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The positively-charged peptide antp derived from Antennapedia transcription protein is demonstrated to mediate the liposome translocation across the cell membrane. In the current investigation, we prepared a stable liposomal doxorubicin (Dox) formulation and targeted it with the antp peptide from 0 to 200 ligand/liposome. These antp-containing liposomes were investigated in terms of physical stability on storage in the refrigerator and upon incubation in blood. Also, other features like cell binding, uptake, biodistribution, and treatment efficiency were evaluated in C26 colon carcinoma BALB/c mice. The Antp in liposomes resulted in enhanced particle growth with the development of the enormously large liposomes from 2000 to 6000 nm. Upon incubation in blood, these large liposomes were removed. The antp also enhanced the cell binding affinity and cell uptake rate of the liposomes and resulted in the restriction of the cancer cell proliferation, but it failed to improve the chemotherapeutic property of the Dox-liposome. The i.v. injection of antp-liposomes (15 mg Dox/kg) caused severe body weight loss and early death incidence due to probably increased toxicity. The antp targeting offered no advantage to the Dox-liposome in the delivery of Dox to the tumor, and failed to enhance the treatment efficiency of the liposomes., (© 2021 American Institute of Chemical Engineers.)

The aim of this study was to surface-functionalize PEGylated liposomal doxorubicin (PLD) using anti-p32 CGKRK peptide to evaluate its anti-angiogenic and anti-tumour activities. CGKRK was conjugated to DSPE-mPEG 2000 -maleimide and post-inserted into PLD at 25, 50, 100, 200 and 400 peptides per each liposome and characterised for their size, zeta potential, drug loading, release properties; and cell binding, cell uptake and cytotoxicity on three C26, 4T1 and human umbilical vein endothelial cell (HUVEC) cell lines. The in vitro results indicated the better efficiency of the PLD-100 (PLD with 100 CGKRK) formulation on 4T1 and HUVEC cell lines. The results of anti-tube formation and spheroid assay indicated the efficiencies of the PLD-100 formulation compared with Caelyx ® in vitro . The in vivo studies indicated the higher tumour accumulation of PLD-100 formulation in comparison with Caelyx ® which also implied the higher survival rates in mice treated with PLD-100 formulation. Histological evaluations demonstrated that PLD-100 had no side-effects on major organs. In conclusion, the results of this study indicated that PLD-CGKRK- could efficiently target endothelial and tumour parenchymal cells which enhance the therapeutic efficacy of PLD and merits further investigation.

To overcome the lack of selectivity and nonspecific biodistribution of drugs in the body, targeted delivery of chemotherapeutic agents with aptamers is a very effective method. In this strategy, aptamers could be specifically identified and attach to targeted molecules on the cancerous cells and deliver the chemotherapeutic agents to desired tissue with minimal or no damage to the normal cells. In this study, we designed anti-epithelial cell adhesion molecule (EpCAM) RNA aptamer conjugated PEGylated liposomal doxorubicin (ER-lip) to investigate its in vitro and in vivo anticancer abilities. Data showed that EpCAM aptamer was able to enhance cell uptake and cytotoxic effects of Dox in C26 cell line. The biodistribution study indicated that ER-lip enhanced the tumor accumulation of Dox compared to Caelyx. Also, double staining of isolated tumor cells with anti-CD44-PE-cy5 and anti-EpCAM Cy-7 antibodies indicated that tumor cells expressed a high level of EpCAM + CD44 + cells (p ≤ .001) compared to cultured C26 cell line. in vivo results showed that ER-lip promoted survival and reduced tumor growth rate in animal model compared to Caelyx. In conclusion, these results suggested that the ER-lip could be served as promising formulation for the treatment of cancers with the high expression of EpCAM., (© 2020 American Institute of Chemical Engineers.)

Background: Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. Objective: In this study, nano-niosomes were introduced for improving therapeutic index of DXL. Material and Methods: In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. Results: DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Conclusion: Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Liposome nanoparticles have emerged as promising drug delivery systems due to their unique properties. Assessing particle size and polydispersity index (PDI) is critical for evaluating the quality of these liposomal nanoparticles. However, optimizing these parameters in a laboratory setting is both costly and time-consuming. This study aimed to apply a machine learning technique to assess the impact of specific factors, including sonication time, extrusion temperature, and compositions, on the size and PDI of liposomal nanoparticles. Liposomal solutions were prepared and subjected to sonication with varying values for these parameters. Two compositions: (A) HSPC:DPPG:Chol:DSPE-mPEG2000 at 55:5:35:5 molar ratio and (B) HSPC:Chol:DSPE-mPEG2000 at 55:40:5 molar ratio, were made using remote loading method. Ensemble learning (EL), a machine learning technique, was employed using the Least-squares boosting (LSBoost) algorithm to accurately model the data. The dataset was randomly split into training and testing sets, with 70% allocated for training. The LSBoost algorithm achieved mean absolute errors of 1.652 and 0.0105 for modeling the size and PDI, respectively. Under conditions where the temperature was set at approximately 60 °C, our EL model predicted a minimum particle size of 116.53 nm for composition (A) with a sonication time of approximately 30 min. Similarly, for composition (B), the model predicted a minimum particle size of 129.97 nm with sonication times of approximately 30 or 55 min. In most instances, a PDI of less than 0.2 was achieved. These results highlight the significant impact of optimizing independent factors on the characteristics of liposomal nanoparticles and demonstrate the potential of EL as a decision support system for identifying the best liposomal formulation. We recommend further studies to explore the effects of other independent factors, such as lipid composition and surfactants, on liposomal nanoparticle characteristics. [ABSTRACT FROM AUTHOR]

Vitamin C, as an antioxidant additive in pharmaceutical and food products, is susceptible to environmental conditions, and new design strategies are needed to enhance its stability. The aim of this study is to prepare vitamin C proliposome using film deposition on the carrier by applying different factors, and optimise the characteristics of the obtained powder using the design expert® software. The optimised formulation demonstrated acceptable flowability with 20% vitamin C loading. This formulation released about 90% vitamin C within 2 h and showed higher (1.7-fold) in-vitro antioxidant activity. Ex-vivo antioxidant activity was 1.9 and 1.6 times higher in brain and liver cells, respectively. A 27% reduction in malondialdehyde (MDA) level of liver cell was obtained comparing free vitamin C. Therefore, this study results suggest that the vitamin C-encapsulated proliposome powder might be an appropriate carrier for oral drug delivery of vitamin C with better antioxidant efficacy. [ABSTRACT FROM AUTHOR]