Initial Burst Release Of Drug Research Articles

The Alginate Layer for Improving Doxorubicin Release and Radiolabeling Stability of Chitosan Hydrogels.

Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated. Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37°C for 12days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37°C for 12days. Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5% for 0.25, 0.50, and 1.00mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the released Dox for 12days was decreased to 47.6 ± 1.4, 51.1 ± 1.4, and 57.5 ± 1.6% for 0.25, 0.50, and 1.00mg Dox used, respectively. The radiolabeling stability of DI-CSH in human serum was improved by alginate layer. The formation of alginate layer on the surface of the DI-CSH is useful for improving the drug release behavior and radiolabeling stability.

Optimization and Characterization of Artesunate‐Loaded Chitosan‐Decorated Poly(D,L‐lactide‐co‐glycolide) Acid Nanoparticles

The aim of this study was to optimize the formulation of artesunate‐loaded chitosan‐ (CS‐) decorated poly(D,L‐lactide‐co‐glycolide) acid (PLGA) nanoparticles as well as evaluate their characteristics. CS‐to‐PLGA mass ratio, pH of CS solution, and experimental temperature were optimized using response surface methodology to understand their effects on size and zeta potential of nanoparticles. The optimized formulation showed the close agreement between predicted and experimental values (all bias below 5%). The presence of CS was confirmed by positive surface charge and Fourier transform infrared spectroscopy. A spherical‐like shape of particles was observed in range of small size around 190 nm. This CS layer restricted initial burst release of drug from carriers in phosphate buffer of pH 6.8. In addition, CS‐coated NPs enhanced the intracellular uptake, in vitro cytotoxicity, and apoptosis‐induced nuclei behaviors compared with CS‐uncoated NPs as well as free drug in MCF‐7 and A549 cancer cells.

Calcium phosphate bone cements for local vancomycin delivery.

Among calcium phosphate biomaterials, calcium phosphate bone cements (CPCs) have attracted increased attention because of their ability of self-setting in vivo and injectability, opening the new opportunities for minimally invasive surgical procedures. However, any surgical procedure carries potential inflammation and bone infection risks, which could be prevented combining CPC with anti-inflammatory drugs, thus overcoming the disadvantages of systemic antibiotic therapy and controlling the initial burst and total release of active ingredient. Within the current study α-tricalcium phosphate based CPCs were prepared and it was found that decreasing the solid to liquid phase ratio from 1.89g/ml to 1.23g/ml, initial burst release of vancomycin within the first 24h increased from 40.0±2.1% up to 57.8±1.2% and intrinsic properties of CPC were changed. CPC modification with vancomycin loaded poly(lactic acid) (PLA) microcapsules decreased the initial burst release of drug down to 7.7±0.6%, while only 30.4±1.3% of drug was transferred into the dissolution medium within 43days, compared to pure vancomycin loaded CPC, where 100% drug release was observed already after 12days. During the current research a new approach was found in order to increase the drug bioavailability. Modification of CPC with novel PLA/vancomycin microcapsules loaded and coated with nanosized hydroxyapatite resulted in 85.3±3.1% of vancomycin release within 43days.

Hyaluronic acid/chitosan nanoparticles for delivery of curcuminoid and its in vitro evaluation in glioma cells

The aim of this work was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan (HA/CS) as carriers for water-insoluble curcuminoid (CUR) and explore in vitro performance against brain glioma cells. PENPs were observed to be affected by the order of addition, mass ratios and initial concentrations of the HA/CS, pH and ionic strength. PENPs remained stable over a temperature range of 5–-55(C. CUR was successfully encapsulated into the PENPs. CUR-PENPs showed spherical shape with a mean diameter of 207nm and positive charge of 25.37mV. High encapsulation efficiency (89.9%) and drug loading (6.5%) was achieved. Drug release studies revealed initial burst release of drug from the PENPs up to 4h followed by sustained release pattern. DSC thermograms and XRD patterns showed that CUR was encapsulated inside the PENPs in a molecular or amorphous state. Compared with CUR-solution, CUR-PENPs showed stronger dose dependent cytotoxicity against C6 glioma cells and higher performance in uptake efficiency in C6 cells. Cellular uptake of CUR-PENPs was found to be governed by multi-mechanism in C6 cells, involving active endocytosis, macropinocytosis, clathrin-, caveolae-, and CD44-mediated endocytosis. In conclusion, CUR-PENPs might be a promising carrier for therapy of brain gliomas.

A novel multiple drug release system in vitro based on adjusting swelling core of emulsion electrospun nanofibers with core–sheath structure

We have developed a novel drug delivery system with the swelling core for differential release of multiple drugs by emulsion electrospinning, in which the aqueous phase is composed of polyvinyl alcohol and the oil phase consists of poly(ε-caprolactone). The microscopy images indicate that the W/O nanofibers with swelling core structure are successfully prepared and the model drugs, Rhodamine B and bovine serum albumin, were encapsulated in the fibers. In vitro drug release study demonstrated that this core–sheath structure could significantly alleviate the initial drug burst release and provided a differential diffusion pathway to release. It could be found that the postponement of the maximum accumulated release of bovine serum albumin was found due to the presence of sodium citrate and different types of polyvinyl alcohol. This study would provide a basis for optimization of encapsulation conditions to control the release of multiple agents and ultimately be applied in cancer chemotherapy.

Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route

Intranasal drug administration is receiving increased attention as a delivery method for bypassing the blood–brain barrier and rapidly targeting therapeutics to the CNS. However, rapid mucociliary clearance in the nasal cavity is a major hurdle. The purpose of this study was to evaluate the effect of mucoadhesive polymers in enhancing the delivery of nimodipine microemulsion to the brain via the intranasal route. The optimized mucoadhesive microemulsion was characterized, and the in vitro drug release and in vivo nasal absorption of drug from the new formulation were evaluated in rats. The optimized formulation consisted of Capmul MCM as oil, Labrasol as surfactant, and Transcutol P as co-surfactant, with a particle size of 250nm and zeta potential value of −15mV. In vitro and ex vivo permeation studies showed an initial burst of drug release at 30min and sustained release up to 6h, attributable to the presence of free drug entrapped in the mucoadhesive layer. In vivo pharmacokinetic studies in rats showed that the use of the mucoadhesive microemulsion enhanced brain and plasma concentrations of nimodipine. These results suggest that incorporation of a mucoadhesive agent in a microemulsion intranasal delivery system can increase the retention time of the formulation and enhance brain delivery of drugs.

Controlled drug release from a novel drug carrier of calcium polyphosphate/chitosan/aldehyde alginate scaffolds containing chitosan microspheres

Initial burst release of drugs is a major shortcoming which needs to be addressed in treating osteomyelitis by using drug delivery systems (DDS). The aim of this study was to develop a novel DDS for reducing initial burst release based on the combination of chitosan (CS) microspheres and calcium polyphosphate/chitosan/aldehyde alginate (CPP/CS/ADA) composite scaffolds. CS microspheres and CPP/CS/ADA composite scaffolds were characterized by FTIR spectroscopy, a laser particle size analyzer and SEM in order to reveal their composition, size distribution and surface morphology. Tetracycline hydrochloride (TC), as a model drug in the study, was encapsulated in CS microspheres, which further combined with CPP/CS/ADA composite scaffolds to form new DDS. Then the in vitro drug release was studied in detail. The kinetics of the drug release was also systematically studied. The results indicate that this new microspheres/scaffold compound system has a promising potential to reduce initial drug burst release effectively and prolong drug release time even for 30 days.

The Anti-Melanoma Efficiency of the Intratumoral Injection of Cucurbitacin-Loaded Sustained-Release Carriers: A PLGA Particle System

A dilemma for current cancer therapy is surgical injury in addition to the toxicities and inefficiencies of systemic chemotherapy. Meanwhile, localized therapies have become a noticeable strategy. In this study, Cucurbitacin (Cuc)-loaded poly(lactic-co-glycolic acid) particles of different sizes (about 50 μm, 5 μm, and 270 nm, respectively) were prepared as the sustained-release system for intratumoral injection, and their physicochemical properties, in vitro cytotoxicity, particles-cells interactions, pharmacokinetics, and pharmacodynamics were systemically investigated for the first time. The results of cytotoxicity experiments and pharmacokinetic/pharmacodynamic studies indicated that the release patterns of the particles would strongly affect the biological efficiency not only at the cell level but also in two types of animal models. Cuc raw material and nanoparticles showed higher initial burst release in vitro, and higher drug concentration in tumor and plasma. Large particles (about 50 μm) showed lower initial burst and slow drug release, which would not supply enough amount of drug to inhibit the cancer cell growth during the whole treatment period. Particles with mean diameter of about 5 μm performed the best anti-melanoma efficiency both in vitro and in vivo. The release patterns, instead of the particles-cells interactions, would be the key factors to affect the biological effects of the particulate system for intratumoral injection.

Design and Pharmaceutical Evaluation of a Nano-Enabled Crosslinked Multipolymeric Scaffold for Prolonged Intracranial Release of Zidovudine

Nanomedicine explores and allows for the development of drug delivery devices with superior drug uptake, controlled release and fewer drug side-effects. This study explored the use of nanosystems to formulate an implantable drug delivery device capable of sustained zidovudine release over a prolonged period. Pectin and alginate nanoparticles were prepared by applying a salting out and controlled gelification approach, respectively. The nanoparticles were characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS) and were further evaluated for zidovudine (AZT) entrapment efficiency. Multipolymeric scaffolds were prepared by crosslinking carboxymethyl cellulose, polyethylene oxide and epsilon caprolactone for entrapment of zidovudine-loaded alginate nanoparticles to impart enhanced controlled release of zidovudine over the time period. Swelling and textural analysis were conducted on the scaffolds. Prepared scaffolds were treated with hydrochloric acid (HCl) to reduce the swelling of matrix in the hydrated environment thereby further controlling the drug release. Drug release studies in phosphate buffered saline (pH 7.4, 37°C) were undertaken on both zidovudine-loaded nanoparticles and native scaffolds containing alginate nanoparticles. A higher AZT entrapment efficiency was observed in alginate nanoparticles. Biphasic release was observed with both nanoparticle formulations, exhibiting an initial burst release of drug within hours of exposure to PBS, followed by a constant release rate of AZT over the remaining 30 days of nanoparticle analysis. Exposure of the scaffolds to HCl served to reduce the drug release rate from the entrapped alginate nanoparticles and extended the AZT release up to 30 days. The crosslinked multipolymeric scaffold loaded with alginate nanoparticles and treated with 1% HCl showed the potential for prolonged delivery of zidovudine over a period of 30 days and therefore may be a potential candidate for use as an implantable device in treating Aids Dementia Complex.

Role of 3-aminopropyltriethoxysilane in the preparation of mesoporous silica nanoparticles for ibuprofen delivery: Effect on physicochemical properties

The development of mesoporous silica nanoparticle-based platforms for a controlled drug delivery was studied. Mesoporous silica nanoparticles (MSN) was synthesized and modified with 3-aminopropyltriethoxysilane (APTES) using co-condensation (MSNco) and post-grafting (MSNpost) methods. X-ray diffraction (XRD) and transmission electron microscopy (TEM) data confirmed the formation of ordered mesostructured silica nanoparticles. The performance of MSNs was then tested on an ibuprofen immobilization and release. The results revealed that unmodified MSN demonstrated the best immobilization rate and capacity of ibuprofen (98%), MSNpost exhibited higher ibuprofen adsorption (78%) as compared to MSNco (71%), suggesting the modification method is not the dominant factor for the adsorption studied. In fact, according to the FT-IR results, the silanol groups density was found to be the contributing factor that affected the adsorption. The in vitro drug release was also investigated with simulated biological fluids. In 20h, MSNco showed the fastest release of ibuprofen (100%), followed by MSN (50%) and MSNpost (38%). Both pore size and amine groups influenced the rate of the release process. From the results, MSN and MSNpost is suggested to have suitable features for slow drug release which provides constant release over a defined period to avoid repeated administration. While MSNco could be best employed as a fast release system that provides initial burst of drug release to achieve rapid and maximum relief.

Coaxial electrospun zein nanofibrous membrane for sustained release

Zein nanofibrous membranes for sustained release have been prepared by coaxial electrospinning. Core-sheath structure has been successfully fabricated using zein as both the core and sheath component. Impact of solvent and solution concentration on the morphology of the resulting fibers was investigated. Allyltriphenylphosphonium bromide was used as a model drug to test the sustained release effect. The sustained release profile and the antimicrobial activity of the resulting membranes were investigated and compared with that of the single fluid electrospinning of zein/drug blended membrane. The ratio of the inner and outer feeding rates was found to influence the encapsulation of drugs, and in turn affect the sustained release effect of the resulting membranes. The coaxial electrospinning membrane can remarkably suppress the initial burst release of drugs by giving a releasing amount of 15% in the first 1 h when the inner/outer ratio was larger than 1:2. This drug-loaded zein membrane with preferable sustained release effect can be applied in many fields such as wound healing and packaging sector.

Formulation and in-vitro evaluation of moxifloxacin loaded crosslinked chitosan films for the treatment of periodontitis

AimThe purpose of the present work was to develop a local drug delivery system of moxifloxacin loaded crosslinked chitosan films using sodium citrate as a crosslinking agent with different concentrations and crosslinking time. MethodsThe films were prepared using solvent casting technique. The formulated films were evaluated for physicochemical parameters like FT-IR, DSC, thickness, weight variation, content uniformity, surface pH and release kinetics. ResultsIR and DSC studies indicated that there is no interaction between the drug and excipients. The drug loaded chitosan films were flexible, possessed good tensile strength and demonstrated satisfactory physicochemical characteristics. Although the films showed an initial burst release of drug, the release was sustained for up to 15 days. From the obtained results F6 formulation is optimized one among all the formulations. ConclusionThe present work suggests that the controlled release Moxifloxacin loaded Chitosan films crosslinked with sodium citrate have a remarkable role in the local therapy of periodontitis.

Polydopamine-Based Surface Modification for the Development of Peritumorally Activatable Nanoparticles

To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs). PLGA NPs were modified with TAT peptide (PLGA-pDA-TAT NPs) or dual-modified with TAT peptide and a conjugate of PEG and MMP-substrate peptide (peritumorally activatable NPs, PANPs) via dopamine polymerization. Cellular uptake of fluorescently labeled NPs was observed with or without a pre-treatment of MMP-2 by confocal microscopy and flow cytometry. NPs loaded with paclitaxel (PTX) were tested against SKOV-3 ovarian cancer cells to evaluate the contribution of surface modification to cellular delivery of PTX. While the size and morphology did not significantly change due to the modification, NPs modified with dopamine polymerization were recognized by their dark color. TAT-containing NPs (PLGA-pDA-TAT NPs and PANPs) showed changes in surface charge, indicative of effective conjugation of TAT peptide on the surface. PLGA-pDA-TAT NPs and MMP-2-pre-treated PANPs showed relatively good cellular uptake compared to PLGA NPs, MMP-2-non-treated PANPs, and NPs with non-cleavable PEG. After 3 h treatment with cells, PTX loaded in cell-interactive NPs showed greater toxicity than non-interactive ones as the former could enter cells during the incubation period. However, due to the initial burst drug release, the difference was not as clear as microscopic observation. PEGylated polymeric NPs that could expose cell-interactive surface in response to MMP-2 were successfully created by dual modification of PLGA NPs using dopamine polymerization.

Microfluidic synthesis of alginate 6-methoxyenthylamino numonafide (MEAN)– eluting microspheres for catheter-directed delivery to liver tumors

Purpose Amonafide has demonstrated potent efficacy to treat a broad range of solid tumors including HCC but clinical application has been limited due to severe toxicities. These toxicities have been mitigated with a new metabolically stable drug, 6-methoxyenthylamino numonafide (MEAN). Local transcatheter delivery to liver tumors using drug-eluting beads could also reduce toxicity of this drug. We aimed to test the hypothesis that microfluidic techniques can be used to synthesize MEAN-eluting alginate microspheres. Materials and Methods Microspheres were produced via custom-made microfluidic set-up, consisting of microfluidic chip, syringe pumps and optical microscope. Continuous synthesis of MEAN loaded magnetic alginate microspheres was performed by controlling the flow rate of oil (Qo) phase (N’-hexadecane and span 80) and aqueous (Qa) phase (alginate, magnetic clusters, and MEAN) constituents. Fluorescence measurements (λex=445 nm and λem=550 nm) were used to quantify MEAN elution rates from these alginate spheres into release media in triplicate tests. Imaging of these magnetic microspheres was performed using a 7T MR scanner (Bruker). Results Microfluidic methods effectively produced hydrophilic, deformable, and non-aggregated biodegradable alginate microspheres with a mono size range of 30~70 um (size dependent upon channel size and flow rates). Encapsulation of MEAN and magnetic clusters in the alginate microspheres was confirmed with fluorescent microscopy. The magnetic clusters embedded into the alginate matrix controlled drug release rates and prevented initial burst drug release. Strong T2-weighted image contrast was achieved due to the magnetic clusters within these microsphere drug carriers. Conclusion Microfluidic methods effectively produced MEAN-eluting magnetic alginate microspheres. These microspheres offer the benefits of controlled drug release and visibility with MR imaging. Future animal studies should verify efficacy of selective transcatheter delivery to liver tumors.

Development of meloxicam in situ implant formulation by quality by design principle

Objective: The focus of this study was to develop and optimize in situ implant formulation of meloxicam by quality by design (QbD) principle for long-term management of musculoskeletal inflammatory disorders.Methods: The formulation was optimized by Box–Behnken design with polylactide-co-glycolide (PLGA) level (X1), N-methyl pyrrolidone level (X2) and PLGA intrinsic viscosity (X3) as the independent variables and initial burst release of drug (Y1), cumulative release (Y2), and dissolution efficiency (Y3) as the dependent variables. The formulation was physicochemically characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD). Pharmacokinetic studies of the optimized formulation were performed on Sprague--Dawley rats.Results: Y1 was significantly affected by X2 and X3. Y2 was affected by X1 and X3 while Y3 was affected by all three independent variables employed in the formulations. Responses for the optimized formulation were in close agreement with the values predicted by the model. SEM photomicrographs indicated uniform gel formulation. No chemical interaction between the components of formulation was observed by FT-IR and meloxicam was found to be present in the amorphous form in the gel matrix as revealed by PXRD. The maximum plasma concentration (Cmax), time to achieve Cmax and area under plasma concentration curve were significantly different from those of the solution formulation used as the control. Plasma concentration of meloxicam was maintained above its IC50 concentration required for COX-2 inhibition for 23 days.Conclusion: Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.

Comparative release profile of sustained release matrix tablets of verapamil HCl

Introduction:Verapamil hydrochloride (VH) is a calcium channel blocking agent used in the treatment of hypertension, cardiac arrhythmia and angina pectoris. The short half-life and high frequency of administration of VH makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of verapamil hydrochloride (VH) using ethyl cellulose, methyl cellulose, Eudragit RS 100, hydroxypropyl methylcellulose and carboxymethyl cellulose and to evaluate the drug release kinetics.Materials and Methods:In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method using avicel PH 101 and magnesium stearate as binder and lubricant, respectively.Results:The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. Furthermore, to minimize the initial burst drug release, batches were coated by using Eudragit RS100 polymer. After coating the tablets, a better release profile of the formulated tablets was expected and the release rate of the drug was compared with the marketed SR tablet of VH.Conclusion:The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.

Formulation development and optimization of bilayer tablets of aceclofenac

Objective: The objective of the present study was to develop bilayer tablets of aceclofenac that are characterized by initial burst drug release followed by sustained release of drug.Methods: The fast-release layer of the bilayer tablet was formulated using microcrystaline cellulose (MCC) and HPMC K4M. The amount of HPMC E4M (X1) and MCC (X2) was used as independent variables for optimization of sustained release formulation applying 32 factorial design. Three dependent variables were considered: percentage of aceclofenac release at 1 h, percentage of aceclofenac release at 12 h, and time to release 50% of drug (t50%). The composition of optimum formulation of sustained release tablets were employed to formulate double layer tablets.Results: The results indicate that X1 and X2 significantly affected the release properties of aceclofenac from sustained release formulation. The double layer tablets containing fast-release layer showed an initial burst drug release of more than 30% of its drug content during first 1 h followed by sustained release of the drug for a period of 24 h.Conclusion: The double layer tablets for aceclofenac can be successfully employed as once-a-day oral-controlled release drug delivery system characterized by initial burst release of aceclofenac for providing the loading dose of drug.

Huperzine A–phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release

The huperzine A–phospholipid complex loaded biodegradable thermosensitive PLGA–PEG–PLGA polymer gel was studied as injectable implant system for controlled release of huperzine-A (HA). First, HA molecules were successfully incorporated into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A–soybean phosphatidylcholine complexes (HA–SPC), which was proved by FT-IR, DSC, XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and electrostatic interaction between HA and SP molecules play an important role in the formation of HA–SPC. Secondly, the HA–SPC was loaded into biodegradable PLGA–PEG–PLGA thermosensitive gel as injectable implant material to control the release of HA. The in vitro and in vivo drug release behaviors of the prepared products were studied. The in vitro release studies demonstrated that the HA–SPC-loaded gel significantly reduced the initial burst of drug release and extended the release period to about 2 weeks. The in vivo pharmacokinetics study of HA–SPC-loaded gel in rabbits showed that plasma concentration of HA (2.54–0.15ng/mL) was detected for nearly 2 weeks from delivery systems upon single subcutaneous injection. What's more, the in vitro release pattern correlated well with the in vivo pharmacokinetics profile. The present study indicates that HA–SPC loaded PLGA–PEG–PLGA thermal gel may be an attractive candidate vehicle for controlled HA release.

Paclitaxel-incorporated nanoparticles of hydrophobized polysaccharide and their antitumor activity

The aim of this study was to characterize paclitaxel-incorporated polysaccharide nanoparticles and evaluate their antitumor activity in vitro and in vivo. Pullulan was hydrophobically modified using acetic anhydride to make the paclitaxel-incorporated nanoparticles. Pullulan acetate (PA) was used to encapsulate paclitaxel using the nanoprecipitation method. The particles had spherical shapes under electron microscopy with sizes <100nm. The sizes of paclitaxel-incorporated nanoparticles increased to >100nm, and higher drug feeding induced higher particle size and drug content. Initial drug burst release was observed until 2 days and then the drug was continuously released over 1 week. Intrinsic cytotoxicity of empty PA nanoparticles was tested with RAW264.7 macrophage cells for biocompatibilty. The viability of RAW264.7 cells was >93% at all concentrations of empty PA nanoparticles, indicating that the PA nanoparticles are not acutely cytotoxic to normal human cells. The nanoparticles showed lower antitumor activity in vitro against HCT116 human colon carcinoma cells than that of paclitaxel itself, indicating the sustained release properties of nanoparticles. An in vivo study using HCT116 human colon carcinoma-bearing mice showed that paclitaxel-incorporated PA nanoparticles reduced tumor growth more than that of paclitaxel itself. These results indicate that PA paclitaxel-incorporated nanoparticles are a promising candidate for antitumor drug delivery.

The Effect of Temozolomide/Poly(lactide-co-glycolide) (PLGA)/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior

In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.