Željka Vanić - Academia.edu (original) (raw)

Papers by Željka Vanić

Biomaterials advances, Feb 1, 2023

The eradication of bacteria embedded in biofilms is among the most challenging obstacles in the m... more The eradication of bacteria embedded in biofilms is among the most challenging obstacles in the management of chronic wounds. These biofilms are found in most chronic wounds; moreover, the biofilm-embedded bacteria are considerably less susceptible to conventional antimicrobial treatment than the planktonic bacteria. Antimicrobial peptides and their mimics are considered attractive candidates in the pursuit of novel therapeutic options for the treatment of chronic wounds and general bacterial eradication. However, some limitations linked to these membrane-active antimicrobials are making their clinical use challenging. Novel innovative delivery systems addressing these limitations represent a smart solution. We hypothesized that incorporation of a novel synthetic mimic of an antimicrobial peptide in liposomes could improve its anti-biofilm effect as well as the antiinflammatory activity. The small synthetic mimic of an antimicrobial peptide, 7e-SMAMP, was incorporated into liposomes (~280 nm) tailored for skin wounds and evaluated for its potential activity against both biofilm formation and eradication of pre-formed biofilms. The 7e-SMAMP-liposomes significantly lowered inflammatory response in murine macrophages (~30 % reduction) without affecting the viability of macrophages or keratinocytes. Importantly, the 7e-SMAMP-liposomes completely eradicated biofilms produced by Staphylococcus aureus and Escherichia coli above concentrations of 6.25 μg/mL, whereas in Pseudomonas aeruginosa the eradication reached 75 % at the same concentration. Incorporation of 7e-SMAMP in liposomes improved both the inhibition of biofilm formation as well as biofilm eradication in vitro, as compared to non-formulated antimicrobial, therefore confirming its potential as a novel therapeutic option for bacteria-infected chronic wounds.

Carbohydrate Research, 2016

Liposomi (fosfolipidne vezikule) su u dosadasnjim istraživanjima pokazali veliki potencijal za po... more Liposomi (fosfolipidne vezikule) su u dosadasnjim istraživanjima pokazali veliki potencijal za postizanje kontrolirane i ucinkovite dostave lijekova u kožu. Međutim, topikalna primjena liposoma na kožu i sluznice može biti ogranicena njihovom tekucom prirodom, zbog cega je prikladno uklapanje liposoma u polucvrste podloge (1). Osim utjecaja na viskoznost i konzistenciju pripravka, podloge odgovarajucih svojstava doprinose fizickoj stabilnosti liposoma, te mogu utjecati na farmakokinetska svojstva uklopljenog lijeka, njegovo oslobađanje i penetraciju kroz rožnati sloj kože. Buduci da interakcije između kože, podloge i uklopljenog lijeka mogu znacajno utjecati na konacni terapijski ucinak, odabir podloge odgovarajucih svojstava kljucan je cimbenik u optimiziranju terapijske ucinkovitosti formulacija liposomi-u-podlozi (2). Ciljevi ovog rada bili su priprema i karakterizacija liposoma za dermalnu primjenu, uklapanje liposoma u prikladne podloge, te ispitivanje oslobađanja lijeka iz dobivenih formulacija liposomi-u-podlozi. Deformabilni, propilenglikol i konvencionalni liposomi s uklopljenim hidrofilnim modelnim lijekom diklofenaknatrijem pripremljeni su tzv. film metodom. Srednji promjer, indeks polidisperznosti i zeta potencijal liposoma određeni su fotonskom korelacijskom spektroskopijom. Nakon odjeljivanja neuklopljenog od liposomskog (uklopljenog) lijeka, spektrofotometrijski je određen sadržaj diklofenaknatrija uklopljenog u liposome, te uspjesnost uklapanja lijeka (3). Liposomi su potom umijesani u 2 razlicite podloge, karbopolski hidrogel i baznu kremu (U/V emulzija), te su provedena ispitivanja oslobađanja lijeka in vitro primjenom Franz difuzijske celije. Ispitivanja su provedena pri temperaturi od 32 ˚C koristenjem celulozno-nitratnih membrana. Akceptorski odjeljak (16 ml) sadržavao je demineraliziranu vodu, a kolicina oslobođenog diklofenaknatrija u određenim vremenskim intervalima određivana je spektrofotometrijski. Ispitivanja oslobađanja diklofenaknatrija iz razlicitih vrsta liposoma uklopljenih u razlicite dermalne podloge in vitro pokazala su produženo i kontrolirano oslobađanje lijeka iz svih testiranih formulacija u odnosu na kontrolu (vodena otopina lijeka u podlozi). Na profil oslobađanja lijeka iz liposoma uklopljenih u podloge znacajno je utjecao sastav samih vezikula, ali i svojstva podloge. Konvencionalni liposomi pokazali su sporije oslobađanje lijeka od oba tipa elasticnih vezikula, neovisno o koristenoj podlozi. Usporedba dviju koristenih dermalnih podloga, pokazala je brže oslobađanje lijeka iz hidrogela nego iz bazne kreme. S obzirom na dobivene rezultate, optimalnom formulacijom za dermalnu dostavu hidrofilnog lijeka pokazali su se propilenglikol liposomi uklopljeni u hidrogel.

Mucoadhesive drug delivery systems provide enhanced retention at defined sites, including vagina,... more Mucoadhesive drug delivery systems provide enhanced retention at defined sites, including vagina, longer residence time of delivery system-associated drug, offer potential for targeting to particular tissue, and, if with controlled release features, may lead to the reduction in administration frequency and comparable reduction in treatment cost. At the macroscale, vaginal mucus behaves as a non-Newtonian fluid, whereas at the nanoscale, it behaves as a low viscosity flui . One of the very important features, often neglected in the development of delivery systems for vaginal administration, is microviscosity of mucus. In order to optimize mucoadhesive delivery systems for vaginal therapy, in respect to their residence time and stability in vaginal environment, we focused on the properties of mucoadhesive polymer used in delivery system. Chitosan and pectin, two natural origin polymers, were selected due to their confirmed mucoadhesiveness. Both polymers appear in different molecular weights and degrees of deacetylation/metoxylation (DD/DM) which affect their physicochemical properties and are expected to affect mucoadhesiveness of the delivery system. Metronidazole was used as model drug and was entrapped in phosphatidylcoline (PC) liposomes of various sizes. Particle size distributions, entrapment efficiency, stability in simulated vaginal fluid and mucoadhesiveness were determined and compared. PC liposomes of various sizes, containing either chitosan or pectin were found to have higher entrapment efficiency of metronidazole than non-modified PC liposomes. The vesicle size was affected by the presence of mucoadhesive polymer on /in vesicles. Polymer-containing vesicles were larger and more prone to aggregation. Although we could not see difference in vesicle size or entrapment efficiency for vesicles containing chitosan of various molecular weights and DD, for pectin containing vesicles the effect of DM was observed. The stability of the different types of liposomes in simulated vaginal fluid mucoadhesiveness confirmed that polymer type affects vesicle properties. Optimization of chito an- and pectin-containing will be discussed.

5th International Symposium Phospholipids in Pharmaceutical Research, 2017

Knjiga sažetaka 4. kongresa farmaceuta Bosne i Hercegovine sa međunarodnim učešćem "Novi trendovi u farmaciji", 2019

Present study evaluated the applicability of stratum corneum mimicking PVPA barrier in determinin... more Present study evaluated the applicability of stratum corneum mimicking PVPA barrier in determining the drug penetration abilities of various types of liposomes: conventional liposomes (CL), deformable liposomes (DL) and propylene glycol liposomes (PGL). The skin-phospholipid vesicle-based permeation assay (PVPA) is a novel in vitro skin barrier model based on the tightly packed phospholipid vesicles mimicking structure and composition of stratum corneum. All of the liposomal formulations exhibited significantly higher permeabilities than the aqueous solution of hydrophilic drug, most probably due to the penetration-enhancing effect of the phospholipids. The highest Papp of DCS was attained with PGL-10-A, followed by DL-A, and the lowest values were obtained by CL-A. These results are consistent with the high elasticity of PGL-10-A and DL-A. The permeation of the hydrophilic drug from the liposomes was affected by their physicochemical properties, which were influenced by the lipid c...

Da bi se povecalo transdermalnu dopremu ljekovitih tvari, posljednjih se desetljeca velika pozorn... more Da bi se povecalo transdermalnu dopremu ljekovitih tvari, posljednjih se desetljeca velika pozornost posvecuje razvoju novih terapijskih sustava temeljenih na nanocesticama, kojima bi se nadvladali nedostaci postojecih klasicnih sustava. Među njima posebno mjesto zauzimaju lipidne vezikule koje svojim specificnim sastavom i svojstvima olaksavaju transport uklopljene ljekovite tvari. Ovim smo radom željeli pružiti osvrt na razlicite vrste lipidnih vezikula, od konvencionalnih (klasicnih) liposoma, preko elasticnih vezikula (deformabilnih liposoma) do etosoma, upoznati njihovu građu, specificnosti, interakcije s kožom te pružiti pregled provedenih istraživanja u (trans)dermalnoj primjeni.

67th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) in cooperation with the French Society of Pharmacognosy AFERP, 2019

Macedonian Pharmaceutical Bulletin

Phospholipid vesicles (liposomes) have been widely investigated as carriers for enhancing skin de... more Phospholipid vesicles (liposomes) have been widely investigated as carriers for enhancing skin delivery of drugs. The similarity between lipid compositions of liposomes with the skin structures enables liposomes to be used as physiologically acceptable drug delivery nanosystems. By manipulation of their physico-chemical properties the effective skin delivery of the encapsulated/incorporated drug can be achieved. They can be used as carriers to increase the solubility of the poorly soluble drugs or improve the stability of instable compounds. Phospholipid vesicles enable localized skin delivery of lipophilic drugs, enhance the penetration of hydrophilic drugs and help in reducing the drug irritation. Even without entrapped active compound, they have been shown to improve the skin condition by increasing the hydration level of the skin and integrity of the stratum corneum. The potentials and perspectives of different types of phospholipid vesicles have been summarized in this review, ...

Journal of Pharmaceutics and Drug Development, 2014

Capsaicin, an active ingredient of Capsicum fruit, is currently undergoing "revival" in the clini... more Capsaicin, an active ingredient of Capsicum fruit, is currently undergoing "revival" in the clinical management of pain. However, the choice of its formulation is rather limited to the use of "old-fashioned" tinctures and recently the patches. In an attempt to improve the therapeutic outcome and develop its skin-friendly formulation, we prepared the vesicle-based drug delivery system with capsaicin. Moreover, the use of standardized Capsicum extract, rather than a single active ingredient, is proposed to lead to simplified and more cost-effective formulations. Phospholipid-based vesicles, namely liposomes and ethosomes, were prepared with capsaicin, Capsicum tincture or Capsicum powder and characterized for particle size, entrapment efficiency and stability. The vesicular dispersions were incorporated in the hydrogels to increase the formulation stability, its retention time at the skin and overall acceptability. Both the standardized crude Capsicum powder and Capsicum tincture were successfully employed as sources of capsaicin which is, to the best of our knowledge, reported for the first time. The reported phospholipid-based delivery system for capsaicin could represent an improved topical treatment of arthritic pain.

Pharmaceutics

Biocompatible mucoadhesive formulations that enable a sustained drug delivery at the site of acti... more Biocompatible mucoadhesive formulations that enable a sustained drug delivery at the site of action, while exhibiting inherent antimicrobial activity, are of great importance for improved local therapy of vaginal infections. The aim of this research was to prepare and evaluate the potential of the several types of azithromycin (AZM)-liposomes (180–250 nm) incorporated into chitosan hydrogel (AZM-liposomal hydrogels) for the treatment of aerobic vaginitis. AZM-liposomal hydrogels were characterized for in vitro release, and rheological, texture, and mucoadhesive properties under conditions simulating the vaginal site of application. The role of chitosan as a hydrogel-forming polymer with intrinsic antimicrobial properties was explored against several bacterial strains typical for aerobic vaginitis as well as its potential effect on the anti-staphylococcal activity of AZM-liposomes. Chitosan hydrogel prolonged the release of the liposomal drug and exhibited inherent antimicrobial acti...

Conventional soy lecithin liposomes, deformable liposomes as well as PG-liposomes containing 10-3... more Conventional soy lecithin liposomes, deformable liposomes as well as PG-liposomes containing 10-30% of propylene glycol were prepared and compared with each other for the physicochemical properties. The characterization of the liposomes was based on balancing the size, the polidispersity, the zeta potential and the entrapment of diclofenac sodium. Regarding the size, PG-liposomes had significantly bigger mean diameter relative to conventional and deformable liposomes, proportionally to the propylene glycol content. Conventional and deformable liposomes were of similar zeta potential, while PG-liposomes showed slightly more negative zeta potential values. The highest entrapment of diclofenac sodium was achieved by PG-liposomes containing 30% of propylene glycol. In addition, all of the investigated various types of liposomes were prepared at two different phospholipid concentrations, whereat formulations with higher phospholipid content showed increased entrapment efficiency. Conside...

The objective of this study was development and in vitro evaluation of liposomes for the topical ... more The objective of this study was development and in vitro evaluation of liposomes for the topical treatment of chronic skin infections. Various types of liposomes differing in lipid composition and surface properties were prepared and examined for physical characteristics, in vitro drug release and antimicrobial activity. Soy phosphatidylcholine (SPC) liposomes and dipalmitoylphosphatidylcholine (DPPC)/dioctadecyldimethylammonium bromide (DODAB) liposomes encapsulating azithromycin were prepared by conventional film hydration method, followed by extrusion (SPC liposomes) or probe sonication (DPPC/DODAB liposomes). Anionic SPC liposomes were additionally coated with 0.3% (w/v) low Mw chitosan. Mean diameters, polydispersity index and zeta potentials of different phospholipid vesicles were determined by photon correlation spectroscopy. In vitro release studies were performed by Franz diffusion-cell method at 32 C using buffer pH 7.5 as receptor medium [1]. Antimicrobial activity of de...