Polymer Poly(lactic-co-glycolic) Acid Research Articles

USP’s characterization of commercial poly(lactic-co-glycolic acid) utilizing SEC-Multi-Angle Light Scattering and Refractive Index techniques via Absolute Method approach

This research focuses on evaluating the data quality and reliability of Size Exclusion Chromatography with Multi-Angle Light Scattering and Refractive Index (SEC-MALS/RI) chromatography in determining molecular weight-related parameters in poly(lactic-co-glycolic) acid (PLGA) polymers. The study utilizes key metrics, particularly percent relative standard deviation (%RSD), to evaluate the precision across different data processing conditions. Exploring baseline selection of the chromatograms reveals that selection of the baseline based on the intrinsic shape of the chromatogram, rather than relying on elution peaks, improves consistency. The study emphasizes the critical role of result fitting in addressing systematic errors and sample heterogeneity, recommending the minima of the elution peak selection range for realistic molecular weight distribution representation. Analysis of light-scattering (LS) detector chromatograms highlights varying effects on different PLGA polymers, emphasizing the need for careful assessment and potential exclusion for precision improvement, especially in the presence of experimental artifacts. Across diverse PLGA polymers, the utilization of different column types, along with considerations such as baseline determination and peak selection, shows minimal variations in Mn, Mw, and polydispersity index (PDI), affirming the consistency of the methodology. The %RSD analysis further supports the methodology's precision, with values well within acceptable limits. In summary, this comprehensive evaluation of methodological conditions, including baseline selection, result fitting, LS detector data management, and column types, establishes a reliable SEC-MALS/RI chromatographic approach by Absolute Method for determining molecular weight parameters in PLGA polymers.

Development of a biodegradable polymer-based implant to release dual drugs for post-operative management of cataract surgery.

Cataract surgery is followed by post-operative eye drops for a duration of 4-6 weeks. The multitude of ocular barriers, coupled with the discomfort experienced by both the patient and their relatives in frequently administering eye drops, significantly undermines patient compliance, ultimately impeding the recovery of the patient. This study aimed to design and develop an ocular drug delivery system as an effort to achieve a drop-free post-operative care after cataract surgery. An implant was prepared containing a biodegradable polymer Poly-lactic-co-glycolic acid (PLGA), Dexamethasone (DEX) as an anti-inflammatory drug, and Moxifloxacin(MOX) as an antibiotic. Implant characterization and drug loading analysis were conducted. In vitro drug release profile showed that the release of the two drugs are correlated with the clinical prescription for post operative eye drops. In vivo study was conducted on New Zealand albino rabbits where one eye underwent cataract surgery, and the drug delivery implant was inserted into the capsular bag after placement of the synthetic intraocular lens (IOL). Borderline increase in the intraocular pressure (IOP) was noted in the test sample group. Slit-lamp observations revealed no significant anterior chamber reaction in all study groups. Histopathology study of the operated eye revealed no significant pathology in the test samples. This work aims at developing the intra ocular drug delivery implant which will replace the post-operative eye drops and help the patient with the post-operative hassle of eye drops.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity

BackgroundWith the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. MethodsLVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. ResultsData revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. ConclusionThese data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Polylactic-Co-glycolic Acid Polymer-Based Nano-Encapsulation Using Recombinant Maltoporin of Aeromonas hydrophila as Potential Vaccine Candidate.

Aquaculture production has been incurring economic losses due to infectious diseases by opportunistic pathogens like Aeromonas hydrophila, a bacterial agent that commonly affects warm water aquacultured fish. Developing an effective vaccine with an appropriate delivery system can elicit an immune response that would be a useful disease management strategy through prevention. The most practical method of administration would be the oral delivery of vaccine developed through nano-biotechnology. In this study, the gene encoding an outer membrane protein, maltoporin, of A. hydrophila, was identified, sequenced, and studied using bioinformatics tools to examine its potential as a vaccine candidate. Using a double emulsion method, the molecule was cloned, over-expressed, and encapsulated in a biodegradable polymer polylactic-co-glycolic acid (PLGA). The immunogenicity of maltoporin was identified through in silico analysis and thus taken up for nanovaccine preparation. The encapsulation efficiency of maltoporin was 63%, with an in vitro release of 55% protein in 48h. The particle size and morphology of the encapsulated protein exhibited properties that could induce stability and function as an effective carrier system to deliver the antigen to the site and trigger immune response. Results show promise that the PLGA-mediated delivery system could be a potential carrier in developing a fish vaccine via oral administration. They provide insight for developing nanovaccine, since sustained in vitro release and biocompatibility were observed. There is further scope to study the immune response and examine the protective immunity induced by the nanoparticle-encapsulated maltoporin by oral delivery to fish.

An insight to development and in-vitro, ex-vivo, in-vivo study of naringenin nanoparticles against letrozole induced polycystic ovarian syndrome in female wistar rats

The biocompatible and biodegradable polymer polylactic-co-glycolic acid (PLGA) 50:50 was used to fabricate Naringenin Nanoparticles. Development of Nanoparticles were optimized by using 32 factorial designs to study the impact of the PLGA concentration and High-pressure homogenizer cycles on the particle size, Polydispersity index (PDI), and % entrapment efficiency (%EE). The optimized batch was examined for several characteristics, including DSC, SEM, in vitro drug release study, etc. Prepared nano-formulation was subjected to assess the animals PCOS induced by the letrozole. To assess the animals for PCOS, letrozole was first given to them. Five groups were created at random: Normal control, Let group (PCOS induced), Naringenin Nanoparticles 50 mg/kg (NAR1), Naringenin Nanoparticles 100 mg/kg (NAR2), Clomiphene citrate 1 mg/kg (Clomi citrate). The expression of SIRT1 and PGC-1α in the ovary was examined using the ELISA technique, as well as alterations to the estrus cycle, body weight, ovarian activity, serum levels of hormones such as testosterone (TTST), estradiol (E), luteinizing hormone (LH), follicle-stimulating hormone (FSH), glucose metabolism, and ovarian function. Additionally, the fecal microbiome's gut makeup was examined. To conclude, naringenin-loaded PLGA nanoparticles (NAR1 and NAR2) showed a protective impact on the concentrations of several sex hormones, the composition of the gut microbiota, as well as on MDA, SOD, and CAT, and GSH levels and avoided the ovarian morphological modification in the letrozole-induced PCOS. The use of NAR1 and NAR2 dispersion is a promising option for PCOS treatment, according to the current study's findings.

Microfabrication and Characterization of Chemically Actuated Implantable PLGA Reservoir-based Device for Controlled Drug Delivery

This paper proposes the fabrication and characterization of the drug delivery device (DDD) that is capable of delivering the drug to the target site using bio-degradable polymer. The insulin used as a model drug in this study was loaded into the microreservoir (5 mm * 5 mm * 0.5 mm) which was fabricated using Poly-Lactic-Co-Glycolic acid (PLGA) polymer. The permeation of the drug solution and the release rates were controlled by varying the thickness of the biodegradable membrane. The fabricated DDD was designed to deliver about 20 µL of the drug. Implantable formulations of insulin were generated using biodegradable polymer PLGA, which were further tested by loading different quantities of the drug. The activity of the implant was tested using in-vitro release by taking Phosphate-buffered saline (PBS), as well as in-vivo pharmacokinetic studies in Wistar rats. Insulin-loaded implants were inserted under the skin layer by minor surgery. The blood samples were collected at different time intervals, which were further analyzed by High-performance liquid chromatography (HPLC). The obtained results confirmed the presence of insulin in the blood by showing a retention time (RT) of 2.8 min at λ max of 280 nm. The results have shown that the insulin was found in the blood after 4 h of implant insertion and remained up to 48 h. This study clearly suggests that the fabricated device can be used for the successful delivery of insulin in the blood. The use of this DDD bypasses the degradation of insulin in the stomach and thus can be used as an effective drug carrier system for the delivery of insulin.

PLGA-The Smart Biocompatible Polimer: Kinetic Degradation Studies and Active Principle Release.

The aim of our research was the development of prolonged delivery systems for therapeutic agents with various properties (prevention and treatment of bone diseases, anti-neoplastic, anti-inflammatory, antioxidant) that would ensure sustained therapeutic levels of the active principle, above the minimum inhibitory concentration, without reaching toxic levels over a long period of time as alternatives to conventional routes of administration. PLGA (poly lactic-co-glycolic acid), a biodegradable and biocompatible synthetic polymer, FDA approved, with a 65:35 lactic acid (LA): glycolic acid (GA) copolymer ratio, was chosen as delivery system. Our studies have shown that in PBS it undergoes two simultaneous degradation processes, hydrolysis and autohydrolysis, degrading completely in about 40 days. The release of the active principle is determined by the diffusion from inside the polymer matrix to the outside, which occurs simultaneously with the erosion of the polymer, during 35 days.

PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases.

Research on the use of biodegradable polymers for drug delivery has been ongoing since they were first used as bioresorbable surgical devices in the 1980s. For tissue engineering and drug delivery, biodegradable polymer poly-lactic-co-glycolic acid (PLGA) has shown enormous promise among all biomaterials. PLGA are a family of FDA-approved biodegradable polymers that are physically strong and highly biocompatible and have been extensively studied as delivery vehicles of drugs, proteins, and macromolecules such as DNA and RNA. PLGA has a wide range of erosion times and mechanical properties that can be modified. Many innovative platforms have been widely studied and created for the development of methods for the controlled delivery of PLGA. In this paper, the various manufacturing processes and characteristics that impact their breakdown and drug release are explored in depth. Besides different PLGA-based nanoparticles, preclinical and clinical applications for different diseases and the PLGA platform types and their scale-up issues will be discussed.

Design and Development of a New Method for the Production of Nanotoxoids from Clostridium Perfringens Beta Toxin.

In recent years, a nanoparticle-based strategy has shown that non-denatured protein toxins can be used to enhance the appropriate immune response. Once the toxin reacts between the nanoparticles and the protein (toxin), it loses its toxicity because it does not attach to its ligand at the cell surface. The results of the nanoparticle and toxin complex show that the nanoparticles facilitate the internal release of the toxin. Clostridium perfringens beta toxin is produced by Clostridium perfringens type B and C, and diarrhea is the most important disease caused in newborn lambs. When beta toxin forms a complex with nanoparticles, the reaction between the toxin and the nanoparticle leads to the formation of a new form of nanoparticle in which the toxin loses its lethality due to its involvement; therefore, it becomes a toxoid. The nanoparticles used in this research are of poly lactic-co-glycolic acid (PLGA) type, one of the most developed biodegradable polymers. This study aimed to isolate and purify Clostridium perfringens beta toxin and produce its complex with PLGA nanoparticles to form a non-toxic structure. In this study, Clostridium perfringens beta toxin type B was isolated using ammonium sulfate precipitation and gel filtration chromatography. Toxin assay was performed in vivo (lethal dose [LD50]) and in vitro by sodium dodecyl sulphate-polyacrylamide gel electrophoresis at each stage, and the quantity of purified toxin was calculated to be 10 mg/ml. Afterward, the beta toxin antigen was used as the basis for the preparation of nanotoxoid candidates with nanoparticle formulation. Moreover, the PLGA polymer and water-oil-water methods were used to fabricate nanoparticles. Under optimal conditions, nanoparticles without antigen with an average size of 100 nm and zeta potential of -23.28 mV, as well as nanoparticles containing antigen with an average size of 120 nm and zeta potential of -18.2 mV, were prepared. When nanoparticles are injected into mice with the beta toxin, the toxin becomes a toxoid with no toxicity effects, and it cannot bind to its receptors and reveal its effects. In this study, the mice showed mild symptoms in one case, and none of them died. The beta and PLGA toxin model could also be applied as a candidate to study the release and immunization of the target animal. In order to achieve antigen regulation using natural polymers, it is recommended to conduct a comparative study between nanoparticles based on natural polymers.

Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice.

Poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation. We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice. RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes' expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test. These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.

Development and Evaluation of Icariin-Loaded PLGA-PEG Nanoparticles for Potentiation the Proapoptotic Activity in Pancreatic Cancer Cells.

Therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, towards improvement of anticancer potential of icariin (ICA) on pancreatic cancer, the drug was entrapped into the polymeric poly lactic-co-glycolic acid (PLGA) with polyethylene glycol (PEG) as diblock copolymer. Optimization of the formulation was done using Statgraphics software to standardize percentages of PEG-PLGA and tween 80 (TW80) to obtain the smallest particle size. The optimized formulation was found to be in nanometer size and low PDI (0.321). Optimized formula enhanced cytotoxicity and apoptotic potential, compared with ICA-raw, against pancreatic cancer cell lines (aspc-1). The entrapment efficiency of the polymeric micelles was 72.34 ± 2.3% with 93.1 ± 6.5% release of ICA within 72h. There was a twofold increase in apoptosis and sevenfold increase in necrosis of aspc-1 cells when incubated with raw ICA compared to control cells. Further, loss of mitochondrial membrane potential (⁓50-fold) by the ICA-loaded PMs and free drug compared to control cells was found to be due to the generation of ROS. Findings of cell cycle analysis revealed the significant arrest of G2-M phase of aspc-1 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-3 established the superiority of the PMs approach against pancreatic cancer. In summary, the acquired results highlighted the potentiality of PMs delivery tool for controlling the growth of pancreatic cancer cells for improved efficacy.

Drug Release Studies of SC-514 PLGA Nanoparticles

A major problem associated with prostate cancer treatment is the development of drug resistance. The development of drug resistance often leads to prostate cancer metastasis and prostate cancer-targeted drug delivery systems can be utilized to address this problem. Traditional drug delivery systems have many challenges, including the inability to control the drug release rate, target site inaccuracy, susceptibility to the microenvironment, poor drug solubility, and cytotoxicity of chemotherapeutics to non-malignant cells. As a result, there is an urgent need to formulate and functionalize a drug delivery system that better controls drug release. This study was designed to quantify the release of SC-514 from SC-514 Polylactic-Co-Glycolic Acid (PLGA) nanoparticles and conjugate SC-514-PLGA coated nanoparticles with the NF- κβ antibody, as well as fats. This study further explored new methods to quantify the release of SC-514 drug from the SC-514-PLGA coated nanoparticles after utilizing Liquid Chromatography–Mass Spectrometry (LC-MS) as the standard method to quantify SC-514 drug released. After quantification was completed, cell viability studies indicated that the ligand conjugated nanoparticles demonstrated a considerable ability to reduce tumor growth and SC-514 drug toxicity in the PC-3 cell line. The prepared drug delivery systems also possessed a significantly lower toxicity (P<0.05), bettered controlled-release behaviors in prostate cancer, and increased the solubility of SC-514 in comparison to free SC-514. SC-514 released from SC-514-PLGA, SC-514-PLGA-NF- κβAb, and SC-514-PLGA-Fat nanoparticles, significantly inhibited tumor growth when compared to that of free SC-514. The anti-cancer therapeutic effects of SC-514 were improved through the encapsulation of SC-514 with a PLGA polymer. The functionalized SC-514-PLGA nanoparticles can further control burst release. The new methods utilized in this study for quantifying drug release, may prove to be as effective as the current standard methods, such as LC/MS.

Drug Release Studies of SC‐514 PLGA Nanoparticles

Background A major problem associated with prostate cancer treatment is drug resistance leading to prostate cancer metastasis. Prostate cancer-targeted drug delivery system is one way to address this problem. Traditional drug delivery systems face many challenges, such as inability to control the release rate, inaccurate targeting, susceptibility to the microenvironment, and poor stability of the drug. Hence, there is a need to formulate a drug delivery system and functionalize the surface of delivery system for a better control of drug release. Targeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. This study was designed to measure drug release of SC-514-PLGA nanoparticles and conjugate SC-514 polylactic-co-glycolic acid (PLGA) nanoparticles loaded with NF-KB antibody and fats. This study explored new methods to quantify the SC-514 drug released from SC-514-PLGA nanoparticles. The anti-proliferative effects of the SC-514 drug released by the nanoparticle treatments were investigated in PC-3 cells and cord blood cells. MDR expression in PC-3 cells was investigated after treatment with free SC-514 and SC-514 from SC-514-PLGA nanoparticles. Methods SC-514drug release was studied under in vitro conditions in phosphate buffer solution (PBS) at a pH of 7.4, using dialysis method. Liquid chromatography–mass spectrometry (LC-MS) was utilized as the standard method to quantify SC-514 drug released. Furthermore, other experimental methods utilized to quantify SC-514 drug released included: colony assay, wound healing assay, and transwell migration and invasion assays. MTT calorimetric assay was utilized to investigate the impact of the nanoparticle formulations (SC-514-PLGA, SC-514-PLGA-NF-KB, SC-514-PLGA-Fat) on PC-3 cells and cord blood cells. In addition, in vitro cellular uptake of fluorescent nanoparticle formulations in PC-3 and cord blood cells were examined with confocal fluorescence microscope. Results The ligand conjugated nanoparticles showed considerable reduction of tumor growth and toxicity (side-effect of the drug treatment in prostate cancer) of SC-514 drug in prostate cancer treatment. Our results demonstrated that prepared drug delivery system possesses a much lower toxicity, better prostate cancer controlled-release behaviors and confers higher solubility to SC-514 than free SC-514. SC-514 released from SC-514-PLGA, PLGA-SC-514-NF-KB, and PLGA-SC-514-Fat significantly inhibited tumor growth when compared to free SC-514. A more significant reduction of cell viability was recorded in PC-3 cells by all treatments (Free SC-514, SC-514-PLGA, and SC-514-PLGA-NF-KB) compared to cord blood cells, except for SC-514-PLGA-Fat nanoparticle formulation.SC-514 drug from SC-514-PLGA nanoparticles reduced the expression of MDR proteins than free SC-514. Conclusion Encapsulation of SC-514 with PLGA polymer increased the anti-cancer therapeutic effects of SC-514 drug. Burst release from SC-514-PLGA nanoparticles can be controlled by functionalization. New methods of quantifying drug release maybe as effective as the standard methods of drug quantification, such as LC/MS method.

Fabrication and Evaluation of Transdermal Microneedles for a Recombinant Human Keratinocyte Growth Factor.

Microneedle transdermal patches are a combination of hypodermic needles and transdermal patches used to overcome the individual limitations of both injections and patches. The objective of this study was to design a minimally invasive, biodegradable polymeric recombinant human keratinocyte growth factor (rHuKGF) microneedle array and evaluate the prepared biodegradable microneedles using in vitro techniques. Biodegradable polymeric microneedle arrays were fabricated out of poly lactic-co-glycolic acid (PLGA) using the micromolding technique under aseptic conditions, and the morphology of the microneedles was characterized using light microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to rule out drug-polymer interactions. Standard procedures were used to analyze the prepared microneedle arrays for in vitro drug release and to perform a microneedle insertion test. Enzyme-linked immunosorbent assay was used to quantify rHuKGF. The PLGA polymer was safe for use in the fabrication of rHuKGF microneedles as there was no interaction between the drug and the polymer. The fabricated rHuKGF microneedle arrays had fully formed microneedles with a height of 600 µm and a base of 300 µm. The drug from the microneedle patch was released in vitro within 30 minutes. The strength of the microneedles in the patch was good, as they were able to reach a depth of 381±3.56 µm into parafilm without any structural change or fracture. Microneedle transdermal patches were successfully prepared for rHuKGF, and their evaluation suggested excellent quality and uniformity of patch characteristics. This can have potential applications in the therapeutic arena, offering advantages in terms of reduced dosing frequency, improved patient compliance, and bioavailability.

Electronic, mechanical and thermal properties of SiO2 nanotube interacting with poly lactic-co-glycolic acid: Density functional theory and molecular dynamics studies

For the first time in this work, computational investigations using density functional theory (DFT) were employed to figure out the interaction of the Poly lactic-co-glycolic acid (PLGA) monomer with Carbon nanotube (CNT) and SiO2 nanotube (SiO2NT). The DFT method was used to calculate the binding energy between the PLGA monomer and these nanotubes for the most stable configuration. The achieved results demonstrate that PLGA monomer chemisorbed onto the surface of SiO2NT (Eb=-1.11eV). In contrast, the nature of interaction for the CNT (Eb=-0.27eV) complex is physisorption and the PLGA monomer interacts with CNT through non-covalent interaction. The findings display that the interaction between PLGA and SiO2NT, owing to the smaller equilibrium interval and superior binding energy is more potent than CNT. Furthermore, the electronic properties of the most stable configuration were evaluated by computing the electronic density of state (DOS). Afterward, the mechanical properties of the SiO2NT, PLGA polymer chains, and PLGA/SiO2NT nanocomposite were studied by Molecular Dynamics (MD) simulations. The Universal, Dreiding, and COMPASS force fields were utilized to compute Young’s modulus, bulk, and shear moduli of these configurations. The obtained results indicate that the interaction of PLGA with SiO2NT surface rises Young’s modulus and shear and bulk moduli of PLGA. As a result, the inclusion of SiO2NT to the PLGA polymer matrix increase PLGA mechanical properties. We have also studied the influence of temperature on the mechanical properties of PLGA nanocomposite. The results revealed that the Young modulus of PLGA nanocomposite reduces by increasing the temperature. The outcomes of the present investigation could be precious for scholars to discover the potential uses of the PLGA nanocomposite in the bio-medical field ranging from bone tissue engineering to drug delivery.

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells.

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8–145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from −17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

Spectrin conjugated PLGA nanoparticles for potential membrane phospholipid interactions: Development, optimization and in vitro studies

The distorted membrane asymmetry and abnormal distribution of phospholipids viz., phosphatidylserine (PS), and phosphatidylethanolamine (PE) in the outer leaflet are critical features of cancer. In the present study, the blood protein spectrin (SPN) was used as a ligand due to it PS-binding affinity and drug nisin was used because it disrupts and fluidized the plasma membrane. Polymeric poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared and optimized by the Response surface Box Behnken randomized model using various independent and dependent variables. The optimized-nanoparticles (NNP2) were further conjugated with SPN, and conjugation was confirmed by infrared spectroscopy, and in silico docking, the analysis was also conducted for the ligand-polymer interactions. Both nanoparticulate formulations were further characterized for mean particle size, drug entrapment, zeta potential, surface morphology, and in vitro drug release and kinetic study. The results indicated that the prepared formulations were in spherical, nano-metric size with –ve zeta potential. More than 64% drug entrapment with 85% drug released after 72 h were found in both types of formulations. In vitro cytotoxicity study was performed by sulforhodamine blue assay on MDA-MB-231 (breast cancer), and FR-2 (normal breast epithelial) cell lines and results showed the IC50 of unconjugated and SPN-conjugated nanoparticles 13.0 μg/mL and 0.06 μg/mL, respectively on MDA-MB-231 whereas 276.11 μg/mL and 142.99 μg/mL on FR-2. Briefly, results suggest that the developed nanoparticles could be used for better cancer treatment without any harmful effects on adjacent normal cells.

Release kinetics of fluorescent dyes from PLGA nanoparticles in retinal blood vessels: In vivo monitoring and ex vivo localization

PLGA (poly(lactic-co-glycolic acid))-based nanoparticles (NPs) are promising drug carrier systems because of their excellent biocompatibility and ability for sustained drug release. However, it is not well understood how the kinetics of such drug delivery system perform in the retinal blood circulation as imaged in vivo and in real time. To answer this question, PLGA NPs were loaded either with lipophilic carbocyanine perchlorate (DiI) or hydrophilic Rhodamine 123 (Rho123) and coated with poloxamer 188 (P188): PLGA-DiI/P188 and PLGA-Rho123/P188. All particles had narrow size distributions around 130 nm, spherical shape and negative potential. Subsequently, we performed in vivo real-time imaging of retinal blood vessels, combined with ex vivo microscopy to monitor the kinetics and to detect location of those two fluorescent markers. We found that DiI signals were long lasting, detectable >90 min in blood vessels after intravenous injection as visible by homogeneous labelling of the vessel wall as well as by spots in the lumen of blood vessels. In contrast, Rho123 signals mostly disappeared after 15 min post intravenous injection in such compartment. To explore how PLGA NP-loaded cargoes are released in the retina in vivo, we thereafter monitored the Cyanine5.5 amine (Cy5.5) covalently linked PLGA polymer (Cy5.5-PLGA) in parallel to DiI and Rho123. The Cy5.5 signal from PLGA polymer was detectable in the retina vessels >90 min for both, the Cy5.5-PLGA-DiI/P188 and Cy5.5-PLGA-Rho123/P188 groups. Microscopy of the ex vivo retina tissue revealed partial level of colocalization of PLGA with DiI but no colocalization between PLGA and Rho123 at 2 h post injection. This indicates that at least a fraction of the lipophilic DiI was preserved within NPs, whereas no hydrophilic Rho123 was associated with NPs at that time point. In conclusion, the properties of PLGA carrier-cargo system in the blood circulation of the retina might be strongly influenced by the combination of factors, including the individual properties of loaded compounds and blood milieu. Thus, it is unlikely that a single nanoparticle formulation will be identified that is universally effective for the delivery of different compounds.

Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation.

The development of antifibrotic materials and coatings that can resist the foreign body response (FBR) continues to present a major hurdle in the advancement of current and next-generation implantable medical devices, biosensors, and cell therapies. From an implant perspective, the most important issue associated with the FBR is the prolonged inflammatory response leading to a collagenous capsule that ultimately blocks mass transport and communication between the implant and the surrounding tissue. Up to now, most attempts to reduce the capsule thickness have focused on providing surface coatings that reduce protein fouling and cell attachment. Here, we present an approach that is based on the sustained release of a peptide drug interfering with the FBR. In this study, the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) was used as a coating releasing the relaxin peptide analogue B7-33, which has been demonstrated to reduce organ fibrosis in animal models. While in vitro protein quantification was used to demonstrate controlled release of the antifibrotic peptide B7-33 from PLGA coatings, an in vitro reporter cell assay was used to demonstrate that B7-33 retains activity against the relaxin family peptide receptor 1 (RXFP1). Subcutaneous implantation of PLGA-coated polypropylene samples in mice with and without the peptide demonstrated a marked reduction in capsule thickness (49.2%) over a 6 week period. It is expected that this novel approach will open the door to a range of new and improved implantable medical devices.

Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.