PLGA

Objective(s): The current study reports investigation of codelivery by PLGA nanoparticles (NPs) loaded with crocetin
(Cro), a natural carotenoid dicarboxylicHYPERLINK “http://en.wikipedia.org/wiki/Carboxylic_acid” acid that is found
in the crocus flower, and Doxorubicin (DOX).
Materials and Methods: Double emulsion/solvent evaporation method was used for preparation of PLGA nanoparticles
containing Dox and Cro. Characterizations of prepared NPs were investigated by atomic force microscopy (AFM) and
dynamic light scattering analysis. In vitro Cytotoxicity of DOX and Cro loaded PLGA NPs (PLGA-DOX-Cro) on
MCF-7 cell line was evaluated using MTT test. Flow cytometry experiments were implemented to distinguish cells
undergoing apoptosis from those undergoing necrosis. Furthermore the expression of caspase 3 was examined by
western blot analysis.
Results: The prepared formulations had size of 150- 300 nm. Furthermore, PLGA-DOX-Cro nanoparticles inhibited
MCF-7 tumor cells growth more efficiently than either DOX or Cro alone at the same concentrations, as quantified by
MTT assay and flow cytometry. Studies on cellular uptake of DOX-Cro-NPs demonstrated that NPs were effectively
taken up by MCF-7 tumor cells.
Conclusion: This study suggested that DOX-Cro-NPs may have promising applications in breast cancer therapy.

This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.

Lung cancer is the leading cause of death (male and female) globally, responsible for over 1.8 million deaths. Although there have been some advances in the treatment of lung cancer, the early detection remains an issue globally. The necessity of new drugs able to efficiently accumulate and image lung cancer is quite required. In this study was developed PLGA nanoparticles loaded with Lamivudine (PLGA-NPs-LAM). The PLGA-NPs-LAM was characterized, radiolabeled with radioactive technetium (99m Tc), and in vitro evaluated. The results showed a medium size of 203.667 ± 1.436 nm, with a PDI value of 0.063 ± 0.052, and a superficial charge of − 4.597 ± 0.368 mV. The entrapment efficacy demonstrated was 48.346 ± 1.742% of LAM. Radiolabeling of PLGA-NPs-LAM with Technetium-99 m (99m Tc) showed high efficiency (>93%). The in vitro assay human lung cancer (A-549) and human fibroblast (L-929) cell lines showed that the NPs were higher uptake in A-549 line than L-929. The data demonstrated that [ 99m Tc]Tc-PLGA-NPs-LAM may be a promising agent for lung cancer diagnosis.

Microsphere-based controlled release technologies have been utilized for the long-term delivery of proteins , peptides and antibiotics, although their synthesis poses substantial challenges owing to formulation complexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process as a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining control over particle structure and size. Here we report a successful formulation recipe used to generate spherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel thermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN 2) collection scheme. We show how size, shape and porosity of resulting microspheres can be controlled by judiciously varying electrospray processing parameters and we demonstrate examples in which the particle size (and porosity) affect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties are characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric analysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1 week) of an active agent, enabling sustained release of a dye with minimal physical degradation and have verified the potential of scalable electrospray technologies for an innovative TIPS-based microsphere production protocol.

The calorimetric investigation of non-coated and chitosan-coated PLGA nanoparticles (NP) shows that at initial temperatures of heating particle swelling takes place what results in an internal architectural change at lower than physiological temperature. It has shown that the temperature of NP tightness perturbing depends on solvent polarity: as more polar is the solvent more stable are particles. The break of existing bonds in NP shell is accompanied with heat absorption peak which undergoes significant changes depending on heating rate. In the wide pH 2–8 interval in transition temperature no changes occurred. The obtained results show that such NP could be used in acidic area for drug transfer, which gives possibility to take medicine orally. It was shown that DNA attaches only to chitosan-coated NP. The optimal ratio for DNA loading onto the NP was found to be 7:1 (WNP/WDNA).

The development of new gene-editing technologies has fostered the need for efficient and safe vectors capable of encapsulating large nucleic acids. In this work we evaluate the synthesis of large-size plasmid-loaded PLGA nanoparticles by double emulsion (considering batch ultrasound and microfluidics-assisted methodologies) and magnetic stirring-based nanoprecipitation synthesis methods. For this purpose, we characterized the nanoparticles and compared the results between the different synthesis processes in terms of encapsulation efficiency, morphology, particle size, polydispersity, zeta potential and structural integrity of loaded pDNA. Our results demonstrate particular sensibility of large pDNA for shear and mechanical stress degradation during double emulsion, the nanoprecipitation method being the only one that preserved plasmid integrity. However, plasmid-loaded PLGA nanoparticles synthesized by nanoprecipitation did not show cell expression in vitro, possibly due to the slo...

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29...

The purpose of this study was to prepare poly (D-L) lactide-co-glycolide (PLGA) and poly ε-caprolactone (PCL) nanofibers containing metronidazole and amoxicillin using an electrospinning process as intrapocket sustained-release drug delivery systems for the treatment of periodontal diseases. Scanning electron microscopy showed that the drug containing PLGA and PCL nanofibers produced from the electrospinning process was uniform and bead-free in morphology. The obtained nanofibers had a strong structure and resisted external tension according to the tensiometry results. The cytotoxicity results indicated acceptable cell viability (>80%). Quantification by high-performance liquid chromatography showed almost complete in vitro drug release between 7 and 9 days, whereas 14 days were required for complete drug release in vivo. No significant signs of irritation or inflammatory reaction were detected after three weeks of subcutaneous implantation of nanofibers in the animal models, thu...

It has been demonstrated the feasibly of using PLGA nanoparticles to promote the encapsulation of novel anti-diabetic sulphonylhydrazone and antitumor N-acylhydrazone derivatives. The motivation is to further demonstrate the possibility of long-term release of anti-diabetic as well as higher accumulation of the antitumor derivative by using the nanotechnology-based production. The produced nanoparticles were obtained by the nanoprecipitation method, which revealed to be effective in the encapsulation of the bioactive compounds. The determined sizes were in the range of ~100 nm, which are supposed to be suitable for both potential applications. The preliminary experimental data demonstrated the formation of stable nanosystems and further experiments are underway in order to determine the loading content, encapsulation efficiency and release profile of the hydrophobic bioactive compounds.

Growth factors (GFs) are very critical in stem cell differentiation and tissue regeneration. Therefore GF delivery carriers have been a major subject in tissue engineering research. In this study, we prepare and optimize core-shell microcapsules (C-S MCs) for dual GF delivery. The C-S MCs, composed of an alginate shell and poly(lactic-co-glycolic) acid (PLGA) core, are fabricated using an electrodropping method via custom-made coaxial needles. They are 198±38 µm in diameter with an average core size of 90±13 µm, and they are fabricated using an alginate concentration of 1% (w/v), an electrical voltage of 11 kV, and an inner syringe flow rate of 50 µL/min. Using this platform, dual GFs, bone morphogenetic protein (BMP-2) and vascular endothelial growth factor (VEGF) are encapsulated in the alginate shell and PLGA core, respectively. In vitro release tests of dual GF-loaded C-S MCs reveal early release of BMP-2, followed by VEGF on a temporal release profile of 28 days. In vitro study of the dual GF-loaded MCs demonstrates their osteogenic activity with preosteoblasts; osteogenic markers (osteocalcin and type I collagen) are upregulated and both calcium content and alkaline phosphatase (ALP) activity also increased. In addition, C-S MCs combined with collagen and preosteoblasts were subcutaneously transplanted to the dorsal region of nude mice for 3 weeks. Analysis of the retrieved constructs exhibits that both osteogenesis and angiogenesis were more active in the group containing dual GF-loaded MCs, along with deep penetration of blood vessels inside the construct, compared to blank MCs or single GF (BMP-2)-loaded MCs. This study proposes a dual GF delivery carrier using C-S MCs and demonstrates the feasibility of C-S MCs in the induction of osteogenesis and angiogenesis.

Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic- co-glycolic acid) (PLGA) nanoparticles (NPs). The majority of VEGF was released gradually over 2–4 days from the NPs as determined by an ELISA release kinetics experiment. An in vitro aortic ring bioassay was used to verify the bioactivity of VEGF-NPs compared with empty NPs and no treatment. A mouse femoral artery ischemia model was then used to measure revascularization in VEGF-NP-treated limbs compared with limbs treated with naked VEGF and saline. 129/Sv mice were anesthetized with isoflurane, and a region of the common femoral artery and vein was ligated and excised. Mice were then injected with VEGF-NPs, naked VEGF, or s...

Biodegradable thermosensitive triblock copolymers based on poly (ethylene glycol) and poly [(lactic acid)-co-(glycolic acid)](PLGA-PEG-PLGA) with PLGA/PEG weight ratio in the range of 1.5–3.0 and LA/GA molar ratio equal to 2.4 or 3.0 were prepared via ring opening ...

The development of a new drug active substance is not only time-consuming and expensive, but also a chain of operations that often fails. However, increasing the bioavailability, effectiveness, safety, or targeting the drugs used in clinic by various methods, such as nanoparticles (NPs), may be a more effective way of using them in clinic. In addition, NP formulations are becoming increasingly popular in modern medical treatments. Angiogenesis, formation of new capillaries from a pre-existing one, fundamentally occurs in physiological processes such as wound healing, embryogenesis and menstrual cycle, also has a vital role in pathology of cancer, psoriasis, diabetic retinopathy and chronic inflammation. The Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM) assay is a useful, well established and animal alternative in vivo procedure for evaluation of anti-inflammatory potentials and anti-irritant properties of nano drug delivery systems. In this study, diclofenac sodium (D...

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and
osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type
and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In
the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calciummineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highlywarranted for
the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics.
The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.