Comparative study of liposomes,transfersomes, ethosomes and cubosomes for transcutaneous immunisation: characterisation and in vitro skin penetration

Objectives Lipid colloidal vaccines, including liposomes, transfersomes, ethosomes and cubosomes, were formulated, characterised and investigated for their ability to enhance penetration of a peptide vaccine through stillborn piglet skin in vitro. Methods Liposomes and transfersomes were formulated using a film‐hydration method, ethosomes using a modified reverse phase method and cubosomes using a lipid precursor method. The size, zeta potential, peptide loading and interfacial behaviour of the formulations were characterised. Skin penetration studies were performed using Franz diffusion cells with piglet skin as the membrane. The localization of peptide in the skin was examined using confocal laser scanning microscopy. Key finding The various formulations contained negatively charged particles of similar size (range: 134–200 nm). Addition of the saponin adjuvant Quil A to the formulations destabilised the monolayers and reduced peptide loading. Cubosomes and ethosomes showed superior skin retention compared with the other systems. Confocal laser scanning microscopy showed greater peptide penetration and accumulation in the skin treated with cubosomes and ethosomes. With the other systems peptide was only located in the vicinity of the hair follicles and within the hair shaft. Conclusions We conclude from the in‐vitro studies that cubosomes and ethosomes are promising lipid carriers for transcutaneous immunisation.     

Transcutaneous immunization using microneedles and cubosomes: Mechanistic investigations using Optical Coherence Tomography and Two-Photon Microscopy

Transcutaneous (TCI) immunization is a novel vaccination approach that provides many advantages over traditional parenteral vaccination. However, a major barrier to TCI is mediating penetration of vaccine antigens through the stratum corneum (SC) to the deeper tissue layers. Many approaches have been investigated for enhancing drug penetration into the skin including microneedles (MNs) to transiently breach the SC barrier and incorporation of vaccines into penetration-enhancing delivery systems. This study utilized MNs and a lipid-based colloidal delivery system (cubosomes) as a synergistic approach for the delivery of vaccines through the skin. The penetration and permeation of the peptide antigen into and through skin were analysed quantitatively and qualitatively using techniques including Optical Coherence Tomography and two-photon microscopy. It was found that while the use of MNs increased the permeation of an aqueous peptide mixture through skin, cubosome-formulated peptide and cubosomes were retained in the skin. Therefore, it is proposed that a combined approach using MNs and cubosomes will be an efficient system for the local delivery of antigen to immunocompetent cells in the skin.     

Sexuality and Management of Benign Prostatic Hyperplasia with Alfuzosin: SAMBA Thailand

IntroductionBenign prostatic hyperplasia (BPH) is a common condition among elderly men. The aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life (QoL) and to prevent complications.AimThe primary objective was to assess the effect on ejaculatory dysfunction (EjD) of 6 months treatment with alfuzosin (XATRAL) 10 mg once daily (OD) in men with LUTS suggestive of BPH in Thailand. Secondary objectives were to evaluate the efficacy of alfuzosin on LUTS, bother score (International Prostate Symptom Score [IPSS] 8th question), erectile dysfunction (ED), onset of action, and tolerability.MethodsOverall, 99 men with moderate to severe LUTS suggestive of BPH (mean IPSS 18.9, bother score 4.3) were enrolled in an open-label study. Sexual function was evaluated at baseline and after 6 months treatment, using the International Index of Erectile Function-5 and the Male Sexual Health Questionnaire (MSHQ) ejaculation score, a new validated questionnaire assessing seven EjD symptoms.Main Outcome MeasureThe main outcome measure is mean change from baseline to the end of treatment in the MSHQ Ejaculation score.ResultsMHSQ ejaculation score significantly improved from 23.09 at baseline to 21.54 at 6 months (P = 0.022). Overall, 70% of patients perceived an improvement in LUTS within 1 week (36.3% within 3 days). IPSS total score significantly improved from 18.93 at baseline to 9.59 at 6 months (P < 0.001). IPSS voiding and irritative subscores also significantly improved. The percentage of patients with moderate or severe ED decreased from 35.3% at baseline to 21.8% at 6 months. Most adverse events were dizziness (3%) and orthostatic hypotension (1%) with minor intensity. No significant change in blood pressure and heart rate was observed.ConclusionsAlfuzosin 10 mg OD administered for 6 months provides a marked and rapid (within 1 week) improvement in LUTS and bother score while improving both ED and EjD. Leungwattanakij S, Watanachote D, Noppakulsatit P, Petchpaibuol T, Choeypunt N, Tongbai T, Wanamkang T, Lojanapiwat B, Permpongkosol S, Tantiwong A, Pripatnanont C, Akarasakul D, Kongwiwatanakul S, and Chotikawanich E. Sexuality and management of benign prostatic hyperplasia with alfuzosin: SAMBA Thailand.