Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of ß-Cyclodextrin-oligolactide Derivatives.

Enrofloxacin (ENR), a member of the fluoroquinolone class of antibiotics, is widely used in veterinary medicine to treat bacterial infections. Like many antibiotics, ENR has limited water solubility and low bioavailability. To address these challenges, drug formulations using solid dispersions, nanosuspensions, surfactants, cocrystal/salt formation, and inclusion complexes with cyclodextrins may be employed. The approach described herein proposes the development of ENR formulations by co-electrospinning ENR with custom-prepared cyclodextrin-oligolactide (CDLA) derivatives. This method benefits from the high solubility of these derivatives, enabling polymer-free electrospinning. The electrospinning parameters were optimized to incorporate significant amounts of ENR into the CDLA nanofibrous webs, reaching up to 15.6% by weight. The obtained formulations were characterized by FTIR and NMR spectroscopy methods and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study indicates that the presence of CDLA derivative does not inhibit the antibacterial activity of ENR, recommending these formulations for further development.

Poly(ethylene glycol) Methyl Ether Acrylate-Grafted Chitosan-Based Micro- and Nanoparticles as a Drug Delivery System for Antibiotics.

Nanotechnology is the science of creating materials at the nanoscale by using various devices, structures, and systems that are often inspired by nature. Micro- and nanoparticles (MPs, NPs) are examples of such materials that have unique properties and can be used as carriers for delivering drugs for different biomedical applications. Chitosan (CS) is a natural polysaccharide that has been widely studied, but it has a problem with low water solubility at neutral or basic pH, which limits its processability. The goal of this work was to use a chemically modified CS with poly(ethylene glycol) methyl ether acrylate (PEGA) to prepare CS micronic and submicronic particles (MPs/NPs) that can deliver different types of antibiotics, respectively, levofloxacin (LEV) and Ciprofloxacin (CIP). The particle preparation procedure employed a double crosslinking method, ionic followed by a covalent, in a water/oil emulsion. The studied process parameters were the precursor concentration, stirring speeds, and amount of ionic crosslinking agent. MPs/NPs were characterized by FT-IR, SEM, light scattering granulometry, and Zeta potential. MPs/NPs were also tested for their water uptake capacity in acidic and neutral pH conditions, and the results showed that they had a pH-dependent behavior. The MPs/NPs were then used to encapsulate two separate drugs, LEV and CIP, and they showed excellent drug loading and release capacity. The MPs/NPs were also found to be safe for cells and blood, which demonstrated their potential as suitable drug delivery systems for biomedical applications.

Lidocaine-Liposomes-A Promising Frontier for Transdermal Pain Management.

(1) Background: We aim to develop novel gel formulations for transdermal drug delivery systems in acute and inflammatory pain therapy. (2) Methods: We induced inflammation by the injection of λ-carrageenan on the hind paw of 80 Wistar male rats. The animals were randomized into eight groups of 10 rats each: C (placebo gel), E (EMLATM), L (lidocaine 2%), L-CD (lidocaine + cyclodextrin 2.5%), L-LP (lidocaine + liposomes 1.7%), L-CS (lidocaine + chitosan 4%), L-CSh (lidocaine + chitosan hydrochloride), and L-CS-LP (lidocaine + chitosan + liposomes). The behavior response was determined with a hot plate, cold plate, and algesimeter, each being performed at 30, 60, 120, 180, and 240 min after pain induction. At the end of the experiment, tissue samples were collected for histological assessment. (3) Results: L-LP had the greatest anesthetic effects, which was proven on the cold plate test compared to placebo and EMLATM (all p ≤ 0.001). L-CS-LP had a significant effect on cold plate evaluation compared to placebo (p ≤ 0.001) and on hot plate evaluation compared to EMLATM (p = 0.018). (4) Conclusions: L-LP is a new substance with a substantial analgesic effect demonstrated by the cold plate in the first 120 min. Further studies with more animals are needed to determine the maximum doses that can be applied for a better analgesia with minimum side effects.

Screen-printed interdigitated microelectrodes employment in dielectrophoretic manipulation of MWCNTs.

As key enablers of Industry 4.0 and Internet of Things, sensors are among the first devices which are to encounter fast physical transformation (from rigid to flexible) as of large-scale utilization of printing technologies. In order to step-up this process, adaptation of conventional fabrication technologies (based on metallization) employed in sensors' development should be tested and demonstrated. Within this paper, we are reporting the functionality of dielectrophoresis (DEP) for electromanipulation of multi-walled carbon nanotubes (MWCNTs) as sensing element, at the level of printed interdigitated electrodes. First, we present the flatbed screen-printed process of interdigitated microelectrodes on flexible substrate with tailored geometries employed afterwards for generating convenient dielectrophoretic forces of optimal magnitude and frequency for trapping MWCNTs. Successful dielectrophoresis operability of MWCNTs across silver-based screen-printed µIDE (interdigitated microelectrodes) provided with electrode gaps of ≈ 150 µm was validated and suitable values of the signal frequencies for avoiding parasitic electrokinetic phenomena (AC electro-osmosis, electrothermal effect) occurring simultaneously with DEP were identified. Time-dependent effect of DEP over MWCNTs bridges formation is discussed, as well as voltage magnitude contribution.

Polyurethane Degradable Hydrogels Based on Cyclodextrin-Oligocaprolactone Derivatives.

Polymer networks based on cyclodextrin and polyethylene glycol were prepared through polyaddition crosslinking using isophorone diisocyanate. The envisaged material properties are the hydrophilic character, specific to PEG and cyclodextrins, and the capacity to encapsulate guest molecules in the cyclodextrin cavity through physical interactions. The cyclodextrin was custom-modified with oligocaprolactone to endow the crosslinked material with a hydrolytically degradable character. SEM, DTG, and FTIR characterization methods have confirmed the morphology and structure of the prepared hydrogels. The influence of the crosslinking reaction feed was investigated through dynamic rheology. Further, thermal water swelling and hydrolytic degradation in basic conditions revealed the connectivity of the polymer network and the particular influence of the cyclodextrin amount in the crosslinking reaction feed on the material properties. Also, levofloxacin was employed as a model drug to investigate the drug loading and release capacity of the prepared hydrogels.

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy.

The aim of the present work was to obtain drug-loaded hydrogels based on combinations of dextran, chitosan/gelatin/xanthan, and poly (acrylamide) as a sustained and controlled release vehicle of Doxorubicin, a drug used in skin cancer therapy that is associated with severe side effects. Hydrogels for use as 3D hydrophilic networks with good manipulation characteristics were produced using methacrylated biopolymer derivatives and the methacrylate group's polymerization with synthetic monomers in the presence of a photo-initiator, under UV light stimulation (365 nm). Transformed infrared spectroscopy analysis (FT-IR) confirmed the hydrogels' network structure (natural-synthetic composition and photocrosslinking), while scanning electron microscopy (SEM) analysis confirmed the microporous morphology. The hydrogels are swellable in simulated biological fluids and the material's morphology regulates the swelling properties: the maximum swelling degree was obtained for dextran-chitosan-based hydrogels because of their higher porosity and pore distribution. The hydrogels are bioadhesive on a biological simulating membrane, and values for the force of detachment and work of adhesion are recommended for applications on skin tissue. The Doxorubicin was loaded into the hydrogels and the drug was released by diffusion for all the resulting hydrogels, with small contributions from the hydrogel networks' relaxation. Doxorubicin-loaded hydrogels are efficient on keratinocytes tumor cells, the sustained released drug interrupting the cells' division and inducing cell apoptosis; we recommend the obtained materials for the topical treatment of cutaneous squamous cell carcinoma.

Histological findings for the absorption of small and large liposomes - the basis of future drug delivery and contrast media systems.

BACKGROUND AND OBJECTIVES: The purpose of our study was to obtain and characterize carrier systems in different sizes that can affect oral absorption, since the mechanisms of liposome absorption are not yet fully understood. From stomach to the small intestine, liposomes can be gradually destroyed. Understanding the factors that affect oral absorption leads to developing safe and effective nanosystems to improve the oral delivery of therapeutics. MATERIALS AND METHODS: We determined the efficiency of the absorption of small and large liposomes at the level of gingival mucosa, heart, liver, testicles, kidneys, and lungs, using frozen-section fluorescence microscopy, on rat tissues after liposomes administration. A number of 36 male rats were divided in four groups: control groups, A and C, consisted of six rats each and did not receive liposomes; two other groups, B and D, were the experimental ones, and consisted of 12 male rats each. The animals received small liposomes (75-76 nm) and large liposomes (80-87 nm), respectively, administered either by endogastric tube or intraperitoneal injection. After 24 hours, the animals were sacrificed, and we harvested the organs. We performed frozen sections and analyzed them with fluorescence microscopy. RESULTS: The frozen sections obtained from all organs revealed a higher absorption level of small liposomes in the testicles, liver, and gum, while the large liposomes had a greater affinity for the liver, with variations dependent on the route of administration. CONCLUSIONS: Frozen-section fluorescence microscopy is a reliable technique for visualization of liposome absorption. Based on the size of these nanosystems, we revealed significant absorption for small liposomes in testicles, liver, heart, and gum, and for large liposomes mainly in the liver, compared with the control groups. The study advocates for the usage of liposomes for medical purposes, based on their absorption proprieties.

Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Particulate Hydrogels for Drug Delivery Applications.

Chitosan (CS) crosslinking has been thoroughly investigated, but the chemical reactions leading to submicronic hydrogel formulations pose problems due to various physical/chemical interactions that limit chitosan processability. The current study employs the chemical modification of chitosan by Michael addition of poly (ethylene glycol) methyl ether acrylate (PEGA) to the amine groups to further prepare chitosan particulate hydrogels (CPH). Thus, modified CS is subjected to a double crosslinking, ionic and covalent, in water/oil emulsion. The studied process parameters are polymer concentration, stirring speed, and quantity of ionic crosslinker. The CPH were structurally and morphologically characterized through infrared spectroscopy, scanning electron microscopy, light scattering granulometry, and zeta potential, showing that modified CS allows better control of dimensional properties and morphology as compared with neat CS. Swelling properties were studied in acidic and neutral pH conditions, showing that pH-dependent behavior was maintained after grafting and double crosslinking. The applicability of the prepared materials was further tested for drug loading and in vitro delivery of levofloxacin (LEV), showing excellent capacity. CPH were found to be cyto- and hemocompatible demonstrating their potential for effective use as a controlled release system for different biomedical applications.

The Influence of the Hydroxyl Type on Crosslinking Process in Cyclodextrin Based Polyurethane Networks.

The influence of the hydroxyl groups (OH) type on the polyaddition processes of isocyanates represents a critical approach for the design of multicomponent polyurethane systems. Herein, to prove the effect of hydroxyl nature on both the isocyanate-OH polyaddition reactions and the structure/properties of the resulting networks, two structurally different cyclodextrins in terms of the primary and secondary groups' ratio were analyzed, namely native ß-cyclodextrin (CD) and its derivative esterified to the primary hydroxyl groups with oligolactide chains (CDLA). Thus, polyurethane hydrogels were prepared via the polyaddition of CD or CDLA to isophorone diisocyanate polyethylene glycol-based prepolymers (PEG-(NCO)2). The degradable character of the materials was induced by intercalating oligolactide short sequences into the polymer chains composing the polymer network. In order to establish the influence of the OH type, the synthesis of polyurethane hydrogels was analyzed by a rheological investigation of the overall system reactivity. Materials properties such as swelling behavior, thermal properties and hydrolytic degradation were influenced by the reaction feed. Specifically, the presence of primary OH groups leads to more compact networks with similar water uptake, disregarding the CD content, while the predominance of secondary OH groups together with the presence of oligolactide spacers leads to the fine tuning of the water swelling properties.

Manifest/Non-Manifest Drug Release Patterns from Polysaccharide Based Hydrogels-Case Study on Cyclodextrin-κ Carrageenan Crosslinked Hydrogels.

The aim of this study is to offer a comprehensive view on drug release from hydrogel, from both an experimental and a theoretical point of view. Aiming to benefit cyclodextrins' properties (not irritant; stable; able to modify the physical, chemical and biological properties of active compounds; accessible at low prices) and those of carrageenan polysaccharide (antitumor, immunomodulatory, antihyperlipidemic, anticoagulant, biocompatibility, biodegradability), original hydrogel films based on beta cyclodextrin and kappa carrageenan using epichlorohydrin as crosslinking agent were prepared and characterized from morphological and physical/chemical points of view. The results (morphology, the swelling degree, and the loading/release capacity) proved their potential as carriers for different types of drugs. Further, a new theoretical model, from a multifractal paradigm of motion, was proposed for the drug release from hydrogel films, starting from the fundaments of its evolution at a microscopic level, and aiming to obtain information on system evolution, at both the spatial and temporal scales, inapproachable by quantitative measurements.

Hydrogels Based on Alginates and Carboxymethyl Cellulose with Modulated Drug Release-An Experimental and Theoretical Study.

New hydrogels films crosslinked with epichlorohydrin were prepared based on alginates and carboxymethyl cellulose with properties that recommend them as potential drug delivery systems (e.g., biocompatibility, low toxicity, non-immunogenicity, hemostatic activity and the ability to absorb large amounts of water). The characterization of their structural, morphological, swelling capacity, loading/release and drug efficiency traits proved that these new hydrogels are promising materials for controlled drug delivery systems. Further, a new theoretical model, in the framework of Scale Relativity Theory, was built with to offer insights on the release process at the microscopic level and to simplify the analysis of the release process.

Loading of Beclomethasone in Liposomes and Hyalurosomes Improved with Mucin as Effective Approach to Counteract the Oxidative Stress Generated by Cigarette Smoke Extract.

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomes modified with mucin to improve the ability of the payload to counteract the oxidative stress and involved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersing all components in the appropriate vehicle and sonicating them, thus avoiding the use of organic solvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed (polydispersity index lower than 0.22) and negatively charged (~-11 mV), were obtained. Moreover, these vesicle dispersions were stable for five months at room temperature (~25 °C). In vitro studies performed using the Next Generation Impactor confirmed the suitability of the formulations to be nebulized as they were capable of reaching the last stages of the impactor that mimic the deeper airways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibility studies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibility and safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes were capable of effectively counteracting the production of reactive oxygen species (ROS) induced by cigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce the damaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarette smoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer.

Entrapment of N-Hydroxyphthalimide Carbon Dots in Different Topical Gel Formulations: New Composites with Anticancer Activity.

In the present study, the antitumoral potential of three gel formulations loaded with carbon dots prepared from N-hydroxyphthalimide (CD-NHF) was examined and the influence of the gels on two types of skin melanoma cell lines and two types of breast cancer cell lines in 2D (cultured cells in normal plastic plates) and 3D (Matrigel) models was investigated. Antitumoral gels based on sodium alginate (AS), carboxymethyl cellulose (CMC), and the carbomer Ultrez 10 (CARB) loaded with CD-NHF were developed according to an adapted method reported by Hellerbach. Viscoelastic properties of CD-NHF-loaded gels were analyzed by rheological analysis. Also, for both CD-NHF and CD-NHF-loaded gels, the fluorescence properties were analyzed. Cell proliferation, apoptosis, and mitochondrial activity were analyzed according to basic methods used to evaluate modulatory activities of putative anticancer agents, which include reference cancer cell line culture assays in both classic 2D and 3D cultures. Using the rheological measurements, the mechanical properties of gel formulations were analyzed; all samples presented gel-like rheological characteristics. The presence of CD-NHF within the gels induces a slight decrease of the dynamic moduli, indicating a flexible gel structure. The fluorescence investigations showed that for the gel-loaded CD-NHF, the most intense emission peak was located at 370 nm (upon excitation at 330 nm). 3D cell cultures displayed visibly larger structure of tumor cells with less active phenotype appearance. The in vitro results for tested CD-NHF-loaded gel formulations revealed that the new composites are able to affect the number, size, and cellular organization of spheroids and impact individual tumor cell ability to proliferate and aggregate in spheroids.

Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab.

The aim of the present study is to obtain, for the first time, polymeric nanocarriers based on the chitosan grafted-poly(ethylene glycol) methacrylate derivative. The strategy involves the use of chitosan grafted-poly(ethylene glycol) methacrylate with high solubility in water, obtained via Michael addition, in order to prepare potentially non-toxic micro/nanoparticles (MNPs). By modifying chitosan, its solubility in aqueous media was improved. Micro/nanoparticles-based chitosan grafted-poly(ethylene glycol) methacrylate were obtained under mild condition, with good and controlled swelling properties in acetate buffer solution (ABS) and phosphate buffer solution (PBS). The technique selected for the preparation of the MNPs was a double crosslinking (ionic and covalent) process in reverse emulsion which provide the mechanical stability of the polymeric nanocarrier. The chitosan derivative and MNPs were thoroughly characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM). The Scanning Electron Microscopy photographs revealed that prepared MNPs have different diameters depending on the used stirring rate and polymer concentration. Nanoparticles potential as drug delivery system was analyzed by loading bevacizumab (BEV) a full-length monoclonal antibody. Also, the prepared particles were found suitable from the cytotoxicity and hemocompatibility point of view enabling their potential use as delivery system for the treatment of posterior segment of the eye conditions.

Polyglobalide-Based Porous Networks Containing Poly(ethylene glycol) Structures Prepared by Photoinitiated Thiol-Ene Coupling.

The high interest in polymers from natural resources prompted us to investigate the use of enzymatically synthesized polyglobalide (PGL) in the preparation of polymer networks with potential applications as biomaterials for drug delivery devices. Polymer networks were obtained under mild conditions by photoinitiated thiol-ene coupling between PGL and a poly(ethylene glycol- co-thiomalate) (PEG-SH) copolymer obtained by polycondensation. The obtained polymer networks were thoroughly characterized by Raman spectroscopy, scanning electron microscopy, titration of thiol groups and elemental analysis. Our study took into consideration the synthesis parameters for the polymer networks, such as the total polymer concentration and the SH/C=C functionality molar ratio. Swelling in both THF and water was assessed, and the potential of the materials for drug delivery was determined. The scanning electron microscopy images showed that the prepared polymer networks may have different morphologies ranging from homogeneous polymer materials to macroporous structures. Additionally, the prepared materials were found to be suitable from a cytotoxicity point of view, enabling their application as biomaterials for drug delivery devices.

Scaffolds Based on Collagen, Hyaluronan and Sericin with Potential Applications as Controlled Drug Delivery System.

Natural proteins have been extensively studied as matrices for tissue engineering, due to their excellent biocompatibility and biological properties associated with increasing cell proliferation. By generating complex materials, cell and tissue functions can be tailored to obtain a specific direction, according to the medical needs. The aim of this paper was to obtain scaffolds based on collagen, hyaluronan and sericin, with morphology and physical-chemical properties adequate for controlled drug delivery systems. In this aim various tests were performed: in vitro swelling and degradation studies, Fourier Transform Infrared spectroscopy (FT-IR), Scanning Electronic Microscopy (SEM) and thermogravimetric analysis. Loading and releasing of ibuprofen is also discussed. The results indicate that scaffolds based on collagen, hyaluronan and sericin have a porous structure, strength and stability adequate for skin tissue engineering. The obtained scaffolds swell, degrade and have controlled drug release properties in simulated biological fluids.

Rheological study of in-situ crosslinkable hydrogels based on hyaluronanic acid, collagen and sericin.

The elaboration of chemically crosslinked hydrogels based on collagen (C), hyaluronanic acid (HA) and sericin (S) with different polymer ratios was investigated by in-situ rheology. This reaction was performed via amide or ester bond reaction activated by carbodiimide, in pure water. Prior to molecule crosslinking, the rheological behaviour of the biopolymers (alone or in mixture) was characterized in a semi-dilute concentration regime. Both flow and dynamic measurements showed that uncrosslinked collagen alone appears to be rather elastic with yield stress properties, whereas uncrosslinked HA alone appears to be rather shear thinning and viscoelastic in agreement with entangled polymer behaviour. Sericin exhibited Newtonian low viscosity behaviour according to its very low molar mass. Before crosslinking, HA exhibited viscoelastic behaviour at concentrations above the critical entangled concentration (C*) in the mixtures, thus HA shows promise as a matrix for future crosslinked networks, whereas sericin did not significantly modify the rheology. During the reaction, followed by rheology, the kinetics were slower for pure HA systems compared with the mixtures (i.e., with added collagen and/or to a lesser extent sericin). At the same time, the final network of hydrogels (i.e., the elastic modulus) was more structured in the mixture based systems. This result is explained by ester bonds (the only possibility for pure HA systems), which are less favourable and reactive than amide bonds (possible with sericin and collagen). The presence of collagen in the HA matrix reinforced the hydrogel network. SEM studies confirmed the structure of the hydrogels, and in vitro degradability was globally consistent with the effect of the selected enzyme according to the hydrogel composition. All the elaborated hydrogels were non-cytotoxic in vitro.

New hybrid magnetic nanoparticles based on chitosan-maltose derivative for antitumor drug delivery.

The aim of the present study is to obtain, for the first time, polymer magnetic nanoparticles based on the chitosan-maltose derivative and magnetite. By chemically modifying the chitosan, its solubility in aqueous media was improved, which in turn facilitates the nanoparticles' preparation. Resulting polymers exhibit enhanced hydrophilia, which is an important factor in increasing the retention time of nanoparticles in the blood flow. The preparation of nanoparticles relied on the double crosslinking technique (ionic and covalent) in reverse emulsion which ensures the mechanical stability of the polymer carrier. The characterization of both the chitosan derivative and nanoparticles was accomplished by Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance Spectroscopy, Scanning Electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, Vibrating Sample Magnetometry, and Thermogravimetric Analysis. The evaluation of morphological, dimensional, structural, and magnetical properties, as well as thermal stability and swelling behavior of nanoparticles was made from the point of view of the polymer/magnetite ratio. The study of 5-Fluorouracil loading and release kinetics as well as evaluating the cytotoxicity and hemocompatibility of nanoparticles justify their adequate behavior in their potential use as devices for targeted transport of antitumor drugs.

Nanotechnology approaches for pain therapy through transdermal drug delivery.

The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

Modern drug delivery systems for targeting the posterior segment of the eye.

Some of the most dangerous diseases of the eye are related to the posterior segment. Diseases such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis and retinitis pigmentosa are difficult to treat using classical methods because of the many internal barriers of the eye which affect the drug efficiency. In this review, we will summarize the main research directions in the field of medicamentous treatment of posterior eye disorders belonging to the controlled drug delivery concept. The review is starting with the most important knowledge regarding anatomy and pathology of the posterior segment of the eye and is continuing with the current treatment methods of the eye posterior segment illnesses and drawbacks of these methods, the drugs administration pathways to the posterior segment of the eye. The last three sections present the state of the art regarding the latest discoveries including the commercial products in the modern drug delivery systems; the main classes of materials treated in the present review are implants, hydrogels and nano- microparticulate systems.