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Nano-drug delivery systems have opened new pathways for tumor treatment by overcoming some of the limitations of conventional drugs, such as physiological degradation, short half-life, and rapid release. Liposomes are promising nanocarrier systems due to their biocompatibility, low toxicity, and high inclusivity, as well as their enhanced drug bioavailability. Various strategies for active targeting of liposomal formulations have been investigated to achieve the highest drug efficacy. This review aims to summarize current developments in novel liposomal formulations, particularly ligand-targeted liposomes (such as folate, transferrin, hyaluronic acid, antibodies, aptamer, and peptide, etc.) used for the therapy of various cancers and provide an insight on the challenges and future of liposomes for scientists and pharmaceutical companies.

This study aims to develop a multifunctional liposomal radiosensitizer to destroy more tumor cells by using lower radiation doses compared to clinically used 6 MV X-ray doses. To achieve this aim, first Chlorine-e6 (Ce6) was covalently bound to functional groups of outer surfaces of quantum dots (QDs) through EDC/NHS reactions. Then, QDs-Ce6 conjugate loaded, nanosized, PEG-coated, and tumor-specific folic acid-modified immunoliposome dispersions were prepared by film method. Enhanced anti-proliferation activity of free and liposomal conjugate against 4T1 (murine breast cancer) cell lines was investigated at different X-ray doses (5, 10, 15, and 20 Gy). As a result, the best radiosensitizer effect was observed at a 5 Gy X-ray dose and it was found that following the X-ray irradiation, immunoliposome dispersions containing QDs-Ce6 conjugate killed 26.8 ± 1.7% more cancer cells than radiation alone.

The in-vitro cytotoxicity, in-vitro permeability and in-vivo pharmacokinetics of a BCS Class-II drug - rufinamide - in a 3DP tablet formulation were evaluated. The cytotoxicity of the 3DP tablet formulation was evaluated with an MTT test; in-vitro permeability was evaluated with a Caco-2 cell culture study; and in-vivo pharmacokinetics were evaluated in Wistar albino male rats. The pharmacokinetic studies were performed following a two-sequence and single-period design approach. The highest Caco-2 permeability was obtained with the 3DP tablet formulation; and the highest cell viability was achieved with the 3DP tablet in both the Hep G2 and Caco-2 cell lines. In the in-vivo pharmacokinetic study, AUC and Cmax values were higher in the 3DP tablet formulation than in the Inovelon® film tablet at a 40 mg/kg dose. Thanks to the increased solubility of the active substance, higher in-vitro permeability and in-vivo absorption were achieved with the 3DP tablet formulation, and with lower cytotoxicity. Based on these promising findings, the 3DP tablet formulation can be considered an effective lower-dose treatment than commercial preparations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Swallowing oral solid dosage forms is challenging in patients with dysphagia who are at risk of aspiration or choking. The most common method to facilitate drug administration in dysphagia patients is to mix the powdered drug with a small amount of thickened water, however little is known about the effects of this method on in vivo bioavailability of drugs. This study aimed to evaluate the impact of thickened liquids on dissolution rate and bioavailability of levetiracetam as a model drug. Powdered commercial tablets of levetiracetam, carbamazepine, atenolol and cefixime were mixed with water thickened with two commercial thickeners, modified maize starch (MS) and xanthan gam (XG), at three thickness levels: nectar, honey and pudding in test groups, and mixed with only water in the control group. At the first stage, the effects of thickened water on in vitro drug release of 4 drugs (levetiracetam, carbamazepine, atenolol and cefixime) were tested by using dialysis membrane method. Addition of both thickeners significantly reduced the release of three drugs compared to the control group, except carbamazepine. Levetiracetam which had the highest solubility was chosen as the model drug for in vivo experiments. In the second stage, New Zealand albino female rabbits (n=24) were divided into two groups as: control group (water+drug, n=6) and test group (thickened water+drug, n=18). Powdered levetiracetam tablets were mixed with water thickened with XG (n=9, 1.2%, 2.4%, 3.6%) and MS (n=9, 4%, 6%, 8%) at three thickness levels and administered to the rabbits by intragastric gavage. Blood samples were collected at 9 time points following administration. After two-weeks of wash-out, test groups were crossed over and sample collection was repeated. Blood samples were analysed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). An in vitro-in vivo correlation (IVIVC) model was developed using in vitro drug dissolution (%) and in vivo plasma concentrations of levetiracetam for control group and test groups. The peak plasma concentration (C max ) was lower and time to reach C max (t max ) was relatively higher in test groups compared to control group. The lowest C max was detected at the highest thickness level, however, the differences between groups were not statistically significant (p=0.117 and p=0.495 for C max and t max , respectively). No significant difference in total amount of levetiracetam absorbed (AUC) was found between groups (p=0.215 and p=0.183 for AUC infinity and AUC last , respectively). The comparisons according to the type of thickener also revealed that pharmacokinetic parameters did not significantly differ between groups, except for a significantly lower C max when drug was mixed with MS-thickened water at nectar consistency (1.2%) compared to drug mixed with XG (4%) at the same thickness level (p=0.038). A good correlation was observed between in vitro and in vivo data, which was characterized by higher r 2 values as the concentration of the thickening agents was increased, but not for all thickness levels studied, indicating an inability of this in vitro model to fully predict the in vivo response. These results suggest that regardless of the thickness level, the administration of levetiracetam with two commercial thickening agents commonly used in dysphagia for safe swallowing, do not affect the pharmacokinetic efficiency and thus, the bioavailability of the drug., (Copyright © 2022. Published by Elsevier B.V.)

Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1-60.0 μg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10 -6 cm/s., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cancer is the second leading cause of death worldwide, and the search for specialised therapy options has been a challenge for decades. The emergence of active targeted therapies provides the opportunity to treat cancerous tissues without harming healthy ones due to peculiar physiological changes. Herein, peptides and peptide analogs have been gaining a lot of attention over the last decade, especially for the on-site delivery of therapeutics to target tissues in order to achieve efficient and reliable cancer treatment. Combining peptides with highly efficient drug delivery platforms could potentially eliminate off-target adverse effects encountered during active targeting of conventional chemotherapeutics. Small size, ease of production and characterisation, low immunogenicity and satisfactory binding affinity of peptides offer some advantages over other complex targeting moiety, no wonder the market of peptide-based drugs continues to expand expeditiously. It is estimated that the global peptide drug market will be worth around USD 48.04 billion by 2025, with a compound annual growth rate of 9.4%. In this review, the current state of art of peptide-based therapeutics with special interest on tumour targeting peptides has been discussed. Moreover, various active targeting strategies such as the use functionalised peptides or peptide analogs are also elaborated.