Surface modified nanoliposome formulations provide sustained release for 5-FU and increase cytotoxicity on A431 cell line.

Malignant melanoma is a type of skin cancer with high risk of metastasis. 5-Fluorouracil is commonly used for treatment of skin cancer, however its penetration through the skin is found to be insufficient in some cases. Therefore, we optimized its pharmacokinetics by fabricating 5- Fluorouracil-loaded nanoliposome formulations modified with Poly-L-lysine coating. 5-Fluorouracil-loaded nanoliposome formulations were prepared using dipalmitoylphosphatidylcholine, dicethylphosphate and cholesterol having encapsulation efficiency of 45 ± 9.61%. The particle size, zeta potential, polydispersity index and encapsulation rate of the prepared formulation was found to be 237.9 ± 0.986 nm, 41.4 ± 1.060 mV, 0.233 ± 0.019 and 88.2 ± 7.85%, respectively. Surface characterization, molecular structure and thermal property illumination of the formulations were performed alongside stability studies. The In-vitro release of 5-FU from Lipo-FU6 and PLL-1 formulations was investigated by dialysis membrane method. Within the first 12 hours, the percentage release of 5-FU from Lipo-FU6 and PLL-1 formulations was observed to be 47.17% and 20.84%, respectively. Moreover, the cytotoxicity study on A431 epidermal carcinoma cell lines has revealed that 5-FU-loaded formulations were toxic to cells unlike the 5-FU free formulations. In conclusion, PLL coated nanoliposome formulations showed a potential to be an effective option for further combined drug/gene therapy applications.

Liposome-based combination therapy for acne treatment.

Acne vulgaris is one of the most common chronic diseases worldwide with the high prevalence ratio of about 80-85% in patients who are in puberty period. For the treatment options, many conventional dosage forms are available; however, existing limitations of systemic administration of drugs (oral antibiotics), such as adverse events and resistance, led for seek of new formulation options. In this study, liposomes containing tetracycline HCl and tretinoin were prepared by the film formation method. In vitro characterization studies revealed that liposomes (111.10 ± 8.02 nm; P.D.I.=0.198 ± 0.03; Z.P.=25.83 ± 0.40 mV) with an encapsulation efficiency more than 80% for both APIs were formulated. In order to maintain a suitable viscosity for topical application, optimized liposomal formulations were dispersed in carbopol-based gel. In vitro release of APIs was sustained for 24 hours with released amounts of 56.44% and 58.44% for tetracycline HCl and tretinoin, respectively. Stability evaluation of both liposomes and liposomes in hydrogels was investigated for 6 months at 4 °C and 25 °C; and no statistically significant change was observed in terms of particle size, zeta potential, encapsulation efficiency, appearance, pH, and viscosity. Cytotoxicity tests confirmed the nontoxic structure of liposomal gel formulations on mice fibroblast cells. In addition, antibacterial efficacy has been proven with Staphylococcus aureus and Streptococcus epidermidis strains as well as the effect on biofilm formation and eradication. As a result, we hereby presented a new combination drug product, which consists of dual active ingredients having comedolytic and bacteriostatic effects in a single, safe, and stable liposome formulation.

Targeted Therapies for Pancreatic Cancer and Hurdles Ahead.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNA-based therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.