Liposomski sustavi za isporuku lijekova Klinička primjena

Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.Od 1970. godine liposomi se intenzivno istražuju kao nosači ljekovitih tvari za isporuku u određene dijelova organizma. Unapređenje i razvoj liposoma omogućili su njihovu kliničku primjenu u terapiji određenih bolesti. Na tržištu je prisutan određen broj ljekovitih oblika na bazi liposoma, a dio je još u kliničkim pokusima. Svi su oni rezultat boljeg razumjevanja raspodjele liposoma i interakcija između lipida i ljekovite tvari. Moguće je pripremiti liposome koji se mogu usmjeriti u određena tkiva, stanice ili međustanične prostore, sa ili bez vezanih molekula za prepoznavanje na površini membrane. Ovaj revijalni članak uglavnom obuhvaća liposome za terapiju karcinoma, bakterijskih i gljivičnih infekcija jer je u tim područjima primjena liposoma najviše opravdana i stoga najviše istraživana. Osim toga, pravilnim izborom vektora za prijenos gena i načina isporuke može se povećati i učinkovitost prijenosa gena

Novel drug delivery systems in topical treatment of psoriasis: Rigors and vigors

Psoriasis is a chronic inflammatory skin disorder that may drastically impair the quality of life of a patient. Among the various modes of treatments for psoriasis, topical therapy is most commonly used in majority of patients. The topical formulations based on conventional excipients could serve the purpose only to a limited extent. With the advent of newer biocompatible and biodegradable materials like phospholipids, and cutting-edge drug delivery technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions, and nanoemulsions, the possibility to improve the efficacy and safety of the topical products has increased manifold. Improved understanding of the dermal delivery aspects and that of designing and developing diverse carrier systems have brought in further novelty in this approach. Substantial efforts and the consequent publications, patents and product development studies on the subject are the matter of interest and review of this article. However, majority of the work is related to the preclinical studies and demands further clinical assessment in psoriasis patients

Topical treatment in vitiligo and the potential uses of new drug delivery systems

Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream), trioxsalen (solution), corticosteroids (gel, cream, ointment and solution) and calcineurin inhibitors (ointment and cream). Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient compliance. Novel drug delivery strategies can play a pivotal role in improving the topical delivery of various drugs by enhancing their epidermal localization with a concomitant reduction in their side-effects and improving their effectiveness. The current review emphasizes the potential of various phospholipid based carriers viz. liposomes, transferosomes, ethosomes, lipid emulsions, solid lipid nanoparticles and organogels in optimizing and enhancing the topical delivery of anti-vitiligo agents, whilst reducing the side effects of drugs commonly used in its topical treatment

Bacterial count (CFU/ml) on different days of incubation of a 7 day biofilm of <i>K</i>. <i>pnuemoniae</i> B5055 in a microtiter plate following treatment with plain liposomes (empty lipoosmes as control), antibiotic (amikacin at 40 μg/ml), non-entrapped phages (MOI = 1) and liposome entrapped phages (MOI = 1).

<p>All values represent the mean ± SEM, calculated from two independent experiments, each performed in duplicate on different occasions.</p

Encapsulation of Bacteriophage in Liposome Accentuates Its Entry in to Macrophage and Shields It from Neutralizing Antibodies

<div><p>Phage therapy has been a centre of attraction for biomedical scientists to treat infections caused by drug resistant strains. However, ability of phage to act only on extracellular bacteria and probability of interference by anti-phage antibodies <i>in vivo</i> is considered as a important limitation of bacteriophage therapy. To overcome these hurdles, liposome were used as delivery vehicle for phage in this study. Anti-phage antibodies were raised in mice and pooled serum was evaluated for its ability to neutralize free and liposome entrapped phage. Further, ability of phage and liposome-entrapped phage to enter mouse peritoneal macrophages and kill intracellular <i>Klebsiella pneumoniae</i> was compared. Also, an attempt to compare the efficacy of free phage and liposome entrapped phage, alone or in conjunction with amikacin in eradicating mature biofilm was made. The entrapment of phage in liposome provided 100% protection to phage from neutralizing antibody. On the contrary un-entrapped phage got neutralized within 3 h of its interaction with antibody. Compared to the inability of free phage to enter macrophages, the liposome were able to deliver entrapped phage inside macrophages and cause 94.6% killing of intracellular <i>K</i>. <i>pneumoniae</i>. Liposome entrapped phage showed synergistic activity along with amikacin to eradicate mature biofilm of <i>K</i>. <i>pneumoniae</i>. Our study reinforces the growing interest in using phage therapy as a means of targeting multidrug resistant bacterial infections as liposome entrapment of phage makes them highly effective <i>in vitro</i> as well as <i>in vivo</i> by overcoming the majority of the hurdles related to clinical use of phage.</p></div

Comparison of effect of neutralizing antibodies on phage and liposome entrapped phage.

<p>Comparison of effect of neutralizing antibodies on phage and liposome entrapped phage.</p

Particle size distribution and PDI of liposomal formulation of phage.

<p>Particle size distribution and PDI of liposomal formulation of phage.</p

Comparison of percent killing of intracellular bacteria when treated with phage and liposome entrapped phage.

<p>Comparison of percent killing of intracellular bacteria when treated with phage and liposome entrapped phage.</p

Percent bacterial uptake and killing by mouse peritoneal macrophages at different time intervals.

<p>All values represent the mean ± SEM, calculated from two independent experiments, each performed in duplicate on different occasions. SEM represent the 95% confidence interval. Confidence interval is calculated as SEM * 3.18. Raw data is available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153777#pone.0153777.t002" target="_blank">Table 2</a>.</p