A number of amphiphilic cyclic peptides—[FR]₄, [WR]₅, and [WK]₅—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]₅, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]₅ with lipid DOPE significantly enhanced the efficiency of siRNA delivery by up to ~2-fold compared to peptide alone. Based on the data indicating the efficiency of [WR]₅ in siRNA delivery, peptides containing arginine residues on the ring and tryptophan residues on the side chain, [R₆K]W₆ and [R₅K]W₅, were also evaluated, and demonstrated improved delivery of siRNA. The presence of DOPE again enhanced the siRNA delivery in most cases. [WR]₅, [R₅K]W₅, and [R₆K]W₆ did not show any significant toxicity in MDA-MB-231, MDA-MB-468, and AU565 WT cells at N/P ratios of 20:1 or less, in the presence and absence of DOPE. Silencing of kinesin spindle protein (KSP) and Janus kinase 2 (JAK2) was evaluated in MDA-MB-231 cells in the presence of the peptides. The addition of DOPE significantly enhanced the silencing efficiency for all selected peptides. In conclusion, peptides containing tryptophan and arginine residues were found to enhance siRNA delivery and to generate silencing of targeted proteins in the presence of DOPE.

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. A modified version of P6 peptide and colchicine-P6 peptide conjugate were synthesized using Fmoc/tBu solid-phase and solution-phase chemistry, respectively. A glutaryl amide was used as a linker. The P6 peptide was evaluated for its binding to CD44, association, and internalization by macrophages. Cytotoxic effects of P6 peptide, colchicine, and colchicine-P6 peptide on macrophages were compared and the inhibition of ROS generation and interleukin-8 (IL-8) secretion in MSU-stimulated macrophages treated with P6 peptide, colchicine, or colchicine-P6 peptide was studied. We confirmed that the P6 peptide binds to CD44 and its association and internalization by macrophages were CD44-dependent. Colchicine (1, 10, and 25 μM) demonstrated a significant cytotoxic effect on macrophages while the P6 peptide and colchicine-P6 peptide conjugate (1, 10 and 25 μM) did not alter the viability of the macrophages. The P6 peptide (10 and 25 μM) reduced ROS generation and IL-8 secretion mediated by a reduction in MSU phagocytosis by macrophages. The colchicine-P6 peptide significantly reduced ROS generation and IL-8 secretion compared to the P6 peptide alone at 1 and 10 μM concentrations. Conjugation of colchicine to the P6 peptide reduced the cytotoxic effect of colchicine while preserving its anti-inflammatory activity.

After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a variety of molecularly targeted drugs to clinical practice, chemotherapy is still at the forefront of the battle against cancer. In this manuscript, we review the major mechanisms involved in MDR and resistance against different categories of molecularly targeted drugs separately, and review some of the strategies studied to overcome the resistance against cancer therapy. While MDR mechanisms have been reviewed previously, the molecular mechanisms of resistance to the latest generations of anticancer drugs are rarely reviewed as a group, and the connection between the two categories of resistance is often missing in this type of publication. Our aim is to illustrate a comprehensive picture of what the landscape of cancer treatment is today with respect to resistance. While this picture seems bleak, and it is the common belief that resistance is inevitable, understanding the mechanisms involved could potentially lead to more efficient approaches to overcoming this so far unbeatable obstacle.

Background Prescriptions, medicolegal documents issued by physicians to patients, must be written accurately and clearly, contain all the required information, and adhere to the guidelines for prescription writing. In eastern Libya, most prescriptions are handwritten. Incomplete prescriptions might lead to serious medication errors. Aim The aim of this article was to assess the completeness of handwritten prescriptions issued by physicians working in eastern Libya. Method A total of 1,080 handwritten prescriptions were collected from pharmacies in different parts of the city of Derna and its suburbs in eastern Libya. After the exclusion of three prescriptions that were defined as illegible by the researchers, the 1,077 remaining prescriptions were examined for completeness against a checklist designed according to the guidelines of the World Health Organization (WHO). Results Most of the prescriptions (84.12%) did not contain the name of the prescribing physician. The patient's name was not mentioned on 16.06% of the prescriptions. Patient-related information was missing in most of the prescriptions. Most of the physicians (91.27%) prescribed drugs using their trade names. Drug strength, route of drug administration, and duration of therapy were absent in 29.61, 87, and 56.17% of the prescriptions, respectively. Only 26% of the prescriptions contained the date. Conclusion Most of the prescriptions inspected in this study had some deficiencies and did not adhere to the WHO guidelines.

Improper disposal of unused or expired medications presents a serious threat to both environmental and public health. This study aimed to conduct an initial assessment of the knowledge, attitudes, and disposal practices related to medications among an online, convenience sample of the Libyan population. A descriptive cross-sectional online survey was conducted from December 13–22, 2024, using a structured, 20-item questionnaire. The tool, adapted from a validated bilingual questionnaire, comprised four sections: demographics, knowledge, attitudes, and disposal practices. Knowledge was assessed via three items scored as correct (2 points), uncertain (1 point), or incorrect (0 points), with total scores (0–6) categorized as poor (0–2), moderate (3–4), or high (5–6) knowledge. Disposal practices were evaluated through two items, where a correct response scored 2 points and an incorrect response 0 points, categorizing a total score of 4 as positive practice and a score of 0 to 2 as negative practice. Data were analyzed using SPSS version 23, employing descriptive statistics and chi-square tests to examine associations. The sample of 478 respondents was predominantly female (66.7%), young (56.9% aged 18–25 years), and highly educated (79.7% holding a university degree). Among 478 participants, 81% demonstrated a high level of knowledge about medication safety and expiration. Positive attitudes toward proper disposal were expressed by 55.6%, and were significantly associated with being female and employed. However, only 5.0% of respondents followed the recommended practice of returning expired medications to a pharmacy. No significant associations were found between disposal practices and demographic variables. This study highlights widespread unsafe disposal practices despite relatively high levels of knowledge. These findings highlight the urgent need for national policies that establish clear guidelines, promote public education, and provide accessible systems for safe medication disposal in Libya.