poly(D,L-lactic-co-glycolic) Acid Research Articles

Comparative Study of PLGA in-situ Implant and Nanoparticle Formulations of Entecavir; in-vitro and in-vivo evaluation

Entecavir (Baraclude®) is used daily as a long-term treatment for hepatitis-B virus infections. In this study a sustained injectable biodegradable in-situ implant (ISI) and polymeric nanoparticles (NPs) of Entecavir were prepared using Poly-d,l-lactic-co-glycolic acid (PLGA) polymer and evaluated for their shape, saturation solubility, in-vitro release and in-vivo efficacy. The pharmacokinetic parameters of Entecavir formulations were studied in rats following intramuscular injection, and the data was analyzed using one-way analysis of variance (ANOVA). TEM photographs showed that the ISI had a porous surface after exposure to Sörensen phosphate buffer pH 7.4 for 24 h, and Entecavir loaded NPs had a spherical structure with a smooth surface. The entrapment efficiency of Entecavir NPs was in the range of 47.03–77.84%. The pharmacokinetic studies showed a significant reduction (p < 0.05) in the Cmax from 353.75 for the pure Entecavir to 16.70 and 172.85 ng/ml for the NPs and ISI formulations, respectively. The AUC0-∞ also increased significantly from 211.32 ng/ml.h for pure Entecavir to 1520.64 and 2363.52 ng/ml.h for ISI and NP formulations, respectively. This study showed the feasibility of intramuscular ISI and NP formulations loaded with Entecavir which exhibit sustained release profiles and a promising strategy for the treatment of chronic hepatitis-B.

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.

Bioglass/PLGA associated to photobiomodulation: effects on the healing process in an experimental model of calvarial bone defect

Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.

Enhanced cancer therapy with pH-dependent and aptamer functionalized doxorubicin loaded polymeric (poly D, L-lactic-co-glycolic acid) nanoparticles

Aptamer based drug delivery systems are gaining the importance in anticancer therapy due to their targeted drug delivery efficiency without harming the normal cells. The present work formulated the pH-dependent aptamer functionalized polymer-based drug delivery system against human lung cancer. The prepared aptamer functionalized doxorubicin (DOX) loaded poly (D, L-lactic-co-glycolic acid) (PLGA), poly (N-vinylpyrrolidone) (PVP) nanoparticles (APT-DOX-PLGA-PVP NPs) were spherical in shape with an average size of 87.168 nm. The crystallography and presence of the PLGA (poly (D, L-lactic-co-glycolic acid)) and DOX (doxorubicin) in APT-DOX-PLGA-PVP NPs were indicated by the X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FTIR), and 1H and 13C nuclear magnetic resonance spectrometer (NMR). The pH-dependent aptamer AS1411 based drug release triggered the cancer cell death was evidenced by cytotoxicity assay, flow cytometry, and fluorescent microscopic imaging. In addition, the cellular uptake of the DOX was determined and the apoptosis-related signaling pathway in the A549 cells was studied by Western blot analysis. Further, the in vivo study revealed that mice treated with APT-DOX-PLGA-PVP NPs were significantly recovered from cancer as evident by mice weight and tumor size followed by the histopathological study. It was reported that the APT-DOX-PLGA-PVP NPs induced the apoptosis through the activation of the apoptosis-related proteins. Hence, the present study revealed that the APT-DOX-PLGA-PVP NPs improved the therapeutic efficiency through the nucleolin receptor endocytosis targeted drug release.

PLGA based particles as “drug reservoir” for antitumor drug delivery: characterization and cytotoxicity studies

Doxorubicin (DOX) is commonly used to treat several tumor types, but its severe side effects, primarily cardiotoxicity, represent a major limitation for its use in clinical settings.In this study we developed and characterized biodegradable and stable poly(D,L-lactic-co-glycolic) acid (PLGA) submicrocarriers employing an osmosis-based patented methodology, which allowed to optimize the drug loading efficiency up to 99%.Proceeding from this, we evaluated on MCF-7, a human breast cancer cell line, the ability of PLGA to promote the internalization of DOX and to improve its cytotoxicity in vitro. We found that the in vitro uptake efficiency is dramatically increased when DOX is loaded within PLGA colloidal carriers, which adhere to the cell membrane behaving as an efficient drug reservoir. In fact, the particles provide a diffusion-driven, sustained release of DOX across the cell membrane, resulting in high drug concentration. Accordingly, the cytotoxic analysis clearly showed that DOX-loaded PLGA exhibit a lower 50% inhibitory concentration than free DOX. The decay time of cell viability was successfully compared with DOX diffusion time constant from PLGA.The overall in vitro results highlight the potential of DOX-loaded PLGA particles to be employed as vectors with improved antitumor efficacy.

Green chemistry mediated synthesis of PLGA-Silver nanocomposites for antibacterial synergy: Introspection of formulation parameters on structural and bactericidal aspects

A facile synthesis of silver nanoparticles (Ag-NPs) was carried out by employing a biomimetic approach. Herein, the extract of Eugenia jambolana was used as the precursor excipients, which played a synergistic role in the reduction and capping (stabilization) of Ag+ into zero valent (viz. Ag 0) Ag-NPs. In addition to this, the study was further directed towards the encapsulation of Ag-NPs within the matrix of the biodegradable polymer viz. poly-D, L-lactic-co-glycolic acid (PLGA).The current enthusiasm of polymer-silver nanocomposites (PLGA-Ag NCs) in biomedical applications is because a versatile framework must have antimicrobial action devoid of the release of any toxic product. Modified emulsion method was utilized for the fabrication of PLGA-Ag NCs (viz. PLGA-Ag NC (PEG) and PLGA-Ag NC (P80)). The physicochemical properties of the developed nanostructured systems were thoroughly probed using varied state of microscopic and spectroscopic techniques.Disc diffusion and time-kill assay were performed on bacterial strains viz. Escherichia coli (E.coli, MTCC 40), and Pseudomonas aeruginosa (P.aeruginosa MTCC 4673) for evaluating the antibacterial activity of Ag-NPs and PLGA-Ag NCs. Both the antibacterial assays highlighted the superiority of PLGA-Ag NCs in inciting an escalated bactericidal effect in comparison to Ag-NPs and standard antibiotic (viz. norfloxacin (NFC)), respectively. Hence, the present research article thus reports a novel biocompatible approach to tackle the overgrowing problem of antibiotic resistance.

Prolonging food shelf-life by dual actives release from multi-layered polymer particles.

Biodegradable polymer based 'controlled release packaging' technology has ability to release packaging actives in controlled manner to prolong the food shelf-life. Currently available systems are not sufficiently capable of releasing multiple actives in sustainable fashion. Hence, the purpose of this study was to develop dual actives (antioxidant and antibacterial) loaded multilayered microparticles in one step and to release them at rates suitable for long-term inhibition of bacterial growth as well as lipid oxidation in food. In order to achieve this goal, 2 kinds of multilayered polymer particles made up of PLLA (Poly(l-lactic acid)) and PLGA (Poly(dl-lactic-co-glycolic acid) with varying viscosity were developed using emulsion solvent evaporation method. Surprisingly, low viscous PLGA resulted tri-layered particles (PLGA/PLLA/PLGA: shell/middle/core) instead of bi-layered (PLGA/PLLA: shell/core) particles as observed for high viscous PLGA. The mechanism of formation of tri-layered particles was investigated in detail. The outermost layer consisted of relatively more hydrophilic polymer PLGA along with benzoic acid (antibacterial) and the inner core comprised of hydrophobic polymer PLLA and tocopherol (antioxidant). Release study demonstrated that release rate of dual actives were significantly accelerated from tri-layered particles in comparison to bi-layered one and their release profiles can be well explained with the help of Ridger-Peppas model. Both sets of particles exhibited long-term antibacterial (against both Escherichia coli and Staphylococcus aureus) as well as antioxidant effect over a period of 60 days. The results show for the first time the feasibility of using multilayered microparticles to prolong the food shelf-life by simultaneous release of multiple actives.

Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand-Dextran Nanogels.

Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of transporting TSPO ligands inside cancer cells, inducing survival inhibition in cancer cells and producing mitochondrial morphology modification. The aim of this work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO-Dex) that are useful as potential delivery systems of two TSPO ligands as apoptotic agents. Synthesis and complete characterization of TSPO–dextran conjugates, an average molecular weights analysis, TSPO ligand release profiles, thermal behaviour and swelling studies were achieved. NG preparation, characterization and in vitro biological studies were also performed. The release of TSPO ligands released from dextran conjugates at 37 °C occurred in human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity studies demonstrated that NGs produced from TSPO ligand–dextran conjugates induce survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven by fluorescence microscopy.

Injectable PLGA Adefovir microspheres; the way for long term therapy of chronic hepatitis-B

For patient convenience, sustained release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres were formulated to relieve the daily use of the drug which is a problem for patients treated from chronic hepatitis-B. PLGA microspheres were prepared and characterized by entrapment efficiency, particle size distribution and scanning electron microscopy (SEM). In-vitro release and in-vivo studies were carried out. Factors such as drug: polymer ratio, polymer viscosity and polymer lactide content were found to be important variables for the preparation of PLGA Adefovir microspheres. Fourier transform infrared (FTIR) analysis and differential scanning calorimetry (DSC) were performed to determine any drug-polymer interactions. One way analysis of variance (ANOVA) was employed to analyze the pharmacokinetic parameters after intramuscular injection of the pure drug and the selected PLGA microspheres into rats. FTIR and DSC revealed a significant interaction between the drug and the polymer. Reports of SEM before and after 1 and 24 h release showed that the microspheres had nonporous smooth surface even after 24 h release. The entrapment efficiency ranged between 55.83 and 86.95% and in-vitro release studies were continued for 16, 31 and 90 days. The pharmacokinetic parameters and statistical analysis showed a significant increase in the Tmax, AUC0–t and MRT, and a significant decrease in the Cmax of the tested formulation (p < 0.05). Results demonstrated that PLGA Adefovir microspheres could be used for long-term treatment of chronic hepatitis-B instead of the daily dose used by the patient.

PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure

Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA gyrase enzyme activity. However, photodegradation in the presence of UVA limits its antibacterial activity and induces phototoxicity. Thus, to encounter this problem, we have developed poly d,l-lactic-co-glycolic acid (PLGA) loaded SPFX nanoparticles. Here, we have performed a comparative antibacterial activity of SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity assay. Under environmental UVA exposure, photoexcited SPFX significantly generates ROS, DNA damage and mitochondrial mediated cell death in comparison to PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA, bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via alteration in membrane integrity of mitochondria and lysosome in comparison to PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of pro-apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis. Our finding suggests that controlled release of SPFX from PLGA-SPFX-NPs can reduce its side effects and enhance its antibacterial activity. Thus, nanotization of fluoroquinolones will be a significant step to reduce the problem of resistance and phototoxicity of this group.

Gene expression profiling of chicken cecal tonsils and ileum following oral exposure to soluble and PLGA-encapsulated CpG ODN, and lysate of Campylobacter jejuni

Campylobacter jejuni (C. jejuni) is a leading bacterial cause of food-borne illness in humans. Contaminated chicken meat is an important source of infection for humans. Chickens are not clinically affected by colonization, and immune responses following natural infection have limited effects on bacterial load in the gut. Induction of intestinal immune responses may possibly lead to a breakdown of the commensal relationship of chickens with Campylobacter. We have recently shown that soluble and poly D, L-lactic-co-glycolic acid (PLGA)-encapsulated CpG oligodeoxynucleotide (ODN) as well as C. jejuni lysate, are effective in reducing the intestinal burden of C. jejuni in chickens; however, the mechanisms behind this protection have yet to be determined. The present study was undertaken to investigate the mechanisms of host responses conferred by these treatments. Chickens were treated orally with soluble CpG ODN, or PLGA-encapsulated CpG ODN, or C. jejuni lysate, and expression of cytokines and antimicrobial peptides was evaluated in cecal tonsils and ileum using quantitative RT-PCR. Oral administration of soluble CpG ODN upregulated the expression of interferon (IFN)-γ, interleukin (IL)-1β, CXCLi2, transforming growth factor (TGF)-β4/1, IL-10 and IL-13, while treatment with PLGA-encapsulated CpG ODN upregulated the expression of IL-1β, CXCLi2, TGF-β4/1, IL-13, avian β-defensin (AvBD) 1, AvBD2 and cathelicidin 3 (CATHL-3). C. jejuni lysate upregulated the expression of IFN-γ, IL-1β, TGF-β4/1, IL-13, AvBD1, and CATHL-3. In conclusion, induction of cytokine and antimicrobial peptides expression in intestinal microenvironments may provide a means of reducing C. jejuni colonization in broiler chickens, a key step in reducing the incidence of campylobacteriosis in humans.

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response

Objectives: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer.Methods: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study.Results: The final NP had a small size (around 120 nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8 ± 1.1% and 99.5 ± 0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs.Conclusions: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.

Effect of nanoencapsulation using PLGA on antioxidant and antimicrobial activities of guabiroba fruit phenolic extract

Guabiroba fruit has been highlighted for its high phytochemical content, particularly of phenolic compounds. The stability, bioavailability, and bioactivity of these compounds can be enhanced by nanoencapsulation, to improve functionality. Poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles containing phenolic extract of guabiroba (GPE) were synthesized by an adapted emulsion-evaporation method and their physico-chemical and functional properties were studied at two lactic to glycolic acid ratios (50:50 and 65:35). Higher (P<0.05) or equivalent antioxidant capacity compared to free GPE were observed for GPE-loaded nanoparticles. Free extract and PLGA nanoparticles were effective inhibitors of Listeria innocua, with lower (P<0.05) GPE concentrations required for inhibition when nanoencapsulated. Also, reduction of ROS generation in non-cancer cells was achieved with lower GPE concentrations (P<0.05) after encapsulation. These results suggest that PLGA nanoparticles can be used as a delivery system for phenolic compounds at lower levels than originally required for enhanced functional properties.

Drug-Loaded PLGA Electrospraying Porous Microspheres for the Local Therapy of Primary Lung Cancer via Pulmonary Delivery.

Nonsmall-cell lung cancer is a severe disease with high morbidity and mortality. However, the systemic administration of anticancer drugs generally leads to serious toxicity and low anti-lung cancer efficiency because of very limited drug distribution in the lung. In our previous research, we have confirmed the high anti-lung cancer effect of inhalable oridonin microparticles in spite of their long and complicated preparation process. Here, we develop a novel, simple, and quick method for preparing inhalable oridonin-loaded poly(d,l-lactic-co-glycolic)acid (PLGA) porous microspheres using the electrospraying technique. The formulation and preparation processes were screened. The electrospraying porous microspheres (EPMs) were rough, porous, and suitable for pulmonary delivery. Most of the oridonin was released from the EPMs within 20 h based on drug diffusion and via PLGA erosion. The EPMs exhibited efficient lung deposition in vitro and in vivo because of their ideal aerodynamic diameters. Chemical carcinogens were used to prepare primary lung cancer rat models by direct pulmonary delivery. The EPMs showed high anti-lung cancer effect after pulmonary delivery according to CT images and pathology. Inhibition of angiogenesis and enhancement of lung cancer cell apoptosis could be the major anticancer mechanism. Electrospraying is an efficient method for the preparation of inhalable drug-loaded porous microspheres. The oridonin-loaded EPMs are promising dry powder inhalers for the local therapy of primary lung cancer.

Microfluidic-assisted nanoprecipitation of antiviral-loaded polymeric nanoparticles

The chemical treatment called “chemotherapy of plants” consists in the in vivo administration of substances able to interfere with viral replication. The current availability of synthetic molecules with a high chemotherapeutic index, i.e. with a high ratio between the maximum concentration tolerated and the minimum effective, together with the possibility to further widen the therapeutic window by the use of appropriate nanocarriers, seems to open on the application level of a novel chemical approach to treat plant viral infections. Ribavirin, for example, is a synthetic water-soluble nucleoside that possesses broad spectrum activity against a variety of DNA and RNA plant viruses. As well known, water-soluble drugs are generally difficult to encapsulate in solid particles. Chemical modification of these drugs, such as esterification, may increase their encapsulation efficiency, but may also decrease bioactivity. In this work we have synthesized stable solid monodispersed PLGA (poly-d,l-lactic-co-glycolic acid) NPs with diameters ranging from 50 to 200nm containing ribavirin by using a microfluidic reactor with a flow-focusing geometry. Previous work carried out in our lab showed an improvement of drug loading efficiency when using a microfluidic approach in comparison with traditional nanoprecipitation methods for nanoencapsulation. On this basis we optimized Ribavirin loading within PLGA NPs by investigating the influence of different operating conditions, such as polymer concentration, flow rate ratio, τmix, microreactor-focusing channel diameter and length, on nanoparticle size and morphology. NPs characterization was performed by Dynamic light scattering (DLS) measurements and by scanning electron microscopy (SEM). The synthesized NPs showed a significant drug loading efficiency.

The application of novel nano-thermal and imaging techniques for monitoring drug microstructure and distribution within PLGA microspheres

Poly (d,l-lactic-co-glycolic) acid (PLGA) based microspheres have been extensively used as controlled drug release systems. However, the burst effect has been a persistent issue associated with such systems, especially for those prepared by the double emulsion technique. An effective approach to preventing the burst effect and achieving a more ideal drug release profile is to improve the drug distribution within the polymeric matrix. Therefore, it is of great importance to establish a rapid and robust tool for screening and optimizing the drug distribution during pre-formulation. Transition Temperature Microscopy (TTM), a novel nano-thermal and imaging technique, is an extension of nano-thermal analysis (nano-TA) whereby a transition temperature is detected at a localized region of a sample and then designated a color based on a particular temperature/color palette, finally resulting in a coded map based on transition temperatures detected by carrying out a series of nanoTA measurements across the surface of the sample. In this study, we investigate the feasibility of applying the aforementioned technique combined with other thermal, imaging and structural techniques for monitoring the drug microstructure and spatial distribution within bovine serum albumin (BSA) loaded and nimodipine loaded PLGA microspheres, with a view to better predicting the in vitro drug release performance.

Nanotechnology-Based Cancer Vaccine.

Nanotechnology offers invaluable tools to tailor cancer vaccines in order to generate robust antitumor immune response. Among the types of vehicles for cancer vaccines, nanoparticles (NPs) are easier to produce with better scalability. Several nanostructures have been discussed in literature as potential delivery systems for cancer antigens. Here, we focus on polymeric NPs fabricated from poly(D,L-lactic-co-glycolic) acid (PLGA). We describe how to prepare and characterize such NPs loaded with ovalbumin (OVA) antigen and immune adjuvant monophosphoryl lipid A (MPLA). We further describe methods to test the immune efficacy of such NPs in vitro and in vivo.

Coencapsulation of trans-Dehydrocrotonin and trans-Dehydrocrotonin:hydroxypropyl-β-cyclodextrin into Microparticles

The aim of this study was to develop and characterize poly-e-caprolactone (PCL) and poly(D,L-lactic-co-glycolic)-acid (PLGA) microparticles containing coencapsulated trans-dehydrocrotonin (t-DCTN) and t-DCTN:hydroxypropyl-β-cyclodextrin inclusion complex (t-DCTN:HP-β-CD), with t-DCTN loaded at concentrations ranging from 11.25 to 45.00 mg. A preformulation study was carried out using a 24-1 fractional factorial design. Microparticles were prepared using the double w/o/w emulsion-solvent evaporation method. The coencapsulated t-DCTN:HP-β-CD-loaded PLGA microparticles (t-DCTN/t-DCTN:HP-β-CD/PLGA-MPs) presented a smaller particle size (9.6 ± 0.1 µm) and higher drug loading (13.93 ± 0.05%, corresponding to 90.1 ± 0.3% of encapsulation efficiency, EE) and t-DCTN-loaded PLGA microparticles (t-DCTN/PLGA-MPs) presented particle size of 37.0 ± 0.2 µm and drug loading of 10.12 ± 0.01% (EE of 71.2 ± 0.1%). The coencapsulation of t-DCTN and t-DCTN:HP-β-CD into PLGA microparticles increased drug loading (50%) and improved the drug controlled release (k2 = 0.0475 and De = 0.0475 × 10-11 cm2 s-1). Taking into account these findings, new oral formulation of PLGA microparticles containing coencapsulated t-DCTN and t-DCTN:HP-β-CD are available as biocompatible drug delivery systems for further pharmacological purposes.

Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles

To improve the solubility and anticancer activity of albendazole (ABZ), chitosan (CS)-coated poly-dl-lactic-co-glycolic acid (PLGA) nanoparticles were developed. CS was used to coat ABZ-loaded PLGA nanoparticles to enhance both mucoadhesiveness and colloidal stability. CS-coated PLGA nanoparticles were prepared by suspending the nanoparticles in CS solution after solvent diffusion. The CS-coated PLGA nanoparticles were characterized, and ABZ release was studied in vitro from various formulations. The mucoadhesive properties and in vitro anticancer activities of CS-coated PLGA nanoparticles were investigated by measurement of zeta potentials and the MTT assay, respectively. Spherical nanoparticles below 500nm in diameter were successfully prepared; the particle size distribution was narrow. Complete encapsulation of ABZ in CS-coated PLGA nanoparticles was confirmed by SEM, FTIR, DSC, and XRD. The particle sizes of CS-coated PLGA nanoparticles were in the range of 260–480nm; the encapsulation efficiency was 43.4–54.6%; and the yield 58.5–67.8%. The zeta potential of CS-coated nanoparticles was above +27mV and stability was maintained for 4 weeks. At pH 7.4, the in vitro release of ABZ from nanoparticles (P188-5) was 200-fold higher than that from untreated ABZ; this persisted for 12h. Moreover, ABZ release from CS-coated PLGA nanoparticles (P188-CS0.5) was 1.5-fold higher than that from untreated ABZ at pH 1.2. Additionally, the ABZ-loaded CS-coated nanoparticles exhibited superior mucoadhesion and improved cytotoxicity. The results show that CS coating of PLGA nanoparticles may improve the anticancer effect and the mucoadhesive properties of ABZ-loaded nanoparticles.