Carboxymethyl chitosan nanoparticles coupled with CD59-specific ligand peptide for targeted delivery of C-phycocyanin to HeLa cells

The combination of nanotechnology and medicine will be the next generation of vehicles for targeted drug delivery. Carboxymethyl chitosan loaded with the anticancer drug C-phycocyanin and the CD59-specific ligand peptide for cancer cell targeting were used to create C-phycocyanin/carboxymethyl chitosan–CD59-specific ligand peptide nanoparticles using the ionic-gelation method. Optimal synthesis conditions, selected by response surface methodology, comprised the ratio carboxymethyl chitosan:C-phycocyanin = 3:1, and carboxymethyl chitosan and CaCl2 concentrations of 2.0 and 1.0 mg/mL, respectively. The resulting nanoparticles were spherical, with diameters of approximately 200 nm; the entrapment efficient was about 65%; and the drug loading was about 20%. The release of C-phycocyanin from C-phycocyanin/carboxymethyl chitosan nanoparticles was pH sensitive and had a sustainable effect in vitro. Guided by the CD59-specific ligand peptide, the nanoparticles efficiently targeted the surface of HeLa cells and had an obvious inhibitory effect on HeLa cell proliferation as determined by methyl thiazolyl tetrazolium assays. The nanoparticles were hemocompatible and induced apoptosis by upregulation of cleaved caspase-3 and cleaved polyADP-ribose polymerase proteins, and downregulation of Bcl-2 proteins. Our study provides a novel approach to the research and development of marine drugs, and support for targeted therapy using anticancer drugs.

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In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-010-3998-4 ◽

2010 ◽

Vol 21 (5) ◽

pp. 1587-1597 ◽

Cited By ~ 76

Author(s):

Sumanta K. Sahu ◽

Sanjay K. Mallick ◽

Susmita Santra ◽

Tapas K. Maiti ◽

Sudip K. Ghosh ◽

...

Keyword(s):

Folic Acid ◽

Targeted Delivery ◽

Chitosan Nanoparticles ◽

Carboxymethyl Chitosan ◽

In Vitro Evaluation

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Synthesis, Characterization, and Evaluation of Nanoparticles Loading Adriamycin Based on 2-Hydroxypropyltrimethyl Ammonium Chloride Chitosan Grafting Folic Acid

Polymers ◽

10.3390/polym13142229 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2229

Author(s):

Yingqi Mi ◽

Jingjing Zhang ◽

Lulin Zhang ◽

Qing Li ◽

Yuanzheng Cheng ◽

...

Keyword(s):

Folic Acid ◽

Cancer Cells ◽

Ammonium Chloride ◽

Drug Loading ◽

Chitosan Nanoparticles ◽

Radical Scavenging ◽

Inhibitory Effect ◽

Hydrodynamic Diameter ◽

The Novel

Chitosan nanoparticles have been considered as potential candidates for drug loading/release in drug delivery systems. In this paper, nanoparticles (HACAFNP) loading adriamycin based on 2-hydroxypropyltrimethyl ammonium chloride chitosan grafting folic acid (HACF) were synthesized. The surface morphology of the novel nanoparticles was spherical or oval, and the nanoparticles exhibited a relatively small hydrodynamic diameter (85.6 ± 2.04 nm) and positive zeta potential (+21.06 ± 0.96 mV). The drug release of nanoparticles was assayed and represented a burst effect followed by a long-term steady release. Afterward, the antioxidant efficiencies of nanoparticles were assayed. In particular, the target nanoparticles exhibited significant enhancement in radical scavenging activities. Cytotoxicities against cancer cells (MCF-7, BGC-823, and HEPG-2) were estimated in vitro, and results showed nanoparticles inhibited the growth of cancer cells. It’s worth noting that the inhibition index of HACAFNP against BGC-823 cells was 71.19% with the sample concentration of 25 μg/mL, which was much higher than the inhibitory effect of ADM. It was demonstrated that the novel nanoparticles with dramatically enhanced biological activity, reduced cytotoxicity, and steady release could be used as the practical candidates for drug loading/release in a delivery system.

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Apoptotic effect of novel pyrazolone-based derivative [Cu(PMPP-SAL)(EtOH)] on HeLa cells and its mechanism

Scientific Reports ◽

10.1038/s41598-020-75173-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Delizhaer Reheman ◽

Jing Zhao ◽

Shan Guan ◽

Guan-Cheng Xu ◽

Yi-Jie Li ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Hela Cells ◽

Copper Complexes ◽

Antibacterial Properties ◽

Inhibitory Effect ◽

Parp Cleavage ◽

Potential Candidate ◽

Tnf Α

Abstract Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC50 value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.

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Redox-Sensitive Ultrashort Peptide Hydrogel with Tunable Mechanical Properties for Anti-Tumor Drug Delivery

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2020.2974 ◽

2020 ◽

Vol 16 (11) ◽

pp. 1588-1599

Author(s):

Yiping Li ◽

Ying Zhu ◽

Shiyao Luo ◽

Yue He ◽

Zhewei Huang ◽

...

Keyword(s):

Mechanical Properties ◽

Targeted Delivery ◽

Subcutaneous Tissue ◽

Drug Loading ◽

Gelation Time ◽

In Vivo Studies ◽

Dependent Manner ◽

The Cross ◽

Hydrogel System

In this study, we report a new ultrashort peptide (LOC), which forms a redox-sensitive hydrogel after cross-linking with the mild oxidant H2 O2 and used it for tumor-targeted delivery of doxorubicin hydrochloride (DOX). LOC gelled within a few minutes in low-concentration H2 O2 solution. The concentration of H2 O2 significantly altered the gelation time and mechanical properties of the hydrogel. The in vitro micromorphology, secondary structure and rheology characterization of cross-linked hydrogels confirmed the sensitivity and injectability to reducing agent. The cross-linked hydrogel had a strong drug loading capacity, and the drug was released in a GSH concentration-dependent manner, following the Fick diffusion model. In addition, the cross-linked hydrogel showed no cytotoxicity to normal fibroblasts, and no damage to the subcutaneous tissue of mice was observed. In vitro cytotoxicity experiments showed that the DOX-hydrogel system exhibited good anti-cancer efficacy. In vivo studies using 4T1 tumor-bearing mice showed that the DOX-hydrogel system had a significant inhibitory effect on tumors. Therefore, the newly designed redox-sensitive hydrogel can effectively enhance the therapeutic efficacy of DOX and reduce toxicity, making it an attractive biological material.

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PREPARATION AND CHARACTERIZATION OF GLYCYRRHETINIC ACID-MODIFIED POLOXAMER 188/CHITOSAN NANOPARTICLES

NANO ◽

10.1142/s1793292013500422 ◽

2013 ◽

Vol 08 (04) ◽

pp. 1350042 ◽

Cited By ~ 1

Author(s):

JING WANG ◽

LI GUO ◽

LI FANG MA

Keyword(s):

High Performance ◽

Drug Loading ◽

Chitosan Nanoparticles ◽

Spherical Shape ◽

Glycyrrhetinic Acid ◽

Poloxamer 188 ◽

H Nmr ◽

Ft Ir

In this paper, we firstly synthesized glycyrrhetinic acid-modified double amino-terminated poloxamer 188 (GA–NH–POLO–NH–GA). The structure of the synthesized compound was confirmed by 1H-NMR and Fourier transform infrared (FT-IR) spectroscopy. Then the nanoparticles composed of GA–NH–POLO–NH–GA/chitosan (GA–NH–POLO–NH–GA/CTS) were prepared by an ionic gelation process. The characterization of the nanoparticles was measured by dynamic light scattering (DLS) and scanning electron microscope (SEM). The results showed that the nanoparticles were well dispersed with a spherical shape and the particle size was distributed between 100 nm and 300 nm. The cytotoxicity based on MTT assay against cells (QGY-7703 cells and L929 cells) showed that the nanoparticles had low toxicity and good biocompatibility. The encapsulation efficiency and drug loading of 5-fluorouracil-loaded nanoparticles (5-FU nanoparticles) were measured by high-performance liquid chromatography (HPLC) and fluorescence spectroscopy, ultraviolet-visible (UV-vis) absorbance. The encapsulation of 5-Fu-loaded CTS nanoparticles was 12.8% and the drug loading was 2.9%, while the encapsulation of 5-Fu-loaded GA–NH–POLO–NH–GA/CTS nanoparticles was 20.9% and the drug loading was 3.36%. The release profile showed that the GA–NH–POLO–NH–GA/CTS nanoparticles were available for sustained release of 5-Fu. The GA–NH–POLO–NH–GA/CTS nanoparticles have a higher affinity to the QGY-7703 cells, so indicated that the GA–NH–POLO–NH–GA/CTS nanoparticles have the capacity of liver-targeting in vitro.

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Preparation and Evaluation of Collagen-Based Patches as Curcumin Carriers

Polymers ◽

10.3390/polym12102393 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2393

Author(s):

Zoi Terzopoulou ◽

Anna Michopoulou ◽

Artemis Palamidi ◽

Elena Koliakou ◽

Dimitrios Bikiaris

Keyword(s):

Topical Treatment ◽

Chitosan Nanoparticles ◽

In Vitro Release ◽

Human Keratinocytes ◽

Inhibitory Effect ◽

Psoriatic Skin ◽

Burst Release ◽

Swelling Ratio ◽

Natural Polyphenol

Patients with psoriasis are dissatisfied with the standard pharmacological treatments, whether systemic or topical, with many of them showing interest in complementary and alternative medicine. Curcumin (Cur), a natural polyphenol derived from turmeric, has recently gained attention for skin-related diseases because of its proven anti-inflammatory action. However, topical treatment with Cur would be inadequate because of its hydrophobicity, instability, and low bioavailability. In addition, hyperkeratosis and lack of moisture in psoriatic skin result in low penetration that would prevent actives from permeating the stratum corneum. In this work, a polymer-based formulation of Cur for the topical treatment of psoriasis is reported. To improve the physicochemical stability of Cur, it was first encapsulated in chitosan nanoparticles. The Cur-loaded nanoparticles were incorporated in a hydrophilic, biocompatible collagen-based patch. The nanoparticle-containing porous collagen patches were then chemically cross-linked. Morphology, chemical interactions, swelling ratio, enzymatic hydrolysis, and Cur release from the patches were evaluated. All patches showed excellent swelling ratio, up to ~1500%, and after cross-linking, the pore size decreased, and their hydrolysis rates decelerated. The in vitro release of Cur was sustained with an initial burst release, reaching 55% after 24 h. Cur within the scaffolds imparted a proliferation inhibitory effect on psoriatic human keratinocytes in vitro.

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In Vitro Cytotoxicity and Antitumor Activity of Dual-Targeting Drug Delivery System Based on Modified Magnetic Carbon by Folate

Journal of Nanomaterials ◽

10.1155/2020/7147130 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Jinglei Du ◽

Qiang Li ◽

Lin Chen ◽

Shicai Wang ◽

Li Zhang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Hela Cells ◽

Folate Receptor ◽

Drug Loading ◽

Magnetic Characteristics ◽

Loading Capacity ◽

Dual Targeting

A dual-targeting drug delivery system (DTDDS) with magnetic targeting and active targeting was obtained to improve the targeting and drug-loading capacity of magnetic drug nanocarriers. An ultraviolet-visible spectrophotometer and flow cytometry were used to investigate the drug-loading and release capacity, cytotoxicity, and inhibition of tumor cell proliferation, separately. Results show that DTDDS has obvious magnetic characteristics, on which the modification amount of folic acid is 64.82 mg g-1. Doxorubicin was taken as a template drug to evaluate its drug-loading capacity, which was as high as 577.12 mg g-1. Good biocompatibility and low cytotoxicity of DTDDS were further confirmed. Moreover, DTDDS can target the folate receptor on the surface of HeLa cells and deliver doxorubicin into HeLa cells, thereby increasing the proliferation inhibition for cancer cells. Therefore, this new dual-targeting drug delivery system shows potential in significantly reducing the toxic side effects of chemotherapy and improving chemotherapy efficiency.

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Targeted Dual Intervention-Oriented Drug-Encapsulated (DIODE) Nanoformulations for Improved Treatment of Pancreatic Cancer

Cancers ◽

10.3390/cancers12051189 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1189

Author(s):

Vijay Sagar Madamsetty ◽

Krishnendu Pal ◽

Shamit Kumar Dutta ◽

Enfeng Wang ◽

Debabrata Mukhopadhyay

Keyword(s):

Pancreatic Cancer ◽

Side Effects ◽

Anticancer Agents ◽

Targeted Delivery ◽

Drug Loading ◽

Ductal Adenocarcinoma ◽

Combination Therapies ◽

Term Survival ◽

Therapeutic Benefits

Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing therapeutic benefits by offering cocktail drug loading and minimizing chemotherapy-associated side effects. Nanoformulations-aided deliveries of anticancer agents have been a success in recent years. Yet, improving the tumor-targeted delivery of drugs to PDAC remains a major hurdle. In the present paper, we developed several new tumor-targeted dual intervention-oriented drug-encapsulated (DIODE) liposomes. We successfully formulated liposomes loaded with gemcitabine (G), paclitaxel (P), erlotinib (E), XL-184 (c-Met inhibitor, X), and their combinations (GP, GE, and GX) and evaluated their in vitro and in vivo efficacies. Our novel DIODE liposomal formulations improved median survival in comparison with gemcitabine-loaded liposomes or vehicle. Our findings are suggestive of the importance of the targeted delivery for combination therapies in improving pancreatic cancer treatment.

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Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502014000400022 ◽

2014 ◽

Vol 50 (4) ◽

pp. 869-876 ◽

Cited By ~ 7

Author(s):

Neha Gulati ◽

Upendra Nagaich ◽

Shubhini Saraf

Keyword(s):

Drug Release ◽

Polymeric Nanoparticles ◽

Release Kinetics ◽

Mode Of Delivery ◽

Chitosan Nanoparticles ◽

Entrapment Efficiency ◽

Tween 80 ◽

Fickian Diffusion ◽

Novel Approach

The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action.

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Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽

10.3390/pharmaceutics12111059 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1059

Author(s):

Saif Ahmad Khan ◽

Saleha Rehman ◽

Bushra Nabi ◽

Ashif Iqubal ◽

Nida Nehal ◽

...

Keyword(s):

Targeted Delivery ◽

Drug Loading ◽

Entrapment Efficiency ◽

Fold Increase ◽

Pharmacokinetic Studies ◽

Nanostructured Lipid Carrier ◽

Brain Delivery ◽

The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

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