Special Issue "PLGA Based Drug Carrier and Pharmaceutical Applications"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 October 2019).

Special Issue Editors

Prof. Dr. Maria Carmo Pereira
Website
Guest Editor
LEPABE–Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: novel nano-engineered biomaterials for therapeutic applications; fluorinated peptides and active molecules interactions with surfaces and lipid model membranes; design of inhibitors of Alzheimer fibrillogenesis; antibody-directed nanocarriers for Alzheimer’s disease; electrochemical immunosensors for detection of degenerative disease biomarkers; air pollutants/exposure risk assessment
Special Issues and Collections in MDPI journals
Dr. Joana A. Loureiro
Website
Guest Editor
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: nanotechnology and interfacial phenomena; effects of fluorinated systems and peptides on the aggregation of amyloid beta peptide; conformational studies of proteins and peptides self-organized systems and polymer surfaces; design and production of inorganic and polymeric nano-systems for pharmaceutical and food applications
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful polymer used to produce therapeutic devices, such as drug carriers (DC). This is one of the few polymers Food and Drug Administration (FDA) approved for human administration due to its biocompatibility and biodegradability.

DC produced with PLGA has gained enormous attention over recent years for their ability to be versatile vehicles to transport different type of drugs e.g. hydrophilic or hydrophobic small molecules or macromolecules and protect them from degradation and uncontrolled release. These drug delivery systems (DDS) have the possibility to modify their surface properties, to improve their interactions with biological materials. Furthermore, they present the possibility to be conjugated with specific target molecules to reach specific tissues or cells. This special issue

They are being used for different therapeutic applications, such as vaccination, cancer, neurological disorders, inflammation and other diseases.

This special issue aims to focus the recent progress of PLGA as drug carriers for new pharmaceutical applications

Prof. Dr. Maria Carmo Pereira
Dr. Joana Loureiro
Guest Editors

Manuscript Submission Information

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Keywords

  • PLGA
  • Drug delivery systems
  • Drug carrier
  • Nanoparticles
  • Polymeric materials

Published Papers (20 papers)

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Editorial

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Open AccessEditorial
PLGA Based Drug Carrier and Pharmaceutical Applications: The Most Recent Advances
Pharmaceutics 2020, 12(9), 903; https://doi.org/10.3390/pharmaceutics12090903 - 22 Sep 2020
Abstract
Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful polymers that has been used to produce medicines, such as drug carriers (DC) [...] Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)

Research

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Open AccessArticle
Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation
Pharmaceutics 2020, 12(2), 118; https://doi.org/10.3390/pharmaceutics12020118 - 01 Feb 2020
Cited by 4
Abstract
Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing [...] Read more.
Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
MRI/Photoluminescence Dual-Modal Imaging Magnetic PLGA Nanocapsules for Theranostics
Pharmaceutics 2020, 12(1), 16; https://doi.org/10.3390/pharmaceutics12010016 - 21 Dec 2019
Cited by 2
Abstract
Developing multifunctional and biocompatible drug delivery nanoplatforms that integrate high drug loads and multiple imaging modalities avoiding cross-interferences is extremely challenging. Here we report on the successful chemical reaction of the high quantum yield biodegradable and photoluminescent polyester (BPLP) with the poly(lactic-co-glycolic acid) [...] Read more.
Developing multifunctional and biocompatible drug delivery nanoplatforms that integrate high drug loads and multiple imaging modalities avoiding cross-interferences is extremely challenging. Here we report on the successful chemical reaction of the high quantum yield biodegradable and photoluminescent polyester (BPLP) with the poly(lactic-co-glycolic acid) (PLGA) polymer to fabricate biocompatible photoluminescent nanocapsules (NCs). Furthermore, we transform the PLGA-BPLP NCs into a magnetic resonance (MR)/photoluminescence dual-modal imaging theranostic platform by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the polymeric shell. In vitro phantoms confirmed the excellent MRI-r2 relaxivity values of the NCs whilst the cellular uptake of these NCs was clearly observed by fluorescence optical imaging. Besides, the NCs (mean size ~270 nm) were loaded with ~1 wt% of a model protein (BSA) and their PEGylation provided a more hydrophilic surface. The NCs show biocompatibility in vitro, as hCMEC/D3 endothelial cells viability was not affected for particle concentration up to 500 μg/mL. Interestingly, NCs decorated with SPIONs can be exploited for magnetic guiding and retention. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
Pharmaceutics 2019, 11(12), 665; https://doi.org/10.3390/pharmaceutics11120665 - 09 Dec 2019
Cited by 3
Abstract
For parenteral controlled drug release, the desired zero order release profile with no lag time is often difficult to achieve. To overcome the undesired lag time of the current commercial risperidone controlled release formulation, we developed PLGA–lipid microcapsules (MCs) and PLGA–lipid microgels (MGs). [...] Read more.
For parenteral controlled drug release, the desired zero order release profile with no lag time is often difficult to achieve. To overcome the undesired lag time of the current commercial risperidone controlled release formulation, we developed PLGA–lipid microcapsules (MCs) and PLGA–lipid microgels (MGs). The lipid phase was composed of middle chain triglycerides (MCT) or isopropylmyristate (IPM). Hydroxystearic acid was used as an oleogelator. The three-dimensional inner structure of Risperidone-loaded MCs and MGs was assessed by using the invasive method of electron microscopy with focused ion beam cutting (FIB-SEM) and the noninvasive method of high-resolution nanoscale X-ray computed tomography (nano-CT). FIB-SEM and nano-CT measurements revealed the presence of highly dispersed spherical structures around two micrometres in size. Drug release kinetics did strongly depend on the used lipid phase and the presence or absence of hydroxystearic acid. We achieved a nearly zero order release without a lag time over 60 days with the MC-MCT formulation. In conclusion, the developed lipid-PLGA microparticles are attractive alternatives to pure PLGA-based particles. The advantages include improved release profiles, which can be easily tuned by the lipid composition. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Monitoring the Fate of Orally Administered PLGA Nanoformulation for Local Delivery of Therapeutic Drugs
Pharmaceutics 2019, 11(12), 658; https://doi.org/10.3390/pharmaceutics11120658 - 06 Dec 2019
Cited by 1
Abstract
One of the goals of the pharmaceutical sciences is the amelioration of targeted drug delivery. In this context, nanocarrier-dependent transportation represents an ideal method for confronting a broad range of human disorders. In this study, we investigated the possibility of improving the selective [...] Read more.
One of the goals of the pharmaceutical sciences is the amelioration of targeted drug delivery. In this context, nanocarrier-dependent transportation represents an ideal method for confronting a broad range of human disorders. In this study, we investigated the possibility of improving the selective release of the anti-cancer drug paclitaxel (PTX) in the gastro-intestinal tract by encapsulating it into the biodegradable nanoparticles made by FDA-approved poly(lactic-co-glycolic acid) (PLGA) and coated with polyethylene glycol to improve their stability (PLGA-PEG-NPs). Our study was performed by combining the synthesis and characterization of the nanodrug with in vivo studies of pharmacokinetics after oral administration in mice. Moreover, fluorescent PLGA-nanoparticles (NPs), were tested both in vitro and in vivo to observe their fate and biodistribution. Our study demonstrated that PLGA-NPs: (1) are stable in the gastric tract; (2) can easily penetrate inside carcinoma colon 2 (CaCo2) cells; (3) reduce the PTX absorption from the gastrointestinal tract, further limiting systemic exposure; (4) enable PTX local targeting. At present, the oral administration of biodegradable nanocarriers is limited because of stomach degradation and the sink effect played by the duodenum. Our findings, however, exhibit promising evidence towards our overcoming these limitations for a more specific and safer strategy against gastrointestinal disorders. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Dry Tablet Formulation of PLGA Nanoparticles with a Preocular Applicator for Topical Drug Delivery to the Eye
Pharmaceutics 2019, 11(12), 651; https://doi.org/10.3390/pharmaceutics11120651 - 04 Dec 2019
Cited by 3
Abstract
To enhance ocular drug bioavailability, a rapidly dissolving dry tablet containing alginate and drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles was proposed. For hygienic and easy administration of an accurate drug-dose with this tablet, the use of a preocular applicator was suggested. Herein, [...] Read more.
To enhance ocular drug bioavailability, a rapidly dissolving dry tablet containing alginate and drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles was proposed. For hygienic and easy administration of an accurate drug-dose with this tablet, the use of a preocular applicator was suggested. Herein, a dry tablet was prepared by embedding dexamethasone-loaded PLGA nanoparticles in alginate, which was deposited on the tip of the applicator. The nanoparticles were loaded with 85.45 μg/mg drug and exhibited sustained drug release for 10 h. To evaluate in vivo efficacy, dexamethasone concentration in the aqueous humor was measured after topical administration of the dry tablet, with the applicator, to rabbit eyes and was compared to that achieved with Maxidex®, a commercially-available dexamethasone eye drops. When applied with the preocular applicator, the dry tablet containing alginate could be fully detached and delivered to the eye surface. In fact, it showed up to 2 h of nanoparticle retention on the preocular surface due to tear viscosity enhancement, causing an estimated 2.6-fold increase in ocular drug bioavailability compared to Maxidex®. Therefore, the preocular applicator combined with a dry alginate tablet containing PLGA nanoparticles can be a promising system for aseptically delivering an accurate dose of ophthalmic drug with enhanced bioavailability. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
PLGA-BMP-2 and PLA-17β-Estradiol Microspheres Reinforcing a Composite Hydrogel for Bone Regeneration in Osteoporosis
Pharmaceutics 2019, 11(12), 648; https://doi.org/10.3390/pharmaceutics11120648 - 03 Dec 2019
Cited by 3
Abstract
The controlled release of active substances—bone morphogenetic protein 2 (BMP-2) and 17β-estradiol—is one of the main aspects to be taken into account to successfully regenerate a tissue defect. In this study, BMP-2- and 17β-estradiol-loaded microspheres were combined in a sandwich-like system formed by [...] Read more.
The controlled release of active substances—bone morphogenetic protein 2 (BMP-2) and 17β-estradiol—is one of the main aspects to be taken into account to successfully regenerate a tissue defect. In this study, BMP-2- and 17β-estradiol-loaded microspheres were combined in a sandwich-like system formed by a hydrogel core composed of chitosan (CHT) collagen, 2-hidroxipropil γ-ciclodextrin (HP-γ-CD), nanoparticles of hydroxyapatite (nano-HAP), and an electrospun mesh shell prepared with two external electrospinning films for the regeneration of a critical bone defect in osteoporotic rats. Microspheres were made with poly-lactide-co-glycolide (PLGA) to encapsulate BMP-2, whereas the different formulations of 17β-estradiol were prepared with poly-lactic acid (PLA) and PLGA. The in vitro and in vivo BMP-2 delivered from the system fitted a biphasic profile. Although the in vivo burst effect was higher than in vitro the second phases (lasted up to 6 weeks) were parallel, the release rate ranged between 55 and 70 ng/day. The in vitro release kinetics of the 17β-estradiol dissolved in the polymeric matrix of the microspheres depended on the partition coefficient. The 17β-estradiol was slowly released from the core system using an aqueous release medium (Deff = 5.58·10−16 ± 9.81·10−17m2s−1) and very fast in MeOH-water (50:50). The hydrogel core system was injectable, and approximately 83% of the loaded dose is uniformly discharged through a 20G needle. The system placed in the defect was easily adapted to the defect shape and after 12 weeks approximately 50% of the defect was refilled by new tissue. None differences were observed between the osteoporotic and non-osteoporotic groups. Despite the role of 17β-estradiol on the bone remodeling process, the obtained results in this study suggest that the observed regeneration was only due to the controlled rate released of BMP-2 from the PLGA microspheres. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles
Pharmaceutics 2019, 11(11), 590; https://doi.org/10.3390/pharmaceutics11110590 - 08 Nov 2019
Cited by 6
Abstract
Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the [...] Read more.
Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
A Combinatorial Cell and Drug Delivery Strategy for Huntington’s Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells
Pharmaceutics 2019, 11(10), 526; https://doi.org/10.3390/pharmaceutics11100526 - 12 Oct 2019
Cited by 2
Abstract
For Huntington’s disease (HD) cell-based therapy, the transplanted cells are required to be committed to a neuronal cell lineage, survive and maintain this phenotype to ensure their safe transplantation in the brain. We first investigated the role of RE-1 silencing transcription factor (REST) [...] Read more.
For Huntington’s disease (HD) cell-based therapy, the transplanted cells are required to be committed to a neuronal cell lineage, survive and maintain this phenotype to ensure their safe transplantation in the brain. We first investigated the role of RE-1 silencing transcription factor (REST) inhibition using siRNA in the GABAergic differentiation of marrow-isolated adult multilineage inducible (MIAMI) cells, a subpopulation of MSCs. We further combined these cells to laminin-coated poly(lactic-co-glycolic acid) PLGA pharmacologically active microcarriers (PAMs) delivering BDNF in a controlled fashion to stimulate the survival and maintain the differentiation of the cells. The PAMs/cells complexes were then transplanted in an ex vivo model of HD. Using Sonic Hedgehog (SHH) and siREST, we obtained GABAergic progenitors/neuronal-like cells, which were able to secrete HGF, SDF1 VEGFa and BDNF, of importance for HD. GABA-like progenitors adhered to PAMs increased their mRNA expression of NGF/VEGFa as well as their secretion of PIGF-1, which can enhance reparative angiogenesis. In our ex vivo model of HD, they were successfully transplanted while attached to PAMs and were able to survive and maintain this GABAergic neuronal phenotype. Together, our results may pave the way for future research that could improve the success of cell-based therapy for HDs. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Effect of Size and Concentration of PLGA-PEG Nanoparticles on Activation and Aggregation of Washed Human Platelets
Pharmaceutics 2019, 11(10), 514; https://doi.org/10.3390/pharmaceutics11100514 - 04 Oct 2019
Cited by 2
Abstract
Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and [...] Read more.
Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and blood constituents, presenting possible safety risks. While NPs investigated are predominantly based on the biodegradable, biocompatible, and FDA approved poly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been reported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined. The aims of this study were to determine the impact of size-selected PLGA-PEG (PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three average sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0–2.2 mg/mL on the activation and aggregation of washed human platelets (WP) was examined. The results of this study show, for the first time, NPs of all sizes associated with the surface of platelets, with >50% binding, leading to possible internalisation. The NP-platelet interaction, however, did not lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The outcome of this study is promising, suggesting that these NPs could be potential carriers for targeted drug delivery to platelets. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Theranostic Sorafenib-Loaded Polymeric Nanocarriers Manufactured by Enhanced Gadolinium Conjugation Techniques
Pharmaceutics 2019, 11(10), 489; https://doi.org/10.3390/pharmaceutics11100489 - 23 Sep 2019
Cited by 4
Abstract
Today, efficient delivery of sorafenib to hepatocellular carcinoma remains a challenge for current drug formulation strategies. Incorporating the lipophilic molecule into biocompatible and biodegradable theranostic nanocarriers has great potential for improving the efficacy and safety of cancer therapy. In the present study, three [...] Read more.
Today, efficient delivery of sorafenib to hepatocellular carcinoma remains a challenge for current drug formulation strategies. Incorporating the lipophilic molecule into biocompatible and biodegradable theranostic nanocarriers has great potential for improving the efficacy and safety of cancer therapy. In the present study, three different technologies for the encapsulation of sorafenib into poly(d,l-lactide-co-glycolide) and polyethylene glycol-poly(d,l-lactide-co-glycolide) copolymers were compared. The particles ranged in size between 220 and 240 nm, with encapsulation efficiencies from 76.1 ± 1.7% to 69.1 ± 10.1%. A remarkable maximum drug load of approximately 9.0% was achieved. Finally, a gadolinium complex was covalently attached to the nanoparticle surface, transforming the nanospheres into theranostic devices, allowing their localization using magnetic resonance imaging. The manufacture of sorafenib-loaded nanoparticles alongside the functionalization of the particle surface with gadolinium complexes resulted in a highly efficacious nanodelivery system which exhibited a strong magnetic resonance imaging signal, optimal stability features, and a sustained release profile. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection
Pharmaceutics 2019, 11(8), 419; https://doi.org/10.3390/pharmaceutics11080419 - 19 Aug 2019
Cited by 2
Abstract
A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into [...] Read more.
A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.®), or even 7.2 μm-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with <50% systemic exposure compared to that with the marketed product. The novel MS was physicochemically stable, with no changes in drug crystallinity and release profile over 12 months. Therefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with osteoarthritis, with reduced IA dosing frequency. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Design and Evaluation of a Poly(Lactide-co-Glycolide)-Based In Situ Film-Forming System for Topical Delivery of Trolamine Salicylate
Pharmaceutics 2019, 11(8), 409; https://doi.org/10.3390/pharmaceutics11080409 - 12 Aug 2019
Cited by 3
Abstract
Trolamine salicylate (TS) is a topical anti-inflammatory analgesic used to treat small joint pain. The topical route is preferred over the oral one owing to gastrointestinal side effects. In this study, a poly(lactide-co-glycolide) (PLGA)-based in situ bio-adhesive film-forming system for the [...] Read more.
Trolamine salicylate (TS) is a topical anti-inflammatory analgesic used to treat small joint pain. The topical route is preferred over the oral one owing to gastrointestinal side effects. In this study, a poly(lactide-co-glycolide) (PLGA)-based in situ bio-adhesive film-forming system for the transdermal delivery of TS was designed and evaluated. Therefore, varying amounts (0%, 5%, 10%, 20%, and 25% (w/w)) of PLGA (EXPANSORB® DLG 50-2A, 50-5A, 50-8A, and 75-5A), ethyl 2-cyanoacrylate, poly (ethylene glycol) 400, and 1% of TS were dissolved together in acetone to form the bio-adhesive polymeric solution. In vitro drug permeation studies were performed on a vertical Franz diffusion cell and dermatomed porcine ear skin to evaluate the distinct formulations. The bio-adhesive polymeric solutions were prepared successfully and formed a thin film upon application in situ. A significantly higher amount of TS was delivered from a formulation containing 20% PLGA (45 ± 4 µg/cm2) and compared to PLGA-free counterpart (0.6 ± 0.2 µg/cm2). Furthermore, the addition of PLGA to the polymer film facilitated an early onset of TS delivery across dermatomed porcine skin. The optimized formulation also enhanced the delivery of TS into and across the skin. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Nanoemulsion Structural Design in Co-Encapsulation of Hybrid Multifunctional Agents: Influence of the Smart PLGA Polymers on the Nanosystem-Enhanced Delivery and Electro-Photodynamic Treatment
Pharmaceutics 2019, 11(8), 405; https://doi.org/10.3390/pharmaceutics11080405 - 11 Aug 2019
Cited by 8
Abstract
In the present study, we examined properties of poly(lactide-co-glycolide) (PLGA)-based nanocarriers (NCs) with various functional or “smart” properties, i.e., coated with PLGA, polyethylene glycolated PLGA (PEG-PLGA), or folic acid-functionalized PLGA (FA-PLGA). NCs were obtained by double emulsion (water-in-oil-in-water) evaporation process, which [...] Read more.
In the present study, we examined properties of poly(lactide-co-glycolide) (PLGA)-based nanocarriers (NCs) with various functional or “smart” properties, i.e., coated with PLGA, polyethylene glycolated PLGA (PEG-PLGA), or folic acid-functionalized PLGA (FA-PLGA). NCs were obtained by double emulsion (water-in-oil-in-water) evaporation process, which is one of the most suitable approaches in nanoemulsion structural design. Nanoemulsion surface engineering allowed us to co-encapsulate a hydrophobic porphyrin photosensitizing dye—verteporfin (VP) in combination with low-dose cisplatin (CisPt)—a hydrophilic cytostatic drug. The composition was tested as a multifunctional and synergistic hybrid agent for bioimaging and anticancer treatment assisted by electroporation on human ovarian cancer SKOV-3 and control hamster ovarian fibroblastoid CHO-K1 cell lines. The diameter of PLGA NCs with different coatings was on average 200 nm, as shown by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. We analyzed the effect of the nanocarrier charge and the polymeric shield variation on the colloidal stability using microelectrophoretic and turbidimetric methods. The cellular internalization and anticancer activity following the electro-photodynamic treatment (EP-PDT) were assessed with confocal microscopy and flow cytometry. Our data show that functionalized PLGA NCs are biocompatible and enable efficient delivery of the hybrid cargo to cancer cells, followed by enhanced killing of cells when supported by EP-PDT. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine
Pharmaceutics 2019, 11(8), 401; https://doi.org/10.3390/pharmaceutics11080401 - 10 Aug 2019
Cited by 3
Abstract
Poly(d,l-lactic-co-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of [...] Read more.
Poly(d,l-lactic-co-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms. Thus, new approaches must be envisaged to target GBM tumour cells potentially providing an efficient treatment. Co-delivery of temozolomide (TMZ) and O6-benzylguanine (O6BG), an inhibitor of DNA repair, could provide good therapeutic outcomes. In this work, a fractional factorial design (FFD) was employed to produce an optimal PLGA-based nanoformulation for the co-loading of both molecules, using a reduced number of observations. The developed NPs exhibited optimal physicochemical properties for brain delivery (dimensions below 200 nm and negative zeta potential), high encapsulation efficiencies (EE) for both drugs, and showed a sustained drug release for several days. Therefore, the use of an FFD allowed for the development of a nanoformulation with optimal properties for the co-delivery of TMZ and O6BG to the brain. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment
Pharmaceutics 2019, 11(8), 392; https://doi.org/10.3390/pharmaceutics11080392 - 05 Aug 2019
Cited by 3
Abstract
Colorectal cancer (CRC) is one of the most malignant and fatal cancers worldwide. Although cytoreductive surgery combined with chemotherapy is considered a promising therapy, peritoneal adhesion causes further complications after surgery. In this study, oxaliplatin-loaded Poly-(d,l-lactide-co-glycolide) (PLGA) microparticles were [...] Read more.
Colorectal cancer (CRC) is one of the most malignant and fatal cancers worldwide. Although cytoreductive surgery combined with chemotherapy is considered a promising therapy, peritoneal adhesion causes further complications after surgery. In this study, oxaliplatin-loaded Poly-(d,l-lactide-co-glycolide) (PLGA) microparticles were prepared using a double emulsion method and loaded into hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based cross-linked (HC) hydrogels. From characterization and evaluation study PLGA microparticles showed smaller particle size with higher entrapment efficiency, approximately 1100.4 ± 257.7 nm and 77.9 ± 2.8%, respectively. In addition, microparticle-loaded hydrogels showed more sustained drug release compared to the unloaded microparticles. Moreover, in an in vivo pharmacokinetic study after intraperitoneal administration in rats, a significant improvement in the bioavailability and the mean residence time of the microparticle-loaded hydrogels was observed. In HC21 hydrogels, AUC0–48h, Cmax, and Tmax were 16012.12 ± 188.75 ng·h/mL, 528.75 ± 144.50 ng/mL, and 1.5 h, respectively. Furthermore, experimental observation revealed that the hydrogel samples effectively protected injured tissues from peritoneal adhesion. Therefore, the results of the current pharmacokinetic study together with our previous report of the in vivo anti-adhesion efficacy of HC hydrogels demonstrated that the PLGA microparticle-loaded hydrogels offer novel therapeutic strategy for CRC treatment. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration
Pharmaceutics 2019, 11(8), 388; https://doi.org/10.3390/pharmaceutics11080388 - 03 Aug 2019
Cited by 3
Abstract
Nanoparticles (NPs) based on the polymer poly (lactide-co-glycolide) acid (PLGA) have been widely studied in developing delivery systems for drugs and therapeutic biomolecules, due to the biocompatible and biodegradable properties of the PLGA. In this work, a synthesis method for bone morphogenetic protein [...] Read more.
Nanoparticles (NPs) based on the polymer poly (lactide-co-glycolide) acid (PLGA) have been widely studied in developing delivery systems for drugs and therapeutic biomolecules, due to the biocompatible and biodegradable properties of the PLGA. In this work, a synthesis method for bone morphogenetic protein (BMP-2)-loaded PLGA NPs was developed and optimized, in order to carry out and control the release of BMP-2, based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. The polymeric surfactant Pluronic F68 was used in the synthesis procedure, as it is known to have an effect on the reduction of the size of the NPs, the enhancement of their stability, and the protection of the encapsulated biomolecule. Spherical solid polymeric NPs were synthesized, showing a reproducible multimodal size distribution, with diameters between 100 and 500 nm. This size range appears to allow the protein to act on the cell surface and at the cytoplasm level. The effect of carrying BMP-2 co-adsorbed with bovine serum albumin on the NP surface was analyzed. The colloidal properties of these systems (morphology by SEM, hydrodynamic size, electrophoretic mobility, temporal stability, protein encapsulation, and short-term release profile) were studied. The effect of both BMP2-loaded NPs on the proliferation, migration, and osteogenic differentiation of mesenchymal stromal cells from human alveolar bone (ABSC) was also analyzed in vitro. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Vitamin E-Loaded PLA- and PLGA-Based Core-Shell Nanoparticles: Synthesis, Structure Optimization and Controlled Drug Release
Pharmaceutics 2019, 11(7), 357; https://doi.org/10.3390/pharmaceutics11070357 - 22 Jul 2019
Cited by 6
Abstract
The (±)-α-Tocopherol (TP) with vitamin E activity has been encapsulated into biocompatible poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) carriers, which results in the formation of well-defined nanosized (d ~200–220 nm) core-shell structured particles (NPs) with 15–19% of drug loading (DL%). The [...] Read more.
The (±)-α-Tocopherol (TP) with vitamin E activity has been encapsulated into biocompatible poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) carriers, which results in the formation of well-defined nanosized (d ~200–220 nm) core-shell structured particles (NPs) with 15–19% of drug loading (DL%). The optimal ratios of the polymer carriers, the TP active drug as well as the applied Pluronic F127 (PLUR) non-ionic stabilizing surfactant, have been determined to obtain NPs with a TP core and a polymer shell with high encapsulation efficiency (EE%) (69%). The size and the structure of the prepared core-shell NPs as well as the interaction of the carriers and the PLUR with the TP molecules have been determined by transmission electron microscopy (TEM), dynamic light scattering (DLS), infrared spectroscopy (FT-IR) and turbidity studies, respectively. Moreover, the dissolution of the TP from the polymer NPs has been investigated by spectrophotometric measurements. It was clearly confirmed that increase in the EE% from ca. 70% (PLA/TP) to ca. 88% (PLGA65/TP) results in the controlled release of the hydrophobic TP molecules (7 h, PLA/TP: 34%; PLGA75/TP: 25%; PLGA65/TP: 18%). By replacing the PLA carrier to PLGA, ca. 15% more active substance can be encapsulated in the core (PLA/TP: 65%; PLGA65/TP: 80%). Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Terahertz Spectroscopy: An Investigation of the Structural Dynamics of Freeze-Dried Poly Lactic-co-glycolic Acid Microspheres
Pharmaceutics 2019, 11(6), 291; https://doi.org/10.3390/pharmaceutics11060291 - 20 Jun 2019
Cited by 2
Abstract
Biodegradable poly lactic-co-glycolic acid (PLGA) microspheres can be used to encapsulate peptide and offer a promising drug-delivery vehicle. In this work we investigate the dynamics of PLGA microspheres prepared by freeze-drying and the molecular mobility at lower temperatures leading to the glass transition [...] Read more.
Biodegradable poly lactic-co-glycolic acid (PLGA) microspheres can be used to encapsulate peptide and offer a promising drug-delivery vehicle. In this work we investigate the dynamics of PLGA microspheres prepared by freeze-drying and the molecular mobility at lower temperatures leading to the glass transition temperature, using temperature-variable terahertz time-domain spectroscopy (THz-TDS) experiments. The microspheres were prepared using a water-in-oil-in-water (w/o/w) double-emulsion technique and subsequent freeze-drying of the samples. Physical characterization was performed by morphology measurements, scanning electron microscopy, and helium pycnometry. The THz-TDS data show two distinct transition processes, T g , β in the range of 167–219 K, associated with local motions, and T g , α in the range of 313–330 K, associated with large-scale motions, for the microspheres examined. Using Fourier transform infrared spectroscopy measurements in the mid-infrared, we were able to characterize the interactions between a model polypeptide, exendin-4, and the PLGA copolymer. We observe a relationship between the experimentally determined T g , β and T g , α and free volume and microsphere dynamics. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Open AccessArticle
Photodynamic Therapy of Ovarian Carcinoma Cells with Curcumin-Loaded Biodegradable Polymeric Nanoparticles
Pharmaceutics 2019, 11(6), 282; https://doi.org/10.3390/pharmaceutics11060282 - 15 Jun 2019
Cited by 13
Abstract
Accumulation of photosensitisers in photodynamic therapy in healthy tissues is often the cause of unwanted side effects. Using nanoparticles, improved bioavailability and site-specific drug uptake can be achieved. In this study, curcumin, a natural product with anticancer properties, albeit with poor aqueous solubility, [...] Read more.
Accumulation of photosensitisers in photodynamic therapy in healthy tissues is often the cause of unwanted side effects. Using nanoparticles, improved bioavailability and site-specific drug uptake can be achieved. In this study, curcumin, a natural product with anticancer properties, albeit with poor aqueous solubility, was encapsulated in biodegradable polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-NP). Dynamic light scattering, laser Doppler anemometry and atomic force microscopy were used to characterise the formulations. Using haemolysis, serum stability and activated partial thromboplastin time tests, the biocompatibility of CUR-NP was assessed. Particle uptake and accumulation were determined by confocal laser scanning microscopy. Therapeutic efficacy of the formulation was tested in SK-OV-3 human ovarian adenocarcinoma cells post low level LED irradiation by determining the generation of reactive oxygen species and cytotoxicity. Pharmacologic inhibitors of cellular uptake pathways were used to identify the particle uptake mechanism. CUR-NP exhibited better physicochemical properties such as stability in the presence of light and improved serum stability compared to free curcumin. In addition, the novel nanoformulation facilitated the use of higher amounts of curcumin and showed strong apoptotic effects on tumour cells. Full article
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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