Development of α-tocopherol surface-modified targeted delivery of 5-fluorouracil-loaded poly-D, L-lactic-co-glycolic acid nanoparticles against oral squamous cell carcinoma

Objective: The aim of the study to develop surface modified targeted moiety α-tocopherol (α-t) encapsulated with 5-fluorouracil (5-FU)-poly-D, L-lactic-co-glycolic acid nanoparticles (PLGA NPs) toward the anticancer activity against oral squamous cell carcinoma (OSCC). Materials and Methods: 5-FU was conjugated with the polymer, PLGA by ionic cross-linking and α-tocopherol use as a functionalized surface moiety. Characterization, drug entrapment efficiency, and in-vitro drug release system were optimized at different pH 7.4 and pH 4.5. The in-vitro cell was performed to optimize the anticancer activity through MTT assay and apoptotic staining assay was also performed by flow cytometry to evaluate the cellular apoptotic activity and cellular uptake. Results: The particle size was distributed within an average range of 145–162 nm, the polydispersity index values lie 0.16–0.30, and the surface charge was at the negative side, –17mV to –23mV. The in vitro drug release system showed more sympathetic situation at pH 7.4 as compared to pH 4.5, for targeted NPs, approximately 86% and 69%, respectively. The non-targeted 5-FU-PLGA NPs showed drug release of 83% and 64% at pH 7.4 and 4.5 subsequently. In vitro anticancer activity confirmed the intense inhibition by α-t-FU-PLGA NPs of 79.98% after 96 h treatment of SCC15 cells and confirmed the steady-state inhibition of 83.74% after 160 h incubation in comparison to 5-FU-PLGA NPs. Subsequently, the early apoptosis, 27.98%, and 16.45%, and late apoptosis, 47.29%, and 32.57%, suggested the higher apoptosis rate in targeted NPs against OSCC. Conclusions: The surface modified α-t-FU-PLGA NP was treated over SCC15 cells, and the oral cancer cells have shown the high intensity of cellular uptake, which confirmed that the target moiety has successfully invaded over the surface of cancer cells and shown advanced targeted delivery against OSCC

Growth Behavior of Endothelial Cells According to Electrospun poly(D,L-Lactic-Co-Glycolic Acid) Fiber Diameter as a Tissue Engineering Scaffold

Investigating the effect of electrospun fiber diameter on endothelial cell proliferation provides an important guidance for the design of a fabric scaffold. In this study, we prepared biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) fibrous nonwoven mats with different fiber diameters ranged from 200 nm to 5 µm using the electrospinning technique. To control the fiber diameters of PLGA mats, 4 mixture solvents [hexafluoro-2-propanol, 2,2,2,-trifluoroethanol:dimethylformamide (9:1), 2,2,2,-trifluoroethanol:hexafluoro-2-propanol (9:1), chloroform] were used. Average diameters were 200 nm, 600 nm, 1.5 µm, and 5.0 µm, respectively. Stereoscopic structure and spatial characterization of fibrous PLGA mats were analyzed using atomic force microscopy and a porosimeter. The mechanical properties of PLGA mats were analyzed using a universal testing machine. The spreading behavior and infiltration of endothelial cells on PLGA mats were visualized by field emission scanning electron microscopy and hematoxylin and eosin staining. Cell proliferation on different PLGA fibers with different diameters was quantified using the MTT assay. Cells on 200 nm diameter PLGA mats showed rapid attachment and spreading. However, the cells did not penetrate the PLGA mat. Cells cultured on 600 nm and 1.5 µm diameter fibers could infiltrate the pores and cell proliferation was dramatically increased after 14 days. Secreted prostacyclin from endothelial cells on each mat was measured to examine the ability to inhibit platelet activation. This basic study on cell proliferation and fiber diameter with physical characterization provides a foundation for studies examining nonwoven fibrous PLGA mats as a tissue engineering scaffold.

Evaluation on the bone regenerative capacity of hyaluronic acid applied poly (D,L-lactic-co-glycolic acid) membranes in rabbit calvarial defect / 대한치과보철학회지

PURPOSE: The objective of the present study was to histologically evaluate durability and bone regeneration capacity of new synthetic membranes in comparison to clinically available collagen membrane. MATERIAL AND METHODS: To the skulls of 12 rabbits, we created 4 bone defects of 6 mm in diameter on each of them. Each of defects were covered with at least one of 5 membranes: No membrane, Collagen (Ossix(TM)), PLGA, HA-coated-PLGA and HA-PLGA/PLGA. After 4, 8, 12 weeks, we cut the skulls and dyed with H-E. And then, the histologic observation was done. RESULTS: In current study, the control group which did not use the membrane showed bone regeneration at 12 weeks and covered the bone defect partially. New bones were formed through the underneath of endocranium, and the upper defect was filled with connective tissues and fats. Collagen membrane (Ossix(TM)) showed new bones after 4 weeks, and they were formed through the membrane which maintained until 12 weeks. PLGA, HA-coated-PLGA, HA-PLGA/PLGA showed bone regeneration after 4 weeks and after 8 weeks, they mostly filled defects. At 12 weeks, we could find new bones and previous bones almost look alike and also, they united well. Membranes were unnoticeable after 4 weeks and were absorbed. CONCLUSION: Bone formation and maturation of PLGA, HA-coated-PLGA and HA-PLGA/PLGA were faster than the control group. They showed no difference on the application of HA and after 4 weeks, they were absorbed.

Study on microneedle technique in enhancement of transdermal nanoparticle delivery / 第二军医大学学报

Objective: To investigate the microneedle technique in enhancement of transdermal nanoparticle delivery and the distribution of poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles in the skin and the transdermal microconduits. Methods: Double fluorescent PLGA nanoparticles were used to show the transdermal transport process. Franz diffusion cell was used for the transdermal study. The nanoparticle suspension was added to the donor chamber. The hairless mouse skin in the microneedle group was treated by microneedle technique and that in the control group was not treated. Penetration of nanoparticles was visualized by confocal laser scanning microscopy (CLSM). Distribution of nanoparticle diameter was quantified by HPLC. Results: The CLSM images revealed that the nanoparticles were delivered into the microconduits created by microneedles and entered the epidermis and the dermis. The quantitative results showed that no nanoparticles reached the receptor compartment 48 h after addition of the nanoparticles in both groups. In microneedle group the nanoparticle amount was 125.99 μg/cm2 in the epidermis and 55.31 μg/cm2 in the dermis, with the total amount in the skin being 181.30 μg/cm2; in the the control group, the nanoparticle amount was 42.15 μg/cm2 in the epidermis and 32.76 μg/cm2 in the dermis, with the total amount in the skin being 74.91 μg/cm2. Microneedle technique significantly increased the amount of nanoparticles entering the skin (P<0.01), and the amount in the epidermis was significantly more than that in the dermis (P<0.01). Conclusion: Our results suggest that microneedles can enhance the intradermal PLGA nanoparticle delivery, and the nanoparticles deposit in the skin to achieve sustainable drug release, which is beneficial for topical drug administration.

Preparation and characterization of magnetic poly D,L-lactide-co-gylcolide phenylarsine oxide nanoparticles / 第二军医大学学报

Objective: To study the preparation technique for magnetic poly D, L-lactide-co-glycolide phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to characterize the resultant product. Methods: M-PLGA-PAO-NPs were prepared by using emulsion-evaporation process. The morphology of the prepared nanoparticles were observed by transmission electron microscope and the magnetism of the particles was determined by vibrating sample magnetometer. Meanwhile, we also evaluated the mean diameter, encapsulation ratio, and drug loading rate of the particles. Results: The nanoparticles had a regular spherical surface, with 80% of them having a diameter of 140-500 nm. We also found that the drug loading rate of the particles was 3.2 % and the mean encapsulation ratio was 34.2%. The drug had satisfactory magnetic property. Conclusion: Our method can obtain M-PLGA-PAO-NP with satisfactory quality, it is simple-to-use and the prepared particles can meet the requirement of pharmaceutics..

Low Frequency Ultrasound Triggering Drug Release from Improved PLGA Microcapsules in Vitro / 中国康复理论与实践

@# Objective To study the effect of low frequency on drug release from improved PLGA microcapsules, and investigate the possibility of utilizing PLGA microcapsules as the carrier of ultrasound targeted drug delivery system to deliver drug into brain. Methods Doxorubicin loaded poly (D,L lactic-co-glycolic acid) (PLGA) microcapsules were prepared via double emulsion solvent evaporate method and coated with either chitosan or gelatin. In vitro drug release profile and the drug release rate under the exposure of low frequency pulsed ultrasound (25 kHz) and continuous wave ultrasound (35.1 kHz) were assayed. Results The coating with chitosan or gelatin can depress the burst of drug release. The drug release rate from uncoated and chitosan-coated microcapsules did not changed with the exposure of ultrasound, and the rate of gelatin-coated microcapsules did increased. The effect of pulsed ultrasound was stronger than that of continuous ultrasound. Conclusion The drug release from gelatin-coated PLGA microcapsules can be controlled and triggered by 25 kHz pulsed ultrasound, which may be a potent carrier of targeting drugs into brain.

Preparation and characterization of magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles / 第二军医大学学报

Objective:To study the preparation technique for magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to characterize the resultant product. Methods: M-PLGA-PAO-NPs were prepared by using emulsion-evaporation process. The morphology of the prepared nanoparticles were observed by transmission electron microscope and the magnetism of the particles was determined by vibrating sample magnetometer. Meanwhile, we also evaluated the mean diameter, encapsulation ratio, and drug loading rate of the particles. Results: The nanoparticles had a regular spherical surface, with 80% of them having a diameter of 140-500 nm. We also found that the drug loading rate of the particles was 3.2% and the mean encapsulation ratio was 34.2%. The drug had satisfactory magnetic property. Conclusion: Our method can obtain M-PLGA-PAO-NP with satisfactory quality, it is simple-to-use and the prepared particles can meet the requirement of pharmaceutics.

Immunotherapy with Recombinant House Dust Mite Group 2 Allergen Vaccine Inhibits Allergic Airway Inflammation in Mice / 中国寄生虫学与寄生虫病杂志

Objective To investigate the efficacy and mechanism of subcutaneously given recombinant Der p 2 entrapped PLGA nanoparticles(DEPN) on mouse model with allergic airway inflammation.Methods 40 BALB/c mice were randomly divided into 5 groups,group A(normal control) were treated with saline(100 ?l) all the time,groups B,C,D and E were sensitized intraperitoneally with crude dust mite extracts(10 ?g) and then subcutaneously treated respectively with PBS(100 ?l),2 mg empty PLGA(EP),100 ?g rDer p 2,and 2 mg DEPN(loaded with 100 ?g rDer p 2) for 3 times,once per day,followed by intranasal challenge of 50 ?g rDer p 2.One day post challenge,mice were sacrificed and bronchoalveolar lavage fluid(BALF) was collected.Number of the total cells and eosinophils was determined,and airway inflammation and mucus secretion were analyzed by haematoxylin and eosin(H&E) staining and periodic acid-Schiff(PAS) staining.Level of cytokines in the supernatant of splenocyte culture was assayed by ELISA.Level of rDer p 2 specific IgG2a and IgE in the sera was determined by ELISA.Results The lung histology showed development of eosinophil infiltration in the airway of mice in groups B and C.The lung inflammation and mucus secretion in groups D and E were significantly alleviated than that of groups B and C.Number of total cells(63.50?5.12) andeosinophils(15.32?3.04) in BALF decreased in group B.Compared with group B,the number of total cells in groups D(55.3?5.20) ? 104 /ml and E(41.00?4.91) ?104 /ml greatly decreased(P