Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes

Abstract Capsaicin (CAP) is an active component in Capsicum annuum L. known to have anti inflammatory and anticancer activity. CAP is highly lipophilic and suffers low bioavailability. Therefore, developing delivery systems that enhance solubility and bioavailability can provide more promising therapeutic applications for CAP. In the current work, CAP was complexed with β-cyclodextrin (βCD) to form capsaicin-in-β-cyclodextrin (CAP-in-βCD) inclusion complexes. Then, the CAP-in-βCD inclusion complexes were characterized and loaded into PEGylated liposomes using the thin-film hydration extrusion method. The size, charge, and polydispersity index (PDI) of the PEGylated liposomes were characterized. The levels of IL-8 production were quantified after treatment using array beads. The results of this work showed that the successful formation of inclusion complexes at 1:5 M ratio of CAP to βCD respectively. PEGylated liposomes loaded with βCD/CAP inclusion complexes (CAP-in-βCD-in-liposomes) have a hydrodynamic diameter of (181 ± 36) nm, zeta potential of (−2.63 ± 4.00) mV, encapsulation efficiency (EE) of (38.65 ± 3.70)%, drug loading (DL) of (1.65 ± 0.16)%, and a stable release profile. Both free CAP and liposomal CAP showed a significant reduction in the IL-8 production by the MDA-MB-231 and A549 cancer cell lines after treatment. In conclusion, a liposomal-based drug delivery system for CAP was achieved.

Download Full-text

Development of Injectable PEGylated Liposome Encapsulating Disulfiram for Colorectal Cancer Treatment

Pharmaceutics ◽

10.3390/pharmaceutics11110610 ◽

2019 ◽

Vol 11 (11) ◽

pp. 610 ◽

Cited By ~ 7

Author(s):

Mohammad Najlah ◽

Ammar Said Suliman ◽

Ibrahim Tolaymat ◽

Sathishkumar Kurusamy ◽

Vinodh Kannappan ◽

...

Keyword(s):

Colorectal Cancer ◽

Zeta Potential ◽

Cell Lines ◽

Cancer Cell ◽

Horse Serum ◽

Wild Type ◽

Pegylated Liposomes ◽

Liposomal Formulations ◽

Anti Cancer ◽

Colorectal Cancer Cell Lines

Disulfiram (DS), an anti-alcoholism medicine, shows strong anti-cancer activity in the laboratory, but the application in clinics for anti-cancer therapy has been limited by its prompt metabolism. Conventional liposomes have shown limited ability to protect DS. Therefore, the aim of this study is to develop PEGylated liposomes of DS for enhanced bio-stability and prolonged circulation. PEGylated liposomes were prepared using ethanol-based proliposome methods. Various ratios of phospholipids, namely: hydrogenated soya phosphatidylcholine (HSPC) or dipalmitoyl phosphatidylcholine (DPPC) and N-(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-PEG2000) with cholesterol were used. DS was dissolved in the alcoholic solution in different lipid mol% ratios. The size of the resulting multilamellar liposomes was reduced by high-pressure homogenization. Liposomal formulations were characterized by size analysis, zeta potential, drug loading efficiency and stability in horse serum. Small unilamellar vesicles (SUVs; nanoliposomes) were generated with a size of approximately 80 to 120 nm with a polydispersity index (PDI) in the range of 0.1 to 0.3. Zeta potential values of all vesicles were negative, and the negative surface charge intensity tended to increase by PEGylation. PEGylated liposomes had a smaller size (80–90 nm) and a significantly lower PDI. All liposomes showed similar loading efficiencies regardless of lipid type (HSPC or DPPC) or PEGylations. PEGylated liposomes provided the highest drug biostability amongst all formulations in horse serum. PEGylated DPPC liposomes had t1/2 =77.3 ± 9.6 min compared to 9.7 ± 2.3 min for free DS. In vitro cytotoxicity on wild type and resistant colorectal cancer cell lines was evaluated by MTT assay. All liposomal formulations of DS were cytotoxic to both the wild type and resistant colorectal cancer cell lines and were able to reverse chemoresistance at low nanomolar concentrations. In conclusion, PEGylated liposomes have a greater potential to be used as an anticancer carrier for disulfiram.

Download Full-text

Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells

Nanoscale ◽

10.1039/c7nr02595e ◽

2017 ◽

Vol 9 (31) ◽

pp. 11137-11147 ◽

Cited By ~ 14

Author(s):

C. Brazzale ◽

F. Mastrotto ◽

P. Moody ◽

P. D. Watson ◽

A. Balasso ◽

...

Keyword(s):

Gold Nanoparticles ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Uptake ◽

Ph Responsive ◽

Responsive Polymers ◽

Nanoparticle Surface ◽

Site Selectivity ◽

Ph Responsive Polymers

The pH-triggered display of targeting agent on nanoparticle surface controls cancer cell uptake. This enhances site-selectivity of nanosystems.

Download Full-text

Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting

Journal of Pharmaceutical Investigation ◽

10.1007/s40005-017-0329-5 ◽

2017 ◽

Vol 47 (3) ◽

pp. 203-227 ◽

Cited By ~ 47

Author(s):

Chang Hyun Kim ◽

Sang Gon Lee ◽

Myung Joo Kang ◽

Sangkil Lee ◽

Young Wook Choi

Keyword(s):

Surface Modification ◽

Cancer Cell ◽

Drug Targeting ◽

Specific Drug

Download Full-text

Synthesis and Evaluation of 198Au/PAMAM-MPEG-FA against Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200220113452 ◽

2020 ◽

Vol 20 (10) ◽

pp. 1250-1265

Author(s):

Reza Rezaei ◽

Simin Janitabar Darzi ◽

Mahnaz Yazdani

Keyword(s):

Breast Cancer ◽

Cancer Cell ◽

Therapeutic Potential ◽

Analytical Techniques ◽

Cell Uptake ◽

Breast Adenocarcinoma ◽

Human Breast ◽

Clinical Investigations ◽

Anti Cancer

Background: There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines. Objective: The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here. Methods: The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated. : Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell). Results: The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent. Conclusion: On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.

Download Full-text