Loaded Polycaprolactone Nanoparticles Research Articles

Formulation and evaluation of the vascular endothelial growth factor loaded polycaprolactone nanoparticles

In an attempt to increase molecular stability and provide controlled release, vascular endothelial growth factor (VEGF) was encapsulated into polycaprolactone (PCL) nanoparticles. Both VEGF-free and VEGF-loaded PCL nanoparticles were formulated by w/o/w double emulsion of the dichloromethane-water system in the presence of polyvinyl alcohol (PVA) and rat serum albumin. To achieve the optimal formulation concerning particle size and monodispersity, studies were carried out with different formulation parameters, including PVA concentration, homogenization time and rate. Scanning electron microscopy and dynamic light scattering analysis showed respectively that particles had a spherical shape with a smooth surface and particle size varying between 58.68-751.9 nm. All of the formulations were negatively charged according to zeta potential analysis. In vitro release study was performed in pH 7.4 phosphate-buffered saline at 37°C and released VEGF amount was measured by enzyme-linked immunosorbent assay (ELISA) method. At the end of the 35th day, 10% of total encapsulated VEGF was released with a sustained-release profile, which fitted the Korsmeyer-Peppas kinetic model. The bioactivation of the nanoparticles was evaluated using XTT and ELISA methods. As a result, the released VEGF was biologically active and also VEGF loaded PCL nanoparticles enhanced proliferation of the human umbilical vein endothelial cells in cell culture.

Combination of Daratumumab and Doxorubicin Loaded Polycaprolactone Nanoparticles in the Treatment of Diffuse Large B-cell Lymphoma

Combination of Daratumumab and Doxorubicin Loaded Polycaprolactone Nanoparticles in the Treatment of Diffuse Large B-cell Lymphoma

Effect of Cisplatin/Curcumin-Loaded Polycaprolactone Nanoparticles on Oral Carcinoma Cells

This work aimed to investigate the effect of cisplatin (CDDP)/curcumin (Cur)-loaded polycaprolactone nanoparticles (PCL-NPs) on an oral epidermal carcinoma cell line. PCL-NPs were fabricated using nanoprecipitation method employing poly(vinyl alcohol) and polysorbate 80 as stabilizers. Two anticancer compounds, CDDP and Cur, were incorporated into the PCL-NPs by entrapment technique. The physical characteristics of the NPs were evaluated. The presence of the drugs on the NPs was ascertained using Attenuated total reflection Fourier-transformed infrared (ATR-FTIR) spectroscopy, and the drug content was quantified by indirect method using ultraviolet spectroscopy and inductive coupled plasma-mass spectroscopy. The cytotoxic effect was demonstrated using MTT assay and the synergistic effect of both drugs was calculated by the combination index method using CompuSyn® software. The findings revealed that the PCL-NPs were less than 300 nm with narrow size distribution. The appropriate drug concentration for drug loading was 0.12 mg/mL of Cur and 0.02 mg/mL of CDDP, providing approximately 70% and 80% loading efficacy, respectively. The improved anticancer effect was observed in the cells treated with mixture of the drugs and the NPs loaded with dual drugs. Above all, CDDP/Cur-loaded PCL-NPs were successfully prepared. The delivery system exhibited good anticancer effect against oral cancer cells which may be attributed to the synergism effect of CDDP and Cur loaded on the NPs.

Fabrication and characterization of injectable thermosensitive hydrogel containing dipyridamole loaded polycaprolactone nanoparticles for bone tissue engineering

Entrapping osteogenic agents in in-situ forming scaffolds is an effective strategy to promote bone repair. In this study, thermo-sensitive chitosan (CS)/Silk fibroin (SF) hydrogels associated with dipyridamole (DIP) loaded polycaprolactone nanoparticles (DIP-PCL NPs) were prepared for the localized controlled delivery of DIP. DIP-PCL NPs were prepared using the solvent-emulsification evaporation method and the effects of different formulation variables on the properties of NPs were evaluated using the irregular factorial design. Then, the optimized NPs were dispersed into the in-situ gel and characterized for the in-vitro gelation time, pH, mechanical properties, and rheological properties. The optimized DIP-PCL NPs showed the particle size of 349.53 ± 8.20 nm, the polydispersity index of 0.34 ± 0.12, the zeta potential of −1.89 ± 0.10 mV, drug loading of 26.25 ± 0.37%, the encapsulation efficiency of 89.20 ± 0.49% and the release efficiency of 30.04 ± 1.49%. Among various prepared hydrogel systems, the hydrogel composed of 2% (w/v) CS with 0.5% (w/v) ß-glycerophosphate and 0.5% (w/v) SF showed the minimum gelation time and the highest mechanical strength. In-vitro release study also showed that DIP could be sustained released from the system. Cell culture study also revealed that the proliferation and differentiation of the cells treated with the DIP-PCL NPs -CS2/SF0.5 hydrogel were higher than those treated with DIP-PCL NPs at all-time intervals. The superior performance of the DIP-PCL- CS2/SF0.5 hydrogel indicated that this system could be useful for bone tissue engineering.

Design of multicomponent indomethacin-paracetamol and famotidine loaded nanoparticles for sustained and effective anti-inflammatory therapy.

Indomethacin is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) that are widely prescribed drug for pain and inflammation. However, its notoriety of causing gastrointestinal effect, low water solubility, and its short half-life would affect patient compliance and its oral absorption and accordingly justify the need to develop a formula with a controlled and sustained release manner in combination with anti-ulcer drugs. Herein, we synthesized indomethacin-paracetamol co-drug loaded in nanoemulsion and encapsulated in famotiditine loaded polycaprolactone (PCL) nanoparticles. The synthesis of the co-drug was achieved by the formation of a hydrolyzable ester between the indomethacin and paracetamol. The synthesized co-drug was preloading in nanoemulsion (Co-NE), which encapsulated into famotidine PCL nanoparticles utilizing the nanoprecipitation approach. The developed nanosystem showed hydrodynamic size less than 200 nm and the zeta potential value above -30 mV. TEM images confirmed the morphological structure of the formed nanoemulsion and the loaded PCL nanoparticles. Stability studies revealed that the developed nanosystem was stable at different temperatures and pHs over 1 month. Moreover, improvement of the solubilities of these three drugs leading to have a controlled-release multicomponent system of both co-drug and famotidine over 3 days. This multicomponent nanoparticle might be a potential platform to overcome the obstacles of NSAIDs, synergize drugs with different mechanisms of actions by co-encapsulating a small-sized nanoemulsion into PCL nanoparticles for reaching the goal of effective anti-inflammatory therapy.

The Trigeminal Pathway Dominates the Nose-to-Brain Transportation of Intact Polymeric Nanoparticles: Evidence from Aggregation-Caused Quenching Probes.

Nasal drug delivery is a fascinating approach to bypass the blood-brain barrier, which instead directly transports drug molecules to the brain from the nasal cavity along the olfactory and trigeminal nerves. However, the feasibility of nose-to-brain transportation of intact nanoparticles and the possible corresponding pathways remain poorly understood. The purpose of the present study is to explore the intranasal fate of curcumin (Cur)-loaded polycaprolactone nanoparticles (PCL NPs) via fluorescent bioimaging strategies. The behavior of intact nanoparticles was tracked by aggregation-caused quenching (ACQ) probes, which provide on-to-off fluorescent switching from loaded to released states. Evidence for the translocation of intact nanoparticles and Cur was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Intact PCL NPs, irrespective of whether or not they are PEGylated, cannot enter into the olfactory bulb from the nasal cavity, whereas free Cur molecules that are released from the nanoparticles can diffuse into the olfactory bulb. Both PCL NPs and PEGylated PCL NPs carrying Cur can permeate into the mucosa and the trigeminal nerves. Although PEGylation improves the nasal retention of NPs and mucus-penetration, it reduces permeation of NPs into the trigeminal nerves. Transportation of NPs along the trigeminal nerves is slow. Neither the carriers nor the Cur signals are found in the brain at 1 h post-administration. However, starting at 2 h post-administration, both intact nanoparticles and Cur are transported into the brainstem, as exemplified by the presence of Cur-loaded PEGylated PCL NPs. Nanoparticles reaching the brainstem can further distribute to other parts of the brain such as the middle brain. We conclude that the trigeminal nerve pathway, instead of the olfactory nerve route, dominates the nose-to-brain delivery of intact polymeric nanoparticles.

DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model

The purpose of present investigation was to nano-encapsulate atypical antipsychotic such as Olanzapine in polymeric nanoparticles in order to explore the possibility of minimizing drug associated extrapyramidal adverse effects. The polymeric nanoparticulate systems were prepared using FDA approved polymer, polycaprolactone, by simple technique of nanoprecipitation using factorial design by DoE approach. The significant factors selected for the optimization during formulation development process were polymer content and surfactant concentration at three different levels (32 factorial design). The effect of selected significant factors were studied in depth on significant responses such as particle size and encapsulation efficiency. The optimized formulation was further surface modified with surfactant (polysorbate 80) so as to enhance the brain targeting efficiency of developed nanoparticles via endocytosis pathway. Furthermore, catalepsy was induced in rodent model and the designed formulations were investigated in comparison with pure drug solution for efficiency in decreasing extrapyramidal adverse effects. The results of in vitro characterization studies demonstrated a narrow size distributed nanoparticles (73.28 ± 2.14 nm) with high stability indicating zetapotential (−32.46 ± 1.15 mV) and high encapsulation efficiency (78.77 ± 2.83%). In vitro release studies resulted in an extended release of atypical antipsychotic for 60 h from drug-loaded optimized nanoparticulate formulations. The catalepsy studies in rodent model demonstrated a significant decrease in extra pyramidal adverse effects as compared to the pure atypical antipsychotic. Thus, the designed antipsychotic loaded polymeric nanoparticulate system may be highly promising for the tremendous improvement of antipsychotic therapy with reduced adverse effects.

NANOENCAPSULATION AUGMENTS RELEASE EFFICACY AND GLUCOSE TOLERANCE OF 14-DEOXY, 11, 12-DIDEHYDRO ANDROGRAPHOLIDE LOADED POLYCAPROLACTONE NANOPARTICLES IN STREPTOZOTOCIN-NICOTINAMIDE INDUCED TYPE 2 DIABETES

Objective: This study was designed to study the release efficacy and glucose tolerance of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles in streptozotocin-nicotinamide induced type 2 diabetes.Methods: Biodegradable polymer based novel drug delivery systems had brought a considerable attention to improve therapeutic efficacy and bioavailability of various drugs. In this study, 14-deoxy-11, 12-didehydroandrographolide (sparingly water soluble) loaded polycaprolactone (nano-DDA) was synthesized using polyvinyl alcohol and tween20 as surfactants. MTT assay was performed to analyse the cytotoxicity of both the formulations on L6 myoblasts. Free DDA and nano-DDA were administered orally to the streptozotocin-nicotinamide induced experimental diabetic rats for 45d. Oral glucose tolerance test (OGTT) was carried out at the end of the study. After one week washout period, animals were administered with free and nano-DDA and release efficacy of DDA from polymer matrix and concentration of glucose were analysed.Results: MTT assay revealed that nano-DDA prepared using tween-20 as a surfactant elicited cytotoxicity towards L6 myoblasts, whereas nano-DDA prepared using polyvinyl alcohol as a surfactant remained non-toxic till 10µM. OGTT studies revealed an initial increase of glucose at 30 min followed by a progressive decrease in the glucose level. In rat plasma, a gradual decrease in glucose level was observed up to 32h (139 mg/dl) for free DDA, whereas nano-DDA exhibited a major decrease in glucose concentration at 32h (115 mg/dl) which continued even after 48h (117 mg/dl).Conclusion: A slow and sustained release of DDA from the polymer matrix substantiated that nanoencapsulation enhanced the oral bioavailability of DDA which resulted in decreasing the concentration of glucose which could be due to the pronounced antihyperglycemic activity of nano-DDA over free DDA.

Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound) loaded polycaprolactone (nano-DDA) was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS) studies. Fourier Transform InfraRed Spectroscopy (FTIR) was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter), zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis). Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs) revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

Preparation and in vitro evaluation of 5-fluorouracil-loaded PCL nanoparticles for colon cancer treatment

Nanoparticles loaded with 5-fluorouracil (5-FU) for colon cancer therapies were prepared using the solvent evaporation technique, which involved lyophilization by freeze-drying. Formulations produced a substantially high encapsulation efficiency of approximately 93%. A positive correlation was seen when increasing polycaprolactone (PCL) and/or PVA concentrations and the size of nanoparticles produced. Increasing PCL concentration had a considerable influence on PDI while increasing PVA concentration had a lesser effect. All nanoparticles possessed a negative zeta potential, particularly in formulations with low polymer and polymer emulsifier concentrations. The formulation with the lowest PCL and PVA concentration was characterized by the most optimal properties; which accounts for the desirable delayed release profile of the active drug in dissolution testing indicating an improved targeting capability and enhanced bioavailability at the action site. Cytotoxicity studies showed that 5-FU loaded PCL nanoparticles had higher antiproliferative effect than free 5-FU on Caco-2 cell line (p < 0.05). The encouraging results obtained offer reasons for optimism regarding the future of 5-FU nanoparticles as a promising drug delivery system which could be further improved by including either enteric coating or encapsulating the nanoparticles onto microparticles to overcome unanticipated degradation.

Development and Evaluation of Nateglinide Loaded Polycaprolactone Nanoparticles

Development and Evaluation of Nateglinide Loaded Polycaprolactone Nanoparticles

Fabrication and Tailoring of Eugenol Loaded Polycaprolactone Nanoparticles Using Response Surface Methodology

Fabrication and Tailoring of Eugenol Loaded Polycaprolactone Nanoparticles Using Response Surface Methodology

Anandamide-loaded nanoparticles: Preparation and characterization

Objective: Preparation and characterization of anandamide (N-arachidonoyl-ethanolamine, AEA) loaded polycaprolactone nanoparticles (PCL NP) as a research tool to clarify the presence of an AEA transporter in cell membranes and to avoid AEA plastic adsorption and instability.Materials and methods: High performance liquid chromatography and light scattering were used to determine encapsulation efficiency, particle size, drug release, permeability and stability.Results: A high encapsulation efficiency 96.05 ± 1.77% and a particle size of 83.52 ± 21.38 nm were obtained. Nearly 40% of AEA remained in the NP after a 99.9% dilution and only 50% was released after 24 h at 37°C with a 99% dilution. PCL NP prevented the adsorption of the drug to polypropylene or polystyrene, but not to acrylic multiwell plates. Drug permeability through artificial membranes was low (10−7 to 10−8 cm/s) and was affected by the presence of NP. NP increased AEA stability in suspension (drug half-life 431 h vs. 12 h) and freeze-dried with 5% sucrose.Conclusion: This article presents the first study where stable AEA-loaded NP with high encapsulation efficiencies have been obtained.