Burst Release Phenomenon Research Articles

New Insights on the Burst Release Kinetics of Spray-Dried PLGA Microspheres.

Spray drying is one of the leading manufacturing methods for active pharmaceutical ingredients (APIs) owing to its rapid, single-step, and cost-effective nature. It also has the capacity to generate microspheres capable of controlled release of APIs including biomolecules and vaccines. However, one of the key challenges of spray-dried formulations especially with poly(lactic-co-glycolic acid) (PLGA)-based controlled-release injectables is burst release, where a significant fraction of the API is released prematurely within a short period of time following administration, leading to detrimental impact on the performance and quality of end products. This study uses a model API, bovine serum albumin (BSA) protein, to identify the sources of burst release that may affect the kinetics and performance of long-acting injectable microsphere formulations. Spray-dried microspheres with various formulations (i.e., variable BSA/PLGA ratios) were characterized in terms of their morphology, particle size, surface area, thermal properties, moisture content, as well as chemical compositions and their distributions to investigate the impact of spray drying on the burst release phenomenon. The results suggest that a relatively high initial release (85%) observed is mainly attributed to the protein distribution close to the particle surface. Morphology analysis provided evidence that the microspheres retained their spherical structure during the burst release phase. X-ray photoelectron spectroscopy, hard X-ray photoelectron spectroscopy, and argon cluster sputtering-assisted time-of-flight secondary ion mass spectrometry analysis suggest an enrichment of PLGA on particle surfaces with buried BSA protein. The statistically significant difference in particle size and surface area between three different formulations may be responsible for an initial variation in release but did not seem to alter the overall burst release profile. Considering the suggested source of burst release, the two-fluid spray-drying method, characterized by a single liquid feed delivering a preprepared emulsion, generated matrix-type microspheres with a surface layer of PLGA, as evidenced by surface analysis. The PLGA surface layer proved to be prone to degradation and pore formation, allowing for faster diffusion of BSA out of the microspheres, resulting in a burst release. Increasing the polymer concentration did not seem to halt this process.

Core-Shell Microspheres with Encapsulated Gold Nanoparticle Carriers for Controlled Release of Anti-Cancer Drugs.

Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core-shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core-shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core-shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core-shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h.

Thermosensitive polymer prodrug nanoparticles prepared by an all-aqueous nanoprecipitation process and application to combination therapy

Despite their great versatility and ease of functionalization, most polymer-based nanocarriers intended for use in drug delivery often face serious limitations that can prevent their clinical translation, such as uncontrolled drug release and off-target toxicity, which mainly originate from the burst release phenomenon. In addition, residual solvents from the formulation process can induce toxicity, alter the physico-chemical and biological properties and can strongly impair further pharmaceutical development. To address these issues, we report polymer prodrug nanoparticles, which are prepared without organic solvents via an all-aqueous formulation process, and provide sustained drug release. This was achieved by the “drug-initiated” synthesis of well-defined copolymer prodrugs exhibiting a lower critical solution temperature (LCST) and based on the anticancer drug gemcitabine (Gem). After screening for different structural parameters, prodrugs based on amphiphilic diblock copolymers were formulated into stable nanoparticles by all-aqueous nanoprecipitation, with rather narrow particle size distribution and average diameters in the 50–80 nm range. They exhibited sustained Gem release in human serum and acetate buffer, rapid cellular uptake and significant cytotoxicity on A549 and Mia PaCa-2 cancer cells. We also demonstrated the versatility of this approach by formulating Gem-based polymer prodrug nanoparticles loaded with doxorubicin (Dox) for combination therapy. The dual-drug nanoparticles exhibited sustained release of Gem in human serum and acidic release of Dox under accelerated pathophysiological conditions. Importantly, they also induced a synergistic effect on triple-negative breast cancer line MDA-MB-231, which is a relevant cell line to this combination.

Experimental Design Modelling and Optimization of the Intercalation of Levofloxacin and Salicylic Acid into the Structure of ZnAl-LDH by Response Surface Method: in vitro Study of Release Kinetics, Antibacterial and Anti- Inflammatory Activities

In recent years, solid-state engineering has emerged as a promising method for improving the stability and potency of antibiotics and anti-inflammatory drugs. This study focuses on the design and optimization of the intercalation of levofloxacin (an antibiotic drug) and salicylic acid (an anti-inflammatory drug) into zinc-aluminium-layered double hydroxide galleries using response surface method. Release studies revealed that a burst release phenomenon was observed at the beginning of the release assay, and the pH value (in the range of 5.8-7.4) had very little influence on the levofloxacin and salicylic acid release efficiency. This indicates that zinc-aluminium-layered double hydroxide could be an effective inorganic carrier for levofloxacin and salicylic acid over a wide range of pH values. Four kinetic models were used to study the release kinetics and the drug release mechanism was also discussed. In addition, the intercalation of levofloxacin and salicylic acid into zinc-aluminium-layered double hydroxide exhibited enhanced antibacterial activity against Gram-positive Bacillus subtilis. The cell viability assay revealed non-toxic behavior of levofloxacin and salicylic acid intercalated into zinc-aluminium-layered double hydroxide against the monocyte/macrophage-like cell line.

Oilfield sustained-release tracers based on different binding forms and their controlled-release mechanism

The problem of water breakthrough in horizontal wells is serious, so it is urgent to use sustained release tracers predict and monitor the time and position of horizontal wells. In this paper, the physically bonded epoxy resin-based slow-release tracer and the chemically bonded isocyanate-linked sustained release tracer were prepared using sulfosalicylic acid as the core material. The release and key characteristics of the two sustained-release tracers at different temperatures and salinities were discussed by observing the morphological changes and release curves. The results showed that both the sustained release rate and cumulative release were positively correlated with temperature and salinity, and the epoxy resin-based sustained release tracer had obvious burst release phenomenon due to physical blending. Isocyanate-linked slow-release tracers greatly reduce burst release. The cumulative release of the isocyanate-linked slow-release tracer at 85 °C is about 1%, while the cumulative release of the epoxy resin-based slow-release tracer is about 3%. Obviously, the chemical combination is better than the physical combination. At the same time, the possible controlled release mechanism was confirmed, and the controlled release mechanism of the epoxy resin sustained-release tracer was mainly tracer diffusion. The controlled release mechanism of the isocyanate slow-release tracer is the synergistic effect of polymer degradation and tracer diffusion, and its explanation is helpful for the sustained release tracer system required for horizontal well effect monitoring.

Multi-drug delivery and osteogenic performance of β-tricalcium phosphate/alginate composite microspheres

To address the insufficiencies in the systemic research of calcium phosphate/alginate (ALG) microspheres for multi-drug delivery and bone formation, this study investigated the multi-drug release kinetics and osteogenic behaviors of β-tricalcium phosphate/ALG microspheres. The results showed that different loaded drugs exhibited an early burst release phenomenon, and the drug loading capacity decreased as the microsphere particle size decreased. In vitro cell proliferation and dead/live staining demonstrated that the microspheres had excellent cytocompatibility, and in vivo experiments demonstrated the microspheres’ exceptional ability to enhance bone regeneration.

Performance optimization of biomimetic ant-nest silver nanoparticle coatings for antibacterial and osseointegration of implant surfaces

Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.

Covalent and biodegradable chitosan-cellulose hydrogel dressing containing microspheres for drug delivery and wound healing

The purpose of this study is to prepare polysaccharide-based hydrogel dressing integrated with microspheres which has excellent self-healing ability and sustained antibacterial function for wound healing application. The hydrogel is derived from carboxymethyl chitosan (CMCS) and carboxymethyl cellulose (CMC) via the Schiff’s base reaction, without the addition of chemical catalyst. Also, the CMCS microspheres containing an antibacterial drug, e.g., tetracycline hydrochloride (TH), were prepared by an emulsion cross-linking. Parameters were optimized during the preparation experiment to improve various properties of the microspheres/hydrogel composite dressing. This gel dressing has good elasticity, when compressive strain was 0.7 mm/mm, the tangent elastic modulus was up to 1.7 MPa. Furthermore, its drug sustained release performance was significantly better than the drug directly embedded in the hydrogel. TH could sustain release stably within 12 h, without obvious burst release phenomenon. Antibacterial experiments showed that 20 mg/mL microspheres made composite dressing a better performance than control microspheres and hydrogel. Potential of the composite scaffolds was further demonstrated by culture of human adipose-derived stem cells (ASCs) in vitro. Cell culture showed that this composite hydrogel could support survival and proliferation of ASCs. These characteristics provide a potential opportunity to use this composite gel dressing in drug delivery and wound healing applications.

Comparison of Paliperidone Palmitate from Different Crystallization Processes and Effect on Formulations In Vitro and In Vivo.

The quality of active pharmaceutical ingredients (APIs) is an important factor which can affect the safety and efficacy of pharmaceuticals. This study was designed to investigate the nature of paliperidone palmitate (PP) obtained by different crystallization processes, then compare the characteristics between test formulations which prepared PP of different crystallization and reference formulations (Invega Sustenna®) in vitro and in vivo. Two different PPs, namely PP-1 and PP-2, were prepared by different crystallization methods. Contact angle, morphology, and crystallinity of the PPs were characterized. Taking the particle sizes and distribution of Invega Sustenna® as reference, test formulations were prepared by the wet milling method using either a PP-1 or PP-2 sample. Their release behavior, stability in vitro, and pharmacokinetics in vivo were subsequently investigated. The results indicated that PP-2 had a higher surface free energy (SFE). More small particles were attached to the PP-1 surface under the influence of crystallization temperature. Different crystallization processes did not change the crystal of PP, but changed the crystallinity of PP. There was no obvious difference in in vitro releases between test formulations. However, the stability and state of formulation containing PP-2 were better compared to formulations containing PP-1, indicated by differences in crystallinity and SFE. Meanwhile, pharmacokinetic in vivo results demonstrated that the pharmacokinetic profiles and parameters of formulation containing PP-2 and Invega Sustenna® tended to be consistent, but those of formulations containing PP-1 were significantly different from those of formulations containing PP-2 or Invega Sustenna®, and there was burst release phenomenon of formulations containing PP-1 in rats. PP made by different crystallization processes could induce changes in appearance, SFE, and crystallinity, and further affect the stability, state, and pharmacokinetic in vivo formulation.

Novel optimized drug delivery systems for enhancing spinal cord injury repair in rats

Effective and accurate delivery of drugs to tissue with spinal cord injury (SCI) is the key to rehabilitating neurological deficits. Sustained-release microspheres (MS) have excellent degradability and can aid in the long-term release of drugs. However, the burst release phenomenon can cause unexpected side effects. Herein, we developed and optimized an injectable poly(lactic-co-glycolic acid) (PLGA) MS loaded with melatonin(Mel), which were mixed further with Laponite hydrogels (Lap/MS@Mel, a micro-gel compound) in order to reduce the burst release of MS. Thus, these MS were able to achieve stable and prolonged Mel release, as well as synergistic Lap hydrogel in order to repair neural function in SCI by in situ injection. In clinical practice, patients with SCI have complicated conditions and significant inter-individual differences, which means that a single route of administration does not meet actual clinical needs. Thus, the nanospheres are synthesized and subsequently coated with platelet membrane (PM) in order to form PM/MS@Mel (nano-PM compound) for sustained and precision-targeted delivery of Mel intravenously in the SCI. Notably, optimized microsphere delivery systems have improved Mel regulation polarization of spinal microglial/macrophages, which can reduce loss of biomaterials due to macrophage-induced immune response during implantation of spinal cord tissue. These two new delivery systems that are based on MS provide references for the clinical treatment of SCI, according to different requirements.

Understanding the burst release phenomenon: toward designing effective nanoparticulate drug-delivery systems.

Burst release of encapsulated drug with release of a significant fraction of payload into release medium within a short period, both in vitro and in vivo, remains a challenge for translation. Such unpredictable and uncontrolled release is often undesirable, especially from the perspective of developing sustained-release formulations. Moreover, a brisk release of the payload upsets optimal release kinetics. This account strives toward understanding burst release noticed in nanocarriers and investigates its causes. Various mathematical models to explain such untimely release were also examined, including their strengths and weaknesses. Finally, the account revisits current techniques of limiting burst release from nanocarriers and prioritizes future directions that harbor potential of fruitful translation by reducing such occurrences.

Repaglinide-loaded nanostructured lipid carriers with different particle sizes for improving oral absorption: preparation, characterization, pharmacokinetics, and in situ intestinal perfusion

Repaglinide-loaded nanostructured lipid carriers (REP-NLCs) with different particle sizes were successfully designed and prepared to investigate the permeation and absorption ability by in situ single-pass intestinal perfusion (SPIP) study and pharmacokinetics. Both of the formulations prepared by solvent diffusion method exhibited a spherical shape under transmission electron microscopy (TEM) and similar zeta potential value of –11 mV. The particles size, encapsulation efficiency (EE), drug loading (DL) of REP-NLCs-Small and REP-NLCs-Large size preparations were about 79 nm and 325 nm, 96.83% and 98.60%, 4.41% and 3.05%, respectively. Besides, both REP-NLCs showed good colloidal stability and had no burst release phenomenon compared with REP-Sol. SPIP demonstrated the improved membrane permeability for NLCs compared with REP-Sol, especially NLCs-Small size preparation. The bioavailability increased sequentially in REP-Sol, REP-NLCs-Large, and REP-NLCs-Small, and the difference between each other was statistical significant. Our investigations demonstrate that NLCs with small particles size of 50–100 nm, such as 79 nm, are able to enhance absorption performance of a poorly soluble repaglinide compared with large particles size, such as 325 nm, by significantly improving the absorption in jejunum, and colon of rats and thus well improving oral bioavailability.

PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect.

Oxaliplatin (OXA) was coupled to PEGylated polyamidoamine dendrimers of fourth generation (G4-PEG@OXA) in the comparison to PEGylated ones of odd generation (G3.5-PEG@OXA). Proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy were used to confirm the successful incorporation of OXA as well as the synthesis of carrier systems. Both two types of carrier systems exhibited in sphere nanoparticle shape with size of less than 100 nm that was in the range being able to cause toxicity on cancer cells. The average drug loading efficiency (DLE) of G4-PEG@OXA was obtained at 84.63% that was higher than DLE of G3.5-PEG of 75.69%. The release kinetic of G4-PEG@OXA and G3.5-PEG@OXA did not show any burst release phenomenon while free OXA was released over 40% at the first hour. The sustainable release of OXA was achieved when it was encapsulated in these carriers, but the G4 generation liberated OXA (3.4%-6.4%) slower than G3.5 one (11.9%-22.8%). The in vitro cytotoxicities of G4-PEG@OXA were evaluated in HeLa cell lines using resazurin assay and live/dead staining test. Although the free OXA showed a rather moderate killing ability, the G4-PEG@OXA still displayed the low viability of HeLa that was better to the result of G3.5-PEG@OXA due to released OXA amount. The benefit of this system was to overcome the burst release phenomenon to minimize OXA toxicity without compromising its efficiency.

Preparation, characterization and functional evaluation of chitosan-based films with zein coatings produced by cold plasma

Chitosan-based films with zein coatings were prepared in order to modify the drug release properties. The adhesion of zein layers to the films was ensured via a cold plasma treatment. Using ciprofloxacin hydrochloride as model, the effect of cold plasma on the functional properties and structures was evaluated. The results suggest that the encapsulation efficiency, chemical composition and crystal type of ciprofloxacin hydrochloride in chitosan/drug films were not altered by cold plasma treatment, while the wettability and surface free energy displayed a notable increase. After being coated with zein, the chitosan interacted with the zein through hydrogen bonding and electrostatic interactions. The burst release phenomenon of the chitosan/drug films was prevented by the zein coating. Furthermore, the plasma treatment provided the coated film with a slower release rate within 24 h, from 72.8% to 49.3%. The enhanced coating thickness and the more compact interface structure were responsible for this improvement.

Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug Delivery.

Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment to gain a more stable material (a-LDH) in acid medium for oral administration. It demonstrated that the a-LDH had smaller crystal size, particle sizes and higher permanent charge density (σp) compared with that of the p-LDH by means of XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH and FU/p-LDH delivery systems were obtained using anion-exchange method. The in vitro 5-FU drug release studies showed that no burst release phenomenon was observed at the beginning of release tests. The in vitro 5-FU release behaviors of the delivery systems at initial pH 4.6 and 7.5 were studied which could be described by first-order and Bhaskas models. Combined with the XRD and FT-IR analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it was found that the dissolution mechanism was mainly responsible for the release behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5-FU.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4+/CD8+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.

Adsorption of nisin into layered double hydroxide nanohybrids and in-vitro controlled release

Layered double hydroxide (LDH) nanohybrid intercalated biomolecules, including oligonecluotides, genes and peptides/proteins, have attracted particular attention since they exhibit improved safety and effectiveness as successful delivery biosystems. The current study specifically investigated the adsorption of nisin peptide and precisely the control of the release of the payload. Adsorption occurred from peptide solution in contact with zinc-aluminum LDH at room temperature, looking out over the influence of the Zn2+/Al3+ ratio, the anion exchange capacity, the nature of the intercalated anion, the host matrix, and the host morphology. Higher adsorption was obtained, around 80% of the loaded nisin and successful intercalation was verified by X-ray diffraction. The in-vitro release tests of the nisin from the biohybrid formulation was held over 25days in PBS medium (0.01M, pH7,4) and showed that no burst release phenomenon occurred at the beginning step, in addition, a sustained-time release of nisin was obtained compared with the free nisin. Therefore, these preliminary results are encouraging for the development of bioprotectors based on nisin intercalated LDH and being implemented in the food and medical industries.

A controlled release strategy of antifouling agent in coating based on intercalated layered double hydroxides

A controlled release method of antifouling agent was demonstrated via the model coating which was fabricated by sodium paeonolsilate (PAS) intercalated into Zn2Al Layered Double hydroxides (LDH) and then dispersed in the mixture of acrylic resin and colophony with weight ratio of 2:1. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of Zn2Al-LDH. Some larger particles of Zn2Al-PAS-LDH composite in the coating were observed owing to its aggregation, which was revealed by Laser scanning confocal microscope (LSCM). The release tests of the Zn2Al-PAS-LDH coating in 3.5% NaCl solution showed that no burst release phenomenon occurred at the beginning stage and a slower release rate of PAS (0.54ppm/d) was obtained compared with the pristine PAS coating (1.06ppm/d), exhibiting its preferable controlled release behavior. The adhesion experiment using Ulva zoospores indicated that Zn2Al-PAS-LDH composite obviously increases the utilization rate of PAS owing to its controlling release property. Therefore, the present work provided a useful strategy to decrease the waste of antifouling agent and prolong the lifetime of antifouling coatings.

Nano-Cu/Low-Density Polyethylene Composites: Structure and Control Release of Cupric Ions

In recent years a new type of intrauterine device (nanoCu/LDPE composites) has been concerned by a lot of scholars for its short release time, high bioavailability and good biocompatibility. In this study nanoCu/low-density polyethylene composites were prepared by extruding mixtures of pure LDPE and nanoCu using melt-blending method, the release rate of cupric ions (Cu2+) was measured in simulated uterine fluid. The non-isothermal crystallization behavior and thermal stability of the composites before and after immersion were studied by differential scanning calorimetry (DSC) and thermogravimetric analyzer (TG). The results showed that Composites effectively shorten the time of the copper ion "burst release" , the burst release phenomenon of Cu2+ occurred during the first five days after immersion , and then tend to stable . By immersion the crystallinity of composites increased, and the thermal stability decreased.

Preparation and in vitro evaluation of 5-flourouracil loaded magnetite-zeolite nanocomposite (5-FU-MZNC) for cancer drug delivery applications.

In this work, super paramagnetic magnetite nanoparticles were synthesized onto/into zeolite, then loaded with anti-cancer drug 5-fluorouracil (5-FU). The physical properties of the prepared nanocomposite and drug loaded nanocomposite were characterized using different techniques. The drug loading and releasing behavior of the magnetic nanocarrier was investigated and the drug-loaded nanoparticles exhibited a sustained release of drug without any burst release phenomenon. Furthermore, 5-FU loaded MZNC were evaluated for its biological characteristics. The functional 5-FU-MZNC has been triggered intra-cellular release of the cancer therapeutic agent 5-fluorouracil (5-FU). Cytotoxic effects of 5-FU loaded MZNC on human gastric carcinoma (AGS) cells were determined by real time cell analysis and colorimetric WST-1 cell viability assay. Apoptosis of cells was further investigated by Annexin-V staining which indicates the loss of cell membrane integrity. According to our results, 5-FU-MZNC showed a concentration-dependent cell proliferation inhibitory function against AGS cells. Morphologic and apoptotic images were consistent with the cytotoxicity results. In conclusion, 5-FU loaded MZNC efficiently inhibit the proliferation of AGS cells in vitro through apoptotic mechanisms, and may be a beneficial agent against cancer, however further animal study is still required.