Chitosan-coated PLGA Nanoparticles Research Articles

Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells.

Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. The developed IVO-PLGA-NPs were evaluated for their particle size (171.7±4.9 nm), PDI (0.333), ZP (-23.0±5.8 mV), EE (96.3±4.3%), and DL (9.66±1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3±5.2 nm), PDI (0.311), ZP +25.9±5.7 mV, EE (90.8±5.7%), and DL (9.42±0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.

Mucoadhesive Chitosan-Coated PLGA Nanoparticles of Ashwagandha Extract for Colon-Targeted Delivery

Mucoadhesive Chitosan-Coated PLGA Nanoparticles of Ashwagandha Extract for Colon-Targeted Delivery

Advance nanotherapeutic approach for systemic co-delivery of mitoxantrone loaded chitosan coated PLGA nanoparticles to improve the chemotherapy against human non-small cell lung cancer

Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) are a type of polymeric nanoparticles that offer benefits over metallic NPs, such as the capacity to sustain therapeutic drug levels for extended periods. In the current study, in order to enhance the solubility, stability, and anti-cancer effect of the mitoxantrone drug (Mtx), mitoxantrone-loaded chitosan-coated PLGA NPs (Mtx-loaded Cht-PLGA NPs) were synthesized. Mtx-loaded Cht-PLGA NPs were coated with Cht to improve mucoadhesiveness and colloidal stability. The synthesized NPs were checked for their size, morphology, zeta potential, encapsulation efficiency, FTIR and in vitro release studies. The anti-cancer potential of Mtx-loaded Cht-PLGA NPs were assessed in the A-549 lung cancer cell lines. Additionally, compared to pure Mtx, the viability of A-549 cells markedly decline with increasing concentrations of Mtx-loaded Cht-PLGA NPs. The cellular uptake study also confirms that chitosan coating greatly enhanced the uptake of the nanoparticles. Further, the ability to stimulate the reactive oxygen species (ROS) generation at the IC50 concentration of Mtx-loaded Cht-PLGA NPs was confirmed by using carboxy-2,7-dichloro-dihydro-fluorescein diacetate. Further, the western blotting revealed the down-regulation of TGF-β, vimentin, and upregulation of p53. This study reveals that the developed mitoxantrone-loaded cationically charged polymeric nano vehicle would be effectively less cytotoxic and have improved efficacy against lung cancer.

Surface modified biodegradable nanoparticles of Gabapentin. An approach to increase cell uptake

Improving delivery to the regions of Central Nervous System has been a long-explored quest for scientists. Delivery through nanocarriers provide potential solution but it is also important to choose material which is biodegradable in nature. Further once administered inside body these nanocarriers get cleared from the system very fast leading to poor bioavailability. It is important to modify surfaces of nanoparticles with materials which can improve the residence time as well as cellular uptake of drugs at the site of action. In the present study poly (lactic-co-glycolic acid) (PLGA) was used as a biodegradable polymer wherein the surface of the nanoparticles was modified with a cationic polymer, chitosan. Chitosan has been widely used in drug delivery via nasal route as it imparts mucoadhesive property to the nanoparticle there by increasing its mean residence time. Gabapentin was encapsulated in PLGA nanoparticles as it belongs to BCS class III, with low solubility and low permeability thus make it a suitable choice for delivering via surface modified nanoparticles so as to increase bioavailability. Chitosan coated PLGA nanoparticle loaded with gabapentin were prepared by nanoprecipitation method. Surface modified nanoparticles were optimized and developed to obtain smaller particle size (180.7 nm), zetapotential (36.7 mV) and maximum entrapment efficiency (75.6%). Optimized chitosan coated PLGA nanoparticle was further evaluated for its surface morphology by FTIR & DSC. Spherical nature of the nanoparticles was evaluated by SEM & TEM. Biphasic release pattern was observed for surface modified nanoparticles with sustained release up to 72 h. Optimized formulation was evaluated for % cell viability in comparison with uncoated nanoparticles and drug solution alone via MTT assay on Neuro-2a cells. Nanoparticle localization in neuro-2a cells was assessed by Confocal Laser Microscopy when treated with Rhodamine123 labelled Chitosan coated PLGA nanoparticles. These findings suggest a significant enhanced uptake of surface modified PLGA nanoparticles was observed as compared to uncoated nanoparticles.

Chitosan-coated PLGA nanoparticles for transcutaneous immunization: Skin distribution in lysozyme-sensitized mice

The effect of transcutaneous immunization was studied using a combined system of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and iontophoresis (IP). Both hen egg-white lysozyme (HEL)-loaded PLGA nanoparticles coated with chitosan hydroxypropyltrimonium chloride and their fluorescent nanoparticles were prepared using an antisolvent diffusion method. Their mean volume diameters were 87.6 ± 38.9 nm and 84.9 ± 27.6 nm, respectively. It was suggested from the results of the ex vivo skin accumulation study using fluorescent nanoparticles that the HEL released from the nanoparticles to the skin surface was efficiently delivered to antigen-presenting cells. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study using lysozyme-sensitized mice. As results, the group using nanoparticles and IP showed 1.33 times higher HEL-specific IgG1 titer than a sham treatment group. The HEL-specific IgG2a titer was 1.36 times higher in the nanoparticles and IP group than in the HEL solution and IP group. It was suggested from the quantification results of total IgE in serum that the combined use of PLGA nanoparticles and IP reduced the total IgE concentration. The level of cytokines may have decreased due to Th1 cell activation and relative suppression of Th2 cells. The cytokine level is presumed to be reduced by activation of Th1 cells and relative suppression of Th2 cells. The histamine amount in plasma and rectal temperature after the induction of anaphylactic shock using lysozyme-sensitized mice were also studied, which indicates that the combined use of PLGA nanoparticles and IP may provide the same therapeutic effect as an injection.

Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery of Peganum harmala smoke extract to breast cancer cells

In this study, PLGA-NPs coated with folic acid-chitosan (PCF-NPs) loaded with Peganum harmala smoke extract (PSE) were synthesized (PSE-PCF-NPs), and their anti-cancer effects were evaluated. PSE-PCF-NPs were synthesized by the nanoprecipitation method and then characterized by DLS, SEM, and FTIR methods. HPLC and UV–vis spectroscopy were used to evaluate the PSE’s folic acid (FA) binding and encapsulation. PSE-PCF-NPs-mediated cell viability and apoptosis were investigated by MTT, qPCR, flow cytometry, AO/PI, and DAPI staining. Anti-oxidant properties of PSE-PCF-NPs were evaluated by ABTS, DPPH, FRAP, and ROS. Angiogenic effects of PSE-PCF-NPs were assessed by CAM assay. The PSE-PCF-NPs (276.16 nm, PDI: 0.25, zeta-potential: +32.31 mV, FB: 67.6% and %EE: 89%) demonstrated selective toxicity on MCF-7 cells (IC50: 75.65 μg ml−1). The occurrence of apoptosis in MCF-7 cells was confirmed by up-regulation of P53, Cas-3, and Cas-9 genes, increased SubG1 phase cells, and the results of fluorescent staining. Scavenging free radicals, reducing iron ions, increasing intracellular ROS, and decreasing SOD gene confirmed the anti- and pro-oxidant effects of PSE-PCF-NPs outside and inside MCF-7 cells. Reduction of angiogenic factors in CAM assay showed the anti-angiogenic effects of PSE-PCF-NPs. PSE-PCF-NPs, due to their anti-cancer properties, can be considered a therapeutic agent in cancer studies.

Brain targeted delivery of carmustine using chitosan coated nanoparticles via nasal route for glioblastoma treatment

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 μg ml−1) as compared to drug suspension (90.02 μg ml−1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme.

Paclitaxel and Lapatinib dual loaded chitosan-coated PLGA nanoparticles enhance cytotoxicity by circumventing MDR1-mediated trastuzumab resistance in HER2 positive breast cancers: In-vitro and in-vivo studies

Treatment options for multidrug-resistant breast cancer are limited and ineffective. Few combinations of chemotherapeutic agents are clinically successful in treating multiple drug-resistant cancers. However, due to their varied pharmacokinetic characteristics, it is challenging to deliver dual drugs to the tumor simultaneously with the best proportion by simple co-administration. This study aimed to generate chitosan-coated PLGA nanoparticles delivering a synergistic combination of Paclitaxel (PTX) and Lapatinib (LPB) to improve efficacy in patients with multidrug-resistant breast cancer. In comparison to sensitive BT-474 cells, the 3:1 M ratio of PTX/LPB demonstrated significant synergism with a reversal index of approximately 13.4 in trastuzumab-resistant BT-474/TR cells. Particle diameters of the prepared chitosan (CS) PLGA Nps ranged from 157.4 ± 9.2 to 263.5 ± 13.5 nm. CS-coated Nps exhibited good EE and DL values of 80.8 ± 3.4% and 1.5 ± 0.12%, respectively. Moreover, CS-coating allowed successful co-delivery of PTX and LPB, resulting in the maximum in-vitro release within 72 h. Cytotoxicity against BT-474/TR cells was significantly increased when CS-coated dual loaded Nps were compared to other Nps, including free PTX, LPB, and their mixture. Quantification of the intracellular drug accumulation revealed that the encapsulation effectively increased drug uptake in BT-474/TR cells. These CS-coated dual loaded Nps exerted an excellent synergistic effect in BT-474/TR cells, leading to significantly improved cell inhibition via circumventing the MDR1 mediated trastuzumab resistance. Additionally, co-delivery of PTX and LPB demonstrated the most effective tumor growth reduction in the BT-474/TR human breast tumor xenograft compared to the saline control, single loaded PTX, and LPB Nps and a mixture of PTX and LPB combinations. The data suggest that CS-coated PLGA Nps loaded with PTX and LPB concurrently may be one of the most promising formulations for treating MDR1 mediated chemoresistance in HER2-positive breast tumors.

Chitosan-Coated PLGA Nanoparticles Encapsulating Triamcinolone Acetonide as a Potential Candidate for Sustained Ocular Drug Delivery.

The current treatment for the acquired retinal vasculopathies involves lifelong repeated intravitreal injections of either anti-vascular endothelial growth factor (VEGF) therapy or modulation of inflammation with steroids. Consequently, any treatment modification that decreases this treatment burden for patients and doctors alike would be a welcome intervention. To that end, this research aims to develop a topically applied nanoparticulate system encapsulating a corticosteroid for extended drug release. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) supports the controlled release of the encapsulated drug, while surface modification of these NPs with chitosan might prolong the mucoadhesion ability leading to improved bioavailability of the drug. Triamcinolone acetonide (TA)-loaded chitosan-coated PLGA NPs were fabricated using the oil-in-water emulsion technique. The optimized surface-modified NPs obtained using Box-Behnken response surface statistical design were reproducible with a particle diameter of 334 ± 67.95 to 386 ± 15.14 nm and PDI between 0.09 and 0.15. These NPs encapsulated 55–57% of TA and displayed a controlled release of the drug reaching a plateau in 27 h. Fourier-transform infrared spectroscopic (FTIR) analysis demonstrated characteristic peaks for chitosan (C-H, CONH2 and C-O at 2935, 1631 and 1087 cm−1, respectively) in chitosan-coated PLGA NPs. This result data, coupled with positive zeta potential values (ranged between +26 and +33 mV), suggests the successful coating of chitosan onto PLGA NPs. Upon coating of the NPs, the thermal stability of the drug, polymer, surfactant and PLGA NPs have been enhanced. The characteristics of the surface-modified NPs supports their use as potential candidates for topical ocular drug delivery for acquired retinal vasculopathies.

Chitosan-Coated PLGA Nanoparticles Loaded with Peganum harmala Alkaloids with Promising Antibacterial and Wound Healing Activities.

Wound healing is a major healthcare concern, and complicated wounds may lead to severe outcomes such as septicemia and amputations. To date, management choices are limited, which warrants the search for new potent wound healing agents. Natural products loaded in poly (lactic-co-glycolic acid) (PLGA) coated with chitosan (CS) constitute a promising antibacterial wound healing formulation. In this work, harmala alkaloid-rich fraction (HARF) loaded into PLGA nanoparticles coated with chitosan (H/CS/PLGA NPs) were designed using the emulsion-solvent evaporation method. Optimization of the formulation variables (HARF: PLGA and CS: PLGA weight ratios, sonication time) was performed using the 33 Box–Behnken design (BBD). The optimal NPs were characterized using transmission electron microscopy (TEM) and Attenuated Total Reflection Fourier-Transformed Infrared Spectroscopy (ATR-FTIR). The prepared NPs had an average particle size of 202.27 ± 2.44 nm, a PDI of 0.23 ± 0.01, a zeta potential of 9.22 ± 0.94 mV, and an entrapment efficiency of 86.77 ± 4.18%. In vitro drug release experiments showed a biphasic pattern where an initial burst of 82.50 ± 0.20% took place in the first 2 h, which increased to 87.50 ± 0.50% over 72 h. The designed optimal H/CS/PLGA NPs exerted high antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.125 and 0.06 mg/mL, respectively) compared to unloaded HARF (MIC of 0.50 mg/mL). The prepared nanoparticles were found to be biocompatible when tested on human skin fibroblasts. Moreover, the wound closure percentage after 24 h of applying H/CS/PLGA NPs was found to be 94.4 ± 8.0%, compared to free HARF and blank NPs (68.20 ± 5.10 and 50.50 ± 9.40%, respectively). In conclusion, the three components of the developed nanoformulation (PLGA, chitosan, and HARF) have synergistic antibacterial and wound healing properties for the management of infected wounds.

Gefitinib loaded PLGA and chitosan coated PLGA nanoparticles with magnified cytotoxicity against A549 lung cancer cell lines.

In the current study, gefitinib loaded PLGA nanoparticles (GFT-PLGA-NPs) and chitosan coated PLGA nanoparticles (GFT-CS-PLGA-NPs) were synthesized to investigate the role of surface charge of NPs for developing drug delivery system for non-small-cell lung cancer (NSCLC). The developed NPs were evaluated for their size, PDI, zeta potential (ZP), drug entrapment, drug loading, DSC, FTIR, XRD, in vitro release profile, and morphology. The anti-cancer activity of GFT loaded PLGA NPs and GFT loaded CS-PLGA-NPs were examined in human A549 lung cancer cell lines. In vitro release studies of GFT-CS-PLGA-NPs showed more sustained release in comparison to GFT-PLGA-NPs due surface charge attraction of chitosan. In addition, viability of A549 cells decreases significantly with the increasing concentration of GFT-PLGA NPs and GFT-CS-PLGA-NPs when compared to that of pure GFT and blank PLGA NPs. In addition, the microscopic analysis and counting of viable cells also validate the cytotoxicity of the developed NPs. This investigation proved that the developed NPs would be efficient carriers to deliver GFT with improved efficacy against NSCLC.

Novel Silibinin Loaded Chitosan-Coated PLGA/PCL Nanoparticles Based Inhalation Formulations with Improved Cytotoxicity and Bioavailability for Lung Cancer

Silibinin is widely used as an anticancer agent. There are important matters of concern regarding the drug pharmacokinetics related to the conventional formulation due to their low solubility and bioavailability. The aim of the present investigation was to develop, characterize, and evaluate chitosan-coated PLGA/PCL nanoparticles containing Silibinin (SB) intended for pulmonary delivery for treating lung cancer. Nanoparticles were prepared by double emulsion solvent evaporation method followed by lyophilized to obtain inhalation powder form. The prepared nanoparticles (NPs) were evaluated for their physicochemical characteristic along with DSC, FTIR, and SEM. The anticancer activity of SB-loaded NPs was assessed in the human A549 lung cancer cell line utilizing MTT assay and anti-cancer potential assessed by clonogenic assay. The pharmacokinetics and tissue distribution studies of SB-loaded NPs were assessed in comparison with the SB solution. The prepared NPs exhibited particle sizes in the range of 187–284 nm. Zeta potential was altered from negative to positive due to the coating with chitosan. Chitosan-coated NPs showed the sustain release effect up to 48 h with an aerodynamic particle size of 1.82 μm. Moreover, a tremendous increase in cell inhibition was determined by chitosan-coated PLGA NPs. Pharmacokinetics study showed that chitosan coating onto PLGA nanoparticles promoted to release drug in the lungs and increased vivo residence time. Thus, proposed formulations with improved bioavailability can be useful for efficient pulmonary delivery. These nanoparticles coated with chitosan could open a new avenue for effective treatment of lung cancer.

Chitosan-coated PLGA nanoparticles for the nasal delivery of ropinirole hydrochloride: In vitro and ex vivo evaluation of efficacy and safety.

Nose-to-brain delivery is an attractive route for direct drug delivery to the central nervous system (CNS), avoiding hepatic first-pass metabolism and solving blood-brain barrier passage issues. Therefore, the aim of the present study was the development of PLGA and PLGA/chitosan (chit) nanoparticles (NPs) with mucoadhesive properties, able to encapsulate ropinirole hydrochloride (RH), an anti-Parkinsonian dopaminergic agonist, and suitable to promote RH delivery across the nasal mucosa. NPs produced by nanoprecipitation showed spherical shape and a mean average size of 98.8 nm and 468.0 nm (PLGA and PLGA/chit, respectively). RH loaded PLGA/chit NPs showed a complete release of the drug in simulated nasal electrolyte solution (SNES) over the period of 24 h and increased the permeation of RH through sheep nasal mucosa by 3.22-fold in comparison to PLGA NPs. None of RH loaded NPs induced hemolysis in whole blood or the production of reactive oxygen species (ROS) in Raw 264.7 cells. On their turn, PLGA/chit NPs decreased cell viability of Raw 264.7 cells and Peripheral Blood Mononuclear Cells (PBMCs) in a concentration-dependent manner. These results revealed that, particularly PLGA/chit NPs, could be a valuable carrier for the delivery of RH to the CNS, opening a new path for Parkinson's disease therapy.

Preparation and Characterization of Chitosan Coated PLGA Nanoparticles of Resveratrol: Improved Stability, Antioxidant and Apoptotic Activities in H1299 Lung Cancer Cells

Resveratrol (RES) is a polyphenolic compound which has shown beneficial pharmacological effects such as anti-inflammatory, antioxidant, and anti-cancer effects. However, poor aqueous solubility, bioavailability, and low stability are the major limitations to the clinical application of RES. Therefore, in the present study, chitosan (CS) coated PLGA nanoparticles of RES (CS-RES-PLGA NPs) was developed, characterized and its anticancer activity was evaluated in the H1299 lung carcinoma cell line. The effects of the increase in CS coating and cryoprotectant concentration on particle size, polydispersity index (PDI) and zeta potential (ZP) were determined. The particle size, PDI, ZP and entrapment efficiency of the optimized CS-RES-PLGA NPs were found to be 341.56 ± 7.90 nm, 0.117 ± 0.01, 26.88 ± 2.69 mV and 75.13% ± 1.02% respectively. The average particle size and ZP showed a steady increase with an increase in CS concentration. The increase in positive zeta potential is evident for higher CS concentrations. The effect of trehalose as cryoprotectant on average particle size was decreased significantly (p &lt; 0.05) when it was increased from 1%−5% w/v. TEM and SEM showed uniform particle distribution with a smooth surface and spherical shape. The CS coating provides modulation of in vitro drug release and showed a sustained release pattern. The stability of RES loaded PLGA NPs was improved by CS coating. CS-coated NPs showed greater cytotoxicity and apoptotic activities compared to free RES. The CS coated NPs had a higher antioxidant effect than the free RES. Therefore, CS coated PLGA NPs could be a potential nanocarrier of RES to improve drug solubility, entrapment, sustain release, stability and therapeutic application.

Improvement of Ocular Efficacy of Levofloxacin by Bioadhesive Chitosan Coated PLGA Nanoparticles: Box-behnken Design, In-vitro Characterization, Antibacterial Evaluation and Scintigraphy Study.

Conjunctivitis is considered as a common infection of ocular surfaces. Eye drop is most commonly used for treatment of conjunctivitis, but has some drawback like 95% drug eliminated after administration. Administration of levofloxacin to the anterior site in form of chitosan coated poly (lactic-co-glycolic acid) nanoparticles (LFV-CS-PLGA-NPs) expected to overcome these problem and increasing corneal contact time and permeability for effective treatment of bacterial conjunctivitis. The Nanoparticles were developed by single emulsion solvent evaporation technique and optimized for different variables (chitosan, poly (lactide-co-glycolic acid) and polyvinyl alcohol concentration) by employing three factors, three levels Box–Behnken statistical design. The nanoparticles were evaluated for particle size, drug loading, entrapment efficiency, drug release, ex-vivo permeation, ocular tolerance, antimicrobial study, confocal laser microscopy, and Gamma scintigraphy study. The particle size and PdI of the optimized nanoparticles were 169.968 ± 15.23 nm and 0.13 ± 0.03, respectively, where as entrapment efficiency and drug loading is 49.54 ± 2.43% and 11.29 ± 2.13% with extended release profile and strong mucoadhesion. DSC data indicated levofloxacin formed molecular dispersion within coated nanoparticles. Corneal flux showed significantly (P < 0.05) higher permeation as compared to marketed formulation. Formulation was nonirritant and possessed good antibacterial activity. Gamma Scintigraphy showed slow drainage compared to drug solution, indicating reduction in nasolachrymal drainage. The Gamma Scintigraphy study indicated the CS coated PLGA-NPs have high corneal residence time as compared to drug solution. So, it is revealed that LFV-CS-PLGA-NPs increase the drug concentration over ocular tissue and potential usefulness for sustained drug delivery.

Strategic Design of Dicer Substrate siRNA to Mitigate the Resistance Mediated by ABCC1 in Doxorubicin-resistant Breast Cancer

The current study involved designing of a small interfering ribonucleic acid-loaded folate functionalized chitosan-coated PLGA nanoparticles to evaluate tumor targeting potential in drug-resistant breast cancer cells. The synthesized conjugate was utilized to develop small interfering ribonucleic acid encapsulated nanoparticles. The developed siRNA nanoparticles were with a particle size of ˂250 nm and could offer protection against serum nucleases. A significant uptake of the folic acid conjugated formulation was noticed, affirming that the nanoparticles selectively targeted the drug-resistant cancer cells. Through the polymerase chain reaction and Western blot, it was evident that ABCC1 expression was significantly reduced (˂95%). The efficiency of small interfering ribonucleic acid with doxorubicin could be evaluated by cytotoxicity assay and it was found that the ABCC1 targeted small interfering ribonucleic acid minimized the resistance of doxorubicin-resistant MCF- 7 cell line to doxorubicin. The main objective in developing this folate conjugated nanoformulation was to enhance the targetability to the cancer cells and to increase the sensitivity of drug-resistant tumors to doxorubicin

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Itraconazole (ITR) is a broad-spectrum antifungal drug, which has been shown to possess some promising anticancer, anti-proliferative, and anti-angiogenic properties in some cancers, such as cancers of the lung, breast, and skin. However, ITR has some drawbacks, such as poor water solubility, which hinder its use as a therapeutic agent. Therefore, in the present study, we developed and characterized chitosan-coated PLGA nanoparticles of itraconazole and studied their anticancer activities in H1299 lung cancer cells. The prepared ITR nanoparticles showed a small particle size, narrow poly dispersity index (PDI), positive zeta potential, and a controlled drug release profile. The cytotoxicity of ITR nanoparticles (NPs) on H1299 cancer cells after 24 h of exposure was greater than that of the ITR solution. Apoptosis of cancer cells exposed to ITR nanoparticles was also enhanced in comparison with the ITR solution. At the molecular level, ITR NPs were more effective than ITR solution in inducing pro-apoptotic Bax and p53 while reducing anti-apoptotic Bcl2 protein expression. ITR NPs were more effective than ITR solution in arresting cells both at the G0/G1 as well as G2/M phases of the cell cycle. Hence, repurposing itraconazole by encapsulation into PLGA NPs with chitosan coating is a potentially promising approach to treat lung cancers.

&lt;p&gt;In vitro–in vivo evaluation of chitosan-PLGA nanoparticles for potentiated gastric retention and anti-ulcer activity of diosmin&lt;/p&gt;

BackgroundDiosmin showed poor water solubility and low bioavailability. Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were successfully used to improve the drugs solubility and bioavailability. Coating of PLGA nanoparticles with chitosan can ameliorate their gastric retention and cellular uptake.MethodologyPLGA nanoparticles of diosmin were prepared using different drug and polymer amounts. Nanoparticles were selected based on entrapment efficiency% (EE%) and particle size measurements to be coated with chitosan. The selected nanoparticles either uncoated or coated were evaluated regarding morphology, ζ-potential, solid-state characterization, in vitro release, storage stability, and mucoadhesion. The anti-ulcer activity (AA) against ethanol-induced ulcer in rats was assessed through macroscopical evaluation, histopathological examination, immunohistochemical localization of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transmission electron microscopic examination of gastric tissues compared to free diosmin (100 mg/kg) and positive control.ResultsBased on EE% and particle size measurements, the selected nanoparticles, either uncoated or coated with 0.1% w/v chitosan, were based on 1:15 drug-PLGA weight ratio and 20 mg diosmin employing methylene chloride as an organic phase. Examination by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed nanoscopic spherical particles. Drug encapsulation within the selected nanoparticles was suggested by Fourier transform-infrared, differential scanning calorimetry (DSC) and X-ray diffractometry results. Chitosan-coated nanoparticles were more stable against size enlargement probably due to the higher ζ-potential. Only coated nanoparticles showed gastric retention as revealed by SEM examination of stomach and duodenum. The superior AA of coated nanoparticles was confirmed by significant reduction in average mucosal damage, the majority of histopathological changes and NF-κB expression in gastric tissue when compared to positive control, diosmin and uncoated nanoparticles as well as insignificant difference relative to normal control. Coated nanoparticles preserved the normal ultrastructure of the gastric mucosa as revealed by TEM examination.ConclusionThe optimized chitosan-coated PLGA nanoparticles can be represented as a potential oral drug delivery system of diosmin.

Antitumor efficacy of Folic Acid conjugated Polymeric Nanoparticles of SN-38 after oral delivery

The objective of the present research was to develop folic acid conjugated polymeric nanoparticles (FCsPNP) and to investigate its therapeutic effectiveness in xenograft Colon tumor models after oral delivery. Chitosan coated PLGA nanoparticles (CsPNP) were prepared by polyelectrolyte complexation method and it was further conjugated with Folic acid. Optimized formulation was investigated for particle size, zeta potential, polydispersity index (PdI), % entrapment drug loading and in vitro release. The morphology was observed by SEM and TEM images. Tumor regression studies were conducted on Balb/c mice implanted with Colo-26 cells. FCsPNP were successfully prepared and optimized. In vitro parameters viz. Particle size, Zeta potential, PdI were found to be optimum. The in vitro % release is directly correlated with the nature of polymers and folate conjugation. In vivo tumor regression studies found the formulations to be less toxic than Irinotecan hydrochloride (IHCl). CsPNP and FCsPNP were successfully prepared and evaluated for antitumor efficacy after oral delivery. FCsPNP were more effective in the colon tumor treatment and found to be less toxic than IHCl thus making it a potential drug delivery candidate for future anticancer therapy.&#x0D; Keywords: Nanoparticles, Xenograft colon tumor, Chitosan, Irinotecan hydrochloride

Surface engineering of resveratrol to improve neuro-protection and functional recovery after spinal cord injury in rat

To modify surface of resveratrol using nanotechnology that may ensure optimum drug availability at the spinal cord injury site and reduce its dosing frequency. Chitosan coated PLGA nanoparticles were prepared by double emulsion solvent evaporation method and characterized as spherical shape, tiny particles, smooth surface with 172.3 ± 20.8 nm size and +32.2 mV zeta potential. Nanoparticles did not show cytotoxicity at effective dose. Release rate of Res from NP was slow and controlled. Particles reduced the level of inflammatory cytokines (Il-1β and TNF-α) and increased level of anti-inflammatory cytokine (IL-10) significantly. Particles restored improved functional outcome of the animals and histopathological alterations (larger pseudocyst toward normal) and helped reduce the decrease in SCI driven apoptosis of the neurons as revealed by TUNEL and Bax florescent analysis. In conclusion, chitosan coated PLGA nanoparticles of Resveratrol we observed with prominent utility in treating post SCI like conditions by reducing secondary inflammation associated with SCI, protecting neurons from apoptosis and restoring normal behaviour of the animals. Results show clinical pertinency of particles in the treatment of post SCI.