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Overuse of antimicrobials by the population has contributed to genetic modifications in bacteria and development of antimicrobial resistance, which is very difficult to combat nowadays. To solve this problem, it is necessary to develop new systems for the administration of antimicrobial active principles. Biocomposite systems containing silver nanoparticles can be a good medical alternative. In this context, the main objective of this study was to obtain a complex system in the form of a biocomposite film with antimicrobial properties based on chitosan, poly (vinyl alcohol) and silver nanoparticles. This new system was characterized from a structural and morphological point of view. The swelling degree, the mechanical properties and the efficiency of loading and release of an anti-inflammatory drug were also evaluated. The obtained biocomposite films are biocompatibles, this having been demonstrated by in vitro tests on HDFa cell lines, and have antimicrobial activity against S. aureus. The in vivo tests, carried out on rabbit subjects, highlighted the fact that signs of reduced fibrosis were specific to the C2P4.10.Ag1-IBF film sample, demonstrated by: intense expression of TNFAIP8 factors; as an anti-apoptotic marker, MHCII that favors immune cooperation among local cells; αSMA, which marks the presence of myofibroblasts involved in approaching the interepithelial spaces for epithelialization; and reduced expression of the Cox2 indicator of inflammation, Col I.

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core–shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure.

Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro. The obtained results showed that the optimal liposomal formulation is a crosslinked gel based on sodium alginate and hyaluronic acid containing AS1411-aptamer conjugated liposomes loaded with 5-fluorouracil, which appeared to have favorable biosafety effects and may be used as a new therapeutic approach for the topical treatment of basal cell carcinoma.

Cancer remains one of the world&rsquo, s most devastating diseases and is responsible for more than 20% of all deaths. It is defined as uncontrolled proliferation of cells and spreads rapidly to healthy tissue. Controlled drug delivery systems offers great opportunities for the development of new non-invasive strategies for the treatment of cancers. The main advantage of these systems is their capacity to accumulate in tumors via enhanced permeability and retention effects. In the present study, an innovative hybrid drug delivery system based on nanocapsules obtained from the interfacial condensation between chitosan and poly(N-vinyl pyrrolidone-alt-itaconic anhydride) and containing both magnetic nanoparticles and an antitumoral drug was developed in order to improve the efficiency of the antitumoral treatment. Using dynamic light scattering, it was observed that the mean diameter of these hybrid nanocapsules was in the range of 43 to 142 nm. SEM confirmed their nanometric size and their well-defined spherical shape. These nanocapsules allowed the encapsulation of an increased amount of 5-fluorouracil and provided controlled drug release. In vitro studies have revealed that these drug-loaded hybrid nanocapsules were able to induce a cytostatic effect on breast carcinoma MCF-7 cell lines (Human Caucasian breast adenocarcinoma - HTB-22) comparable to that of the free drug.

New topical gel formulations based on sodium alginate and hyaluronic acid containing AS1411 aptamer-functionalized polymeric nanocapsules loaded with an antitumoral drug (5-Fluorouracil) were designed as an innovative approach for the skin cancer treatment. Several important analyses were used to characterize these obtained topical gel formulations, namely: rheological tests, permeation assays across Strat-M® artificial membrane, ex-vivo permeation assays across chicken skin membrane, haemolysis tests, skin irritation tests, in vitro cytotoxicity assay on human basal carcinoma cells and in vivo tests. Rheological tests revealed that apparent viscosity decreases with the increase of the shear rate, for analyzed samples, which demonstrates a shear thinning behavior. Low levels of hemolysis values which ranged between 0.03 and 0.55% suggested that the tested formulations did not induce red blood cell lysis.. The gel formulations containing nanocapsules loaded with 5-FU proved to be non-irritant. Furthermore, by study the ex-vivo diffusion properties across the chicken skin membrane, it was proved that nanoencapsulation enhance the permeability properties of 5-FU. In vitro cytotoxicity assay on TE 354.T (ATCC® CRL-7762™) human basal carcinoma cell line showed that the obtained formulations loaded with 5-Fluorouracil manifest an important cytotoxic effect. Finally, the presence of Langerhans CD68 cells-positive in the epidermis and epithelial sheath of dermal hair follicles suggests a specific activation, migration and retrieval of nanoparticles by these cells. Following the results obtained in this study we can appreciate that the obtained topical gel formulations have a favourable biosafety and good antitumor effects which makes them attractive for skin cancer treatment.

Non-aqueous dispersions (NAD) with two types of polymeric nanoparticles (NPs), such as hydrophobic poly(&epsilon, caprolactone) (PCL) and hydrophilic cross-linked poly(vinylpyrrolidone) (PNVP), were synthesized in the present study starting from monomer-in-silicone oil (PDMS) polymerizable non-aqueous emulsions stabilized with the same tailor-made PDMS-based block copolymer. These NPs were loaded with CCisplatin, an antitumoral model drug, directly from the emulsion polymerization step, and it was observed that the presence of the drug leads only to a slight increase of the NPs size, from 120 to 150 nm. The drug release kinetics was evaluated at 37 &deg, C in phosphate buffer at pH = 7.4 and it appeared that the drug release rate from the hydrophilic cross-linked PNVP-based NPs is higher than that from the hydrophobic PCL-based NPs. Moreover, haemolysis tests revealed the fact that these two types of NPs have a good compatibility with the blood. Furthermore, for both the free and drug-loaded NPs, the in vitro cytotoxicity and apoptosis was studied on two types of cancer cell lines, such as MCF-7 (breast cancer cell line) and A-375 (skin cancer cell line). Both types of NPs had no cytotoxic effect but, at a concentration of 500 &mu, g/mL, presented an apoptotic effect similar to that of the free drug.

More than one out of every three new cancers is a skin cancer, and the large majority are basal cell carcinomas (BCC). Targeted therapy targets the cancer&rsquo, s specific genes, proteins, or tissue environment that contributes to cancer growth and survival and blocks the growth as well as the spread of cancer cells while limiting damage to healthy cells. Therefore, in the present study AS1411 aptamer-functionalized liposomes for the treatment of BCC were obtained and characterized. Aptamer conjugation increased liposome size, suggesting that the presence of an additional hydrophilic molecule on the liposomal surface increased the hydrodynamic diameter. As expected, the negatively charged DNA aptamer reduced the surface potential of the liposomes. Vertical Franz diffusion cells with artificial membranes were used to evaluate the in vitro release of 5-fluorouracil (5-FU). The aptamer moieties increase the stability of the liposomes and act as a supplementary steric barrier leading to a lower cumulative amount of the released 5-FU. The in vitro cell viability, targeting capability and apoptotic effects of liposomes on the human dermal fibroblasts and on the basal cell carcinoma TE 354.T cell lines were also evaluated. The results indicate that the functionalized liposomes are more efficient as nanocarriers than the non-functionalized ones.

In this chapter, some of the most important materials based on polysaccharides will be discussed with a perspective on the challenges, advantages, and disadvantages of their applications as injectable drug delivery systems. Utilization of polysaccharides as biomaterials has greatly impacted the advancement of modern medicine. Polysaccharides exhibit a huge structural and chemical diversity, and due to their biochemical similarity with human extracellular matrix components are readily recognized and accepted by the body. On the one hand, their mucoadhesion, which provides neutral coatings with low surface energy, prevents the nonspecific protein adsorption. On the other hand, the high number of hydroxyl groups in the polysaccharide backbone allows the incorporation of different specific ligands in order to obtain functionalized colloidal systems. Polysaccharide-based nanoparticles have received considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique characteristics. The attractiveness of these systems for medical purposes is based on their important and unique features, such as their much higher surface to mass ratio, their quantum properties, and their ability to absorb or to encapsulate high quantities of active principles. Chitosan, alginate, hyaluronic acid, dextran, guar gum, pectin, and cellulose are the most commonly used polysaccharides in the preparation of different types of injectable drug delivery systems. An overview on the physicochemical characteristics of such delivery systems will be carried out for each polysaccharide.

Polysaccharides are carbohydrate polymers comprising multiple saccharide units linked through glycosidic bonds. Most polysaccharides are easily and inexpensively recovered natural-based products with a wide variety of biochemical and biomechanical functions. Drug delivery systems based on these biodegradable and biocompatible polysaccharides can assure a long retention time and thus a prolonged effect of the active principle in the oral cavity due to their mucoadhesive properties. After a short description of the structure, function, and biochemistry of the oral cavity, the principal types of orodental region diseases will be presented in this chapter. The next paragraph will be dedicated to the discussion of the preparation methods and physicochemical characteristics of different polysaccharide-based delivery systems addressed to the oral cavity. The existing orodental polysaccharide drug delivery systems based on commonly used chitosan, cellulose, dextran, and other polysaccharides will be explored in detail in order to understand the influence of different parameters, such as saliva, site of administration, etc., on the stability of these colloidal systems. Also, the type of the formulations (mouthwashes, dental varnishes, oral sprays, etc.), which are expected to provide physical protection for the incorporated drug-loaded polysaccharide materials, will be overviewed.