 2:1, and 3:1. Further characterizations were performed, such as visual inspection and thermodynamic stability including a stress test and centrifugation. In visual inspection included assessment of the colour, homogeneity, and odour of the formulation of FU microemulsion. Result All three microemulsions, labeled RME1, RME2, and RME3, are highly stable. An oval shape of surface morphology of 5-FU was noticed by using a TEM image. The viscosity of RME3 was found to be 17.25±0.22 pa-s. The average globule size was 100–300 nm for all three RME. The results of human cadaver skin permeability are almost of the same pattern, butRME3 indicates the best skin permeability with negligible side effects on the skin. Conclusion The quantity of 5-FU released from all formulations at 3-hr ranged from 95.57% to 83.67%. None of the three formulations resulted in skin irritation, with irritancy score of zero (IS=0). Observation revealed no lysis, hemorrhage, or coagulation after application.

Sequential Release of Paclitaxel and Imatinib from Core-Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer.

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.

Synthesis and characterization of poly(N-vinycaprolactam)-grafted gold nanoparticles by free radical polymerization for using as chemotherapeutic delivery system

This work reports the grafting of a stimuli-responsive polymer onto the surface of gold nanoparticles (AuNPs). First, AuNPs were synthesized by reduction of chloroauric acid (HAuCl4) aqueous solution with sodium citrate. Then, AuNPs were functionalized with allyl thiol to obtain allyl-functionalized AuNPs (AuNPs-SH). A “grafting from” approach was used to graft poly(N-vinylcaprolactam) (PNVCL) by free radical polymerization to obtain nanocomposites based on AuNPs (AuNPs-g-PNVCL).Nanocomposites were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Covalent interactions between AuNPs and PNVCL were investigated by XPS and FTIR studies while the structural and morphological characteristics were studied by TEM and XRD analysis respectively. PNVCL-modified AuNPs were able to load doxorubicin (DOX) because of the presence of polymer and the in vitro drug release profiles showed a sustained release of this drug during the first 24 h at 37 °C.

PHA-Based Thermogel as a Controlled Zero-Order Chemotherapeutic Delivery System for the Effective Treatment of Melanoma.

Promising applications of poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx) in tissue engineering have been extensively investigated. However, the application of PHBHx in drug delivery has been rarely explored due to its hydrophobic property, limited functionality, and the absence of active groups for reaction. In this work, PHBHx has been functionalized and copolymerized with poly(ethylene glycol) (PEG) and polypropylene glycol (PPG) oligomers to provide a series of novel PHBHx incorporated polyurethanes (PHxEP). In vitro docetaxel (DTX) release showed that DTX loaded thermogel can achieve sustained, zero-order release of DTX, that is, constant 10% release of the payload up to 10 days, which is unique and different from other systems previously reported. The inhibition effect of DTX loaded thermogel on solid tumors was evaluated using mouse tumor models, and its biosafety was evaluated. DTX-loaded thermogel showed enhanced antimelanoma effect on melanoma solid tumors compared to the free DTX drug and no apparent harm to other tissues including liver, heart, spleen, kidney, and lung tissues. The results indicated that the PHxEP-based thermogel can be a hopeful drug delivery candidate for sustained and constant delivery of anticancer drugs. It is the first time that the functionalized PHBHx-based water-soluble thermogels have been reported as the drug carrier for DTX release.

Identifying a Membrane-Type 2 Matrix Metalloproteinase-Targeting Peptide for Human Lung Cancer Detection and Targeting Chemotherapy with Functionalized Mesoporous Silica.

Membrane-type 2 matrix metalloproteinase (MT2-MMP) is critical for the aggressive lung tumor growth, progression, and metastasis. Here, to obtain the peptides in binding specifically to MT2-MMP, a phage-displayed 12 peptide library was used and the affinity of peptides toward MT2-MMP was identified by multitest methods. The results showed that a specific MT2-MMP-targeting peptide with the sequence of HHRLHSAPPPQA (MT2-AF5p) exhibited a high specificity and strong affinity against lung tumors. To further achieve specific targeting and precise therapeutic effects, MT2-AF5p was conjugated onto fluorescent mesoporous silica nanoparticles (FMSN-NH2) and loaded with doxorubicin (DOX) to construct a chemotherapeutic drug-targeting delivery system (DOX-loaded FMSN@MT2-AF5p). The DOX-loaded FMSN@MT2-AF5p achieved a boost in DOX release in an acidic environment. Most importantly, FMSN@MT2-AF5p efficiently targeted the tumor area, as seen in the fluorescent imaging ex vivo. The novel peptide-functionalized nanoparticles with a good biocompatibility are promising for clinical use as a precise targeting nanodrug for lung cancer diagnosis and therapy.

Mesoporous Silica Nanoparticles for Targeted and Stimuli‐Responsive Delivery of Chemotherapeutics: A Review

AbstractMesoporous silica nanoparticles (MSNs) exhibit the typical characteristics of inorganic materials that make them promising drug delivery carriers for cancer therapy. Their structural properties allow the targeted delivery of chemotherapeutic drugs to enhance drug efficacy and reduce adverse effects. The functionalization of MSNs with targeting ligands to a specific tissue/cell and stimuli‐responsive capping materials to seal drugs inside the MSNs pores are widely studied for biomedical and pharmaceutical applications. Furthermore, multiple stimuli‐responsive MSN‐based drug delivery systems are developed to enhance the delivery of anticancer drugs to their specific target and thereby improve the release of the drugs at the intended site. In addition, several toxicity studies are conducted to evaluate the biosafety and biocompatibility of MSNs. Although MSNs present reduced toxicity compared to colloidal silica, they can induce cytotoxicity associated with oxidative stress by increased reactive oxygen species production and decreased glutathione levels that can ultimately lead to cell death. However, different modifications to control morphology and surface composition can be applied to overcome the biocompatibility concerns. In this review, a comprehensive overview of the controlled synthesis, functionalization, targeting and biocompatibility of MSNs, as well as their biomedical application as a chemotherapeutic delivery system is provided.

Advances in the Delivery of Cancer Therapeutics: A Comprehensive Review.

The effects of various chemotherapeutic agents have been assessed for their capacity to inhibit the cell replication in variety of cancer cases. At present there are more than hundred chemotherapeutic agents capturing worth 42 billion dollar of drug market. The major obstacle in the successful treatment of cancer is the obnoxious side effects of chemotherapeutics and multi drug resistance, which deteriorates the quality of life of cancer patient. This article attempts to summarize different novel chemotherapeutic delivery systems which aim to circumvent these unwanted effects. Areas Covered: Outcomes of different tumor directed carrier systems have been discussed with special emphasis on nanocarriers systems, drug polymer conjugation, directly implantable matrices and others. In addition, combination therapy and immunotherapy are also discussed as a revolutionary alternative. Even though significant contributions have been made in the development of carrier systems for the chemotherapeutic agents, merits and demerits of all the avenues should be critically examined. Potential of all novel strategies should be exploited by critically evaluating their strength, weakness, opportunities and threats. Further, clinical trials based on revised and critically scrutinized frameworks and protocols are needed so that the efficiency and safe action of these new systems can be guaranteed in cancer patients.

An intratumoral injectable, electrostatic, cross-linkable curcumin depot and synergistic enhancement of anticancer activity

In this study, we describe an intratumoral injectable, electrostatic, cross-linkable curcumin (Cur) drug depot to enhance anticancer activity. The key concept in this work was the preparation of an electrostatic, cross-linked carboxymethyl cellulose (CMC) and chitosan (CHI) hydrogel containing Cur-loaded microcapsules (Cur-M). The CMC and CHI solutions existed as a liquid before mixing and formed a CMC and CHI (CCH) hydrogel as a drug depot after mixing via electrostatic interactions between the anionic CMC and cationic CHI. Compared with the individual CMC and CHI solutions, the electrostatic, cross-linked CCH depot persisted in vivo for an extended period. The prepared Cur-M was easily mixed with the CMC and CHI solutions. Cur-M/CMC and Cur-;M/CHI solutions easily formed Cur-M-loaded CCH depots after simple mixing. The in vitro and in vivo Cur-M-loaded CCH depot was designed with Cur-M dispersed inside an outer shell of electrostatically cross-linked CCH. The Cur-M-loaded CCH depot produced greater inhibition of tumor growth than did Cur-M, whereas single and repeated injections of free Cur had the weakest inhibitory effects. The results of this study indicate that the electrostatic, cross-linked, Cur-M-loaded CCH depot described in this study can synergistically enhance anticancer activity in chemotherapeutic delivery systems.

Design of novel chemotherapeutic delivery systems for colon cancer therapy based on oral polymeric nanoparticles.

Oral delivery of cancer chemotherapeutic drugs (CCDs) is subject matter in the 21st century, which changes the dosage regimens of oncotherapy with enhancement in patient's life and deducts the cost of therapy. The present report explored on the nano-oncology such as polymeric nanoparticles (PNPs) as an oral CCDs delivery vehicle, showing great potential for colon cancer treatment. Proof-of-concept in vitro and in vivo results for delivery of CCDs using various oral PNPs are included in this review from the literatures. Subsequently, the gastrointestinal barriers for oral chemotherapy have been highlighted. Furthermore, PNPs achieving better accumulation in the cancer region by desirable quality of their passive- and active-targeting phenomena have also been highlighted.

Drug Coated Clay Nanoparticles for Delivery of Chemotherapeutics

Purpose: Osteosarcoma (OSA) is the most common malignancy of bone in children and adolescents. Standard treatments include adjuvant chemotherapy, radiotherapy, hormone or biological therapy, and if OSA is refractory, surgical ablation of the primary tumor. Advancements in treatment modalities have led to increased rates of ‘limb-sparing’ surgeries, but patients are still threatened with the risk of recurrence. New chemotherapeutic delivery systems and strategies are needed to improve treatment options and patient outcomes. Methods: Halloysite nanotubes (HNTs) exhibit high levels of cytocompatibility and biocompatibility and have been show to be effective at sustained drug release. HNTs were coated with the polyelectrolytes (PE), polyvinylpyrrolidone and polyacrylic acid, and methotrexate (MTX) infused within the coating layers. MTX release and cytotoxicity studies were used to assess the effectiveness of the coatings in inhibiting osteosarcoma cell growth. Results: Polyelectrolyte coatings provided sustained release of MTX and, in an in-vitro study, were show to be effective in altering osteosarcoma cell morphology and reducing the rate of cell proliferation. We further show that MTX-coated halloysite nanotubes can be added to a polymer, Nylon-6; the MTX released, and still retain its ability to inhibit osteosarcoma cell growth. Conclusion: HNT/MTX encapsulated complexes inhibited osteosarcoma cell proliferation and show potential as a delivery vehicle for the prevention of tumor metastasis and/or tumor recurrence after surgery. Keywords: Drug delivery, halloysite, methotrexate, osteosarcoma, polyelectrolytes.

Cyclodextrin-based Polymeric Nanoparticles as Efficient Carriers for Anticancer Drugs

Among the difficulties encountered in the treatment of cancer are the physico-chemical properties of the chemotherapeutic agents; in particular low water solubility and low stability, resulting in poor efficacy. Due to their capability to form molecular inclusions with apolar molecules (or part of them) cyclodextrins constitute a powerful tool to prepare more efficient chemotherapeutic delivery systems such as nanoparticles. This review focuses on polymeric nanoparticles for cancer therapy prepared from either cyclodextrin molecules, or polymer and cyclodextrins.

Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot

Here, we describe combinational chemotherapy via intratumoral injection of doxorubicin (Dox) and 5-fluorouracil (Fu) to enhance the efficacy and reduce the toxicity of systemically administered Fu and Dox in cancer patients. As the key concept in this work, mixture formulations of Dox-loaded microcapsules (Dox-M) and Fu-loaded Pluronic® hydrogels (Fu-HP) or Fu-loaded diblock copolymer hydrogels (Fu-HC) have been employed as drug depots. The in vitro and in vivo drug depot was designed as a formulation of Dox-M dispersed inside an outer shell of Fu-HP or Fu-HC after injection. The Dox-M/Fu-HP and Dox-M/Fu-HC formulations are free flowing at room temperature, indicating injectability, and formed a structural gelatinous depot in vitro and in vivo at body temperature. The Fu-HP, Fu-HC, Dox-M/Fu-HP, Dox-M/Fu-HC, and Dox-M formulations were easily injected into tumor centers in mice using a needle. Dox-M/Fu-HC produced more significant inhibitory effects against tumor growth than that by Dox-M/Fu-HP, while Fu-HP, Fu-HC and Dox-M had the weakest inhibitory effects of the tested treatments. The in vivo study of Dox and Fu biodistribution showed that high Dox and Fu concentrations were maintained in the target tumor only, while distribution to normal tissues was not observed, indicating that Dox and Fu concentrations below their toxic plasma concentrations should not cause significant systemic toxicity. The Dox-M/Fu-HP and Dox-M/Fu-HC drug depots described in this work showed excellent performance as chemotherapeutic delivery systems. The results reported here indicate that intratumoral injection using combination chemotherapy with Dox-M/Fu-HP or Dox-M/Fu-HC could be of translational research by enhancing the synergistic inhibitory effects of Dox and Fu on tumor growth, while reducing their systemic toxicity in cancer patients.

Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.

Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment.

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems.

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.