Controlled Drug Delivery Systems Research Articles

Recent Advances in Mesoporous Silica Nanoparticles for Targeted Drug Delivery Applications.

Nanotechnology provides the means to design and fabricate delivery vehicles capable of overcoming physiologically imposed obstacles and undesirable side effects of systemic drug delivery. This protocol allows maximal targeting effectiveness and therefore enhances therapeutic efficiency. In recent years, Mesoporous Silica Nanoparticles (MSNPs) have sparked interest in nanomedicine research community, particularly for their promising applications in cancer treatment. The intrinsic physio-chemical stability, facile functionalization, high surface area, low toxicity, and great loading capacity for a wide range of chemotherapeutic agents make MSNPs very appealing candidates for controllable drug delivery systems. Importantly, the peculiar nanostructures of MSNPs enabled them to serve as an effective drug, gene, protein and antigen delivery vehicle for a variety of therapeutic regimens. For these reasons, in this review article, we underscore the recent progress in the design and synthesis of MSNPs along with the parameters influencing their characteristic features and activities. In addition, the process of absorption, dissemination and secretion by injection or oral management of MSNPs are also discussed, as they are key directions for potential utilization of MSNPs. Factors influencing the in vivo fate of MSNPs will also be highlighted, with a main focus on particle size, morphology, porosity, surface functionality and oxidation. Given that combining other functional materials with MSNPs may increase their biological compatibility, monitor drug discharge, or improve absorption by tumor cells coated MSNPs; these aspects are also covered and discussed herein.

Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration

The inappropriate regenerated fibrous cartilage and subchondral bone of the injured chondral defect ultimately cause degeneration of the regenerated cartilage, which eventually leads to the failure of cartilage repair. In this study, we developed a macrophage-modulated and injectable ‘building block’ drug delivery system comprised of porous chitosan (CS) microspheres and hydroxypropyl chitin (HPCH) hydrogel, where the dimethyloxallyl glycine (DMOG) was encapsulated in the thermosensitive HPCH hydrogel (HD) while kartogenin (KGN) was conjugated on the porous CS microspheres (CSK-PMS). The developed HD/CSK-PMS composite scaffold effectively modulated the microenvironment at the defect site, achieved local macrophage M2 polarization and promoted cartilage regeneration. The fast-degradable HD favored hyaline cartilage regeneration, while the highly stable CSK-PMS supported the endochondral ossification and regenerated the subchondral bone. In vitro and in vivo evaluations revealed that the newly developed HD/CSK-PMS as a controlled drug delivery system could effectively create M2 macrophage microenvironment and orchestrate osteochondral (OC) regeneration. These findings indicate the importance of the immune microenvironment and subchondral bone for high-quality cartilage repair, and thus the immunomodulation-based hydrogel/PMS composite system could be a promising candidate for OC regeneration.

Design and Evaluation of Mebeverine Hydrochloride Microspheres with Novel Timed Release Polymers

Drugs having the shorter half life are needed to be administered frequently in order to maintain the required therapeutic concentrations. One of the strategies to overcome the frequent administration is by developing the controlled release formulations. Microspheres including the micro particles and microcapsules (having a core of the drug) of 1-1000 μm in diameter are one of the emerging controlled drug delivery systems that can eliminate the frequent drug administration. Hence, in the present study an effort was made to formulate microsphere of Mebeverine HCl by using different delayed-released polymers at different concentrations. Different formulations were prepared using guar gum and glutaraldehyde as delayed release polymers and evaluated for the properties like the effect of polymer concentrations on the microsphere formation, particle size, muco-adhesion etc. Also, the prepared microspheres were evaluated for flow properties along with the drug release rates. From the results, it was observed that higher concentrations of polymer resulted in better microsphere formation compared to low concentrations. Projection Microscopic images of optimized formulation showed that the microspheres have rough surface. In vitro drug release studies showed that the optimized formulation showed 96.26 percent Mebeverine HCl release at the end of 13 hours. Overall, it can be concluded that the preparation of Mebeverine HCl microspheres can eliminate the need for frequent administration thereby providing the better therapeutic compliance compared to the conventional dosage forms.

PH Responsive Polyurethane for the Advancement of Biomedical and Drug Delivery.

Due to the specific physiological pH throughout the human body, pH-responsive polymers have been considered for aiding drug delivery systems. Depending on the surrounding pH conditions, the polymers can undergo swelling or contraction behaviors, and a degradation mechanism can release incorporated substances. Additionally, polyurethane, a highly versatile polymer, has been reported for its biocompatibility properties, in which it demonstrates good biological response and sustainability in biomedical applications. In this review, we focus on summarizing the applications of pH-responsive polyurethane in the biomedical and drug delivery fields in recent years. In recent studies, there have been great developments in pH-responsive polyurethanes used as controlled drug delivery systems for oral administration, intravaginal administration, and targeted drug delivery systems for chemotherapy treatment. Other applications such as surface biomaterials, sensors, and optical imaging probes are also discussed in this review.

Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems-State of Knowledge and Future Prospects.

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.

FORMULATION AND CHARACTERIZATION OF ACECLOFENAC LOADED STARCH MICROSPHERE

Microspheres are a new category of novel drug delivery system which targets to increase the bioavailability and is formulated expediently to obtain prolonged or controlled drug delivery system in the body. Aceclofenac; a non steroidal anti inflammatory drug, is used to treat hurting rheumatic conditions such as osteoarthritis, rheumatoid arthritis and alkylosing spondylitis. It eases pain and reduces inflammation at various sites. Aceclofenac acts by blocking the effect of chemical mediators called cyclo-oxygenase (COX) enzymes which are released at inflamed regions. The aim of this research was to formulate Aceclofenac loaded starch microspheres and evaluate its in vitro properties to enhance the bioavailability of aceclofenac tablet. Aceclofenac loaded starch microspheres were prepared using emulsion cross linking method. Aceclofenac microspheres loaded with starch polymer were characterized, evaluated and it was found to influence all the parameters. The microspheres prepared showed great entrapment efficiency. In vitro release of all prepared polymeric formulations was quite good.

The effect of PEO homopolymers on the behaviours and structural evolution of Pluronic F127 smart hydrogels for controlled drug delivery systems

Understanding the structure-property relationships of drug delivery system (DDS) components is critical for their development and the prediction of bodily performance. This study investigates the effects of introducing polyethylene oxide (PEO) homopolymers, over a wide range of molecular weights, into Pluronic injectable smart hydrogel formulations. These smart DDSs promise to enhance patient compliance, reduce adverse effects and dosing frequency. Pharmaceutically, Pluronic systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and ease of injectability as solutions before transforming into gel matrices at body temperature. This paper presents a systematic and comprehensive evaluation of gelation and the interplay of microscopic and macroscopic properties under both equilibrium and non-equilibrium conditions in controlled environments, as measured by rheology in conjunction with time-resolved Small Angle Neutron Scattering (SANS). The non-equilibrium conditions investigated in this work offer a better understanding of the two polymeric systems’ complex interactions affecting the matrix thermo-rheological behaviour and structure and therefore the future release of an active pharmaceutical ingredient from the injectable DDS.

PCL-coated magnetic Fe3O4 nanoparticles: Production, characterization and viability on stem cells

Magnetic therapies, such as controlled drug delivery systems and hyperthermia, are promising approaches for conventional cancer treatment. The aim of the present study has been to synthesize Fe3O4 nanoparticles (NP) coated with different poly(caprolactone) (PCL) concentrations through a simple and inexpensive method. X-ray diffractometry (XRD) transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the produced particles. Surface modification was confirmed through Fourier-transform infrared spectroscopy (FTIR), and vibrating sample magnetometry (VSM) showed the magnetic character of the samples. The synthesized materials were composed mainly of spherical superparamagnetic magnetite, with sizes between 9 and 11 nm. Samples with higher polymer loading presented smaller hydrodynamic sizes, proving that the polymer improves the biostability of the nanoparticles. Magnetization values also varied with surface modification, but even in the highest dosage, these values were not compromised. The cytotoxicity of the NPs was examined by MTT and FDA/PI assays, demonstrating the non-toxic character of the produced particles in the studied concentrations. The obtained nanoparticles showed significant superparamagnetic behavior, even in the presence of PCL. This phenomenon could allow for their application as a further optimized vector in hyperthermia cancer treatment, controlled drug delivery and resonance imaging.

Lignin-Based Porous Biomaterials for Medical and Pharmaceutical Applications.

Over the past decade, lignin-based porous biomaterials have been found to have strong potential applications in the areas of drug delivery, tissue engineering, wound dressing, pharmaceutical excipients, biosensors, and medical devices. Lignin-based porous biomaterials have the addition of lignin obtained from lignocellulosic biomass. Lignin as an aromatic compound is likely to modify the materials’ mechanical properties, thermal properties, antioxidant, antibacterial property, biodegradability, and biocompatibility. The size, shape, and distribution of pores can determine the materials’ porous structure, porosity, surface areas, permeability, porosity, water solubility, and adsorption ability. These features could be suitable for medical applications, especially controlled drug delivery systems, wound dressing, and tissue engineering. In this review, we provide an overview of the current status and future potential of lignin-based porous materials for medical and pharmaceutical uses, focusing on material types, key properties, approaches and techniques of modification and fabrication, and promising medical applications.

SYNTHESIS CO(BENZENESULFONAMIDE SERINOL-LACTIDE) FOR PREPARATION OF THE PH-SENSITIVE HYDROGEL

The pH-sensitive hydrogel based on polyurethanes is one of the most popular biodegradable copolymers that have been used in drug carrier applications. Polyurethanes containing sulfonamide groups exhibit sensitivity to changes in pH environment because they can receive and donate cationic hydrogens. In this research, the co(benzenesulfonamide serinol-lactide), named Co(BSSe-LA), was synthesized based on the ring-opening reaction of lactide and hydroxyl groups of benzenesulfonamide serinol (BSSe). The influence of reaction time and content (wt.%) of stannous octoate catalyst on the reaction efficiency of Co(BSSe-LA) was investigated. Proton nuclear magnetic resonance (H1NMR) and Fourier transform infrared spectroscopy (FTIR) analyses confirmed the successful formation of BSSe and Co(BSSe-LA). Besides, the results show that the reaction efficiency of Co(BSSe-LA) increased when the reaction time and the stannous octoate concentration increased. The reaction efficiency of Co(BSSe-LA) was 33.67 % with reaction parameters including catalyst content of 1.2 wt.%, reaction time of 24 hours and BSSe/LA molar ratio of 1/2. Co(BSSe-LA) was prepared for polymerization of polyurethane and fabrication of pH-sensitive hydrogel. Furthermore, the product can be decomposed easily in aqueous medium thanks to the ester group of lactide. This hydrogel copolymer may be potential as an injectable hydrogel for the controllable drug and protein delivery system.

Development and pharmacokinetic evaluation of osmotically controlled drug delivery system of Valganciclovir HCl for potential application in the treatment of CMV retinitis.

Valganciclovir HCl (VGH) is the widely used drug for the treatment of cytomegalovirus (CMV) retinitis infection with an induction dose of 900mg per oral (p.o.) twice a day and a maintenance dose of 900mg (p.o.). This required dose of the drug also leads to multiple side effects due to repeated administration. The research was highlighted to develop, formulate, optimize, and evaluate single-core osmotic pump (SCOP) tablet of VGH with the dose of 450mg to reduce dosing frequency and associated side effects. The decrease in dose also minimizes the hepatic and nephrotic load. The optimized batch of the formulation was subjected to comparative in vitro and in vivo evaluation. The tablet core composition is the primary influencer of the drug delivery fraction in a zero order, whereas the membrane characteristics control the drug release rate. In vivo pharmacokinetic studies revealed that the newly developed osmotic formulation has controlled zero-order release for 24h with a single dose of 450mg while the marketed formulation requires twice administration within 24h to maintain the plasma concentration in the therapeutic window. The pharmacokinetic study demonstrated that the developed formulation has the area under curve (AUC) of 58.415µgh/ml with single dose while the marketed formulation shows the AUC of about 37.903µgh/ml and 31.983µgh/ml for first and second dose, respectively. The large AUC demonstrates the extended release of drug with a single dose and effective plasma concentration. Hence, the developed formulation can be a promising option for the treatment of CMV retinitis with the minimum dose and dosing frequency.

An Overview of Pharmaceutical Mini Tablet

The objective of controlled drug delivery systems is to decrease the frequency of dosing and to increase the efficiency of the drug by localization. In oral controlled drug delivery systems, Mini-tablets represent the new trend in Solid oral dosage forms are most acceptable dosage forms especially tablets are most widely accepted by people of different age groups. Mini tablets with a diameter alike to or smaller than 3–6 mm. mini tablets are multiple unit dosage forms and are convenient to pellets or any other oral dosage forms as there calm to manufacture and stability snags are less. Some types of mini tablets are like to Oral disintegrating mini tablets, pH responsive mini tablets, Biphasic mini tablets, gastro retentive mini tablets, paediatric mini tablets, and bio adhesive mini tablets.

Insoluble Salt of Memantine with a Unique Fluorescence Phenomenon.

Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. In this study, reactions of memantine (Mem) with pamoic acid (Pam) were carried out to form insoluble salts (Mem-Pam). Four polymorphic forms (Forms I-IV) of Mem-Pam were successfully obtained through polymorphic screening, which were systematically characterized by X-ray powder diffraction (PXRD), thermal analysis (TGA and DSC), single-crystal X-ray diffraction (SXRD), and solid-state fluorescence. Compared with the hydrochloride form, the dissolution and release rates of these four forms are lower. The presence of pamoic acid reduces the release rate of memantine and makes it possible to achieve a sustained release of the drug. Interestingly, because of the presence of memantine, each polymorphic solid crystal of Mem-Pam has unique fluorescence emission. Therefore, memantine and pamoic acid have a synergistic effect on the fluorescence performance and can be expected to be used for real-time monitoring in continuous and controlled release drug delivery systems. In addition, the polymorphic solid crystals also exhibit reversible mechanochromic luminescence under the fumigation of acetonitrile vapor, which has a guiding role in the fluorescence design and synthesis of Pam substances and is expected to be used for information security, visual inspection of organic substances, etc.

Drug Carriers

In recent years, there has been an exponential interest in the development of novel drug delivery systems using drug carriers. Drug carriers offer significant advantages over the conventional drug delivery systems in terms of high stability, high specificity, high drug loading capacity, controlled release of drug and ability to deliver both hydrophilic and hydrophobic drugs. As a result of their unique behaviors, drug carriers have a wide range of biomedical and industrial applications. Nanospheres are associated with a lot of benefits such as ease of administration to target sites, reduction in toxicity level and ease of passage via the capillary vessels. Hydrogel nanoparticles are useful in the treatment of inflammatory diseases, as bioresponsive hydrogels in drug delivery system and as a carrier in controlled drug delivery system. Carbon nanotubes have a large surface area which has the ability to adsorb or conjugate with a wide variety of therapeutic and diagnostic agents. They are useful in the areas of gene delivery, tissue regeneration and biosensor diagnosis. Liposomes are known to target a drug to a specific site. They entrap drugs which are released for subsequent absorption. They are used to achieve active targeting, increase efficacy and therapeutic index of drugs. Niosomes improve the solubility and oral bioavailability of poorly soluble drugs. They protect drugs from biological environment, increase the stability of entrapped drugs and they can easily reach the site of action. Aquasomes are nanoparticulate carriers that can be characterized for structural analysis. They preserve conformational integrity and biochemical stability of drugs. Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and the systemic circulation. They contain phospholipids which could be in form of phosphatidyl choline (PC), hydrogenated PC, phosphatidic acid (PA), Phosphatidyl serine (PS) and phosphatidyl inositol (PI). Ethosomes are known to increase skin permeation of drugs, improve biological activity and pharmacodynamics profile of drugs. This review aims to emphasize the importance of drug carriers in drug delivery system, and applications of drug carriers in various areas of research, technology and treatment.

Formulation and Evaluation of Interpenetrating Polymer Network Microparticles of Diclofenac Sodium

Diclofenac sodium, a model anti-inflammatory drug, has adverse effects like gastric irritation and hepatic toxicity. To overcome these problems Interpenetrating Polymer Network microparticles can be used as a controlled drug delivery system. Preparation of Interpenetrating Polymer Network microparticles using two or more polymer is a novel approach as the polymers produce synergistic effect which could increase the mechanical strength and resilience of the microparticles. The aim of the study was to prepare Interpenetrating Polymer Network microparticles of Diclofenac Sodium using chitosan and Ghatti gum which were used to deliver Diclofenac Sodium to the intestine. Microparticles prepared by emulsion-cross-linking method using gluteraldehyde as a cross-linker were characterized by Fourier Transform Infrared Spectroscopy, Differential scanning calorimetry, Scanning electron microscopy and evaluated for in vitro dissolution rate. Fourier Transform Infrared Spectroscopy studies confirmed the absence of chemical interactions between drug, polymers and cross-linking agent. Differential scanning calorimetric results indicated amorphous dispersion of Diclofenac Sodium into Interpenetrating Polymer Network matrix. Scanning electron microscopy pictures showed that microparticles did not agglomerate and had a rough surface. Hydrated surface after swelling showed spongy porous surface which indicated the mechanism of drug release as diffusion. Particle size ranged between 294 to 366 µm. DS percentage encapsulation efficiency ranged from 84.09 to 96.81%. In vitro release studies indicated a dependence of drug release rates on both the amount of CS and GG used in preparation of microparticles. The release was extended up to 12 h and release rates indicated a non-Fickian and super case II mechanism.

Minoxidil-loaded hyaluronic acid dissolving microneedles to alleviate hair loss in an alopecia animal model

Alopecia is defined as hair loss in a part of the head due to various causes, such as drugs, stress and autoimmune disorders. Various therapeutic agents have been suggested depending on the cause of the condition and patient sex, and age. Minoxidil (MXD) is commonly used topically to treat alopecia, but its low absorption rate limits widespread use. To overcome the low absorption, we suggest microneedles (MNs) as controlled drug delivery systems that release MXD. We used hyaluronic acid (HA) to construct MN, as it is biocompatible and safe. We examined the effect of HA on the hair dermal papilla (HDP) cells that control the development of hair follicles. HA enhanced proliferation, migration, and aggregation of HDP cell by increasing cell-cell adhesion and decreasing cell substratum. These effects were mediated by the cluster of differentiation (CD)-44 and phosphorylation of serine‑threonine kinase (Akt). In chemotherapy-induced alopecia mice, topical application of HA tended to decrease chemotherapy-induced hair loss. Although the amount of MXD administered by HA-MNs was 10% of topical treatment, the MXD-containing HA-MNs (MXD-HA-MNs) showed better effects on the growth of hair than topical application of MXD. In summary, our results demonstrated that HA reduces hair loss in alopecia mice, and that delivery of MXD and HA using MXD-HA-MNs maximizes therapeutic effects and minimize the side effects of MXD for the treatment of alopecia. Statement of significance(1) Significance, This work reports a new approach for treatment of alopecia using a dissolving microneedle (MN) prepared with hyaluronic acid (HA). The HA provided a better environment for cellular functions in the hair dermal papilla cells. The HA-MNs containing minoxidil (MXD) exhibited a significant reduction of hair loss, although amount of MXD contained in them was only 10% of topically applied MXD., (2) Scientific impact, This is the first report demonstrating the direct anti-alopecia effects of HA administrated in a transdermal route and the feasibility of novel therapeutics using MXD-containing HA-MNs. We believe that our work will excite interdisciplinary readers of Acta Biomaterialia, those who are interested in the natural polymers, drug delivery, and alopecia.

Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery

Nanostructured lipid carriers (NLC) are novel lipidic nanosystems that provide significant improvements in terms of high drug loading capacity and controlled drug release. The purpose of the present work was based on the design, development, and physicochemical characterization of lactoferrin-loaded NLCs as a new therapeutic alternative for the keratoconus treatment. Lactoferrin-loaded NLCs were successfully prepared by a double emulsion/solvent evaporation method. The resultant NLC were assessed in terms of particle size, size distribution, surface charge, morphology, encapsulation efficiency (EE), loading capacity (LC), stability, cytotoxicity, in vitro release, and ocular surface retention. Resulting data showed a size of 119.45 ± 11.44 nm, a 0.151 ± 0.045 PDI value and a surface charge of −17.50 ± 2.53 mV. Besides, high EE and LC values were obtained (up to 75%). The in vitro release study demonstrated a lactoferrin controlled release pattern. NLCs were also stable, non-toxic and show mucoadhesive properties. Thus, a consistent preclinical base was obtained, where NLC may be considered as a potential controlled release novel drug delivery system of lactoferrin for the keratoconus treatment.

Effect of Stirring Speed on the Formation and Characteristic of Alginate Microspheres via Gelation/ Emulsification Method

Alginate microspheres are used for controlled drug delivery system; however, the formation and size control of alginate microspheres is necessary for these systems to be effective. Therefore, the influence of stirring speed on the characteristic of alginate microspheres (AMs) via emulsification/gelation method was evaluated. Alginate solution was emulsified into liquid paraffin oil to form water in oil emulsion and followed by cross-linked with Ca2+ ions. The shape and surface characteristics of AMs were determined by scanning electron microscope (SEM). Morphological observation shows that at lower stirring speed, the alginate particles were irregularly shaped with a rough surface. Whereas, increasing stirring speed resulted in spherical microspheres with smoother surface. Particle size analysis by laser diffraction method showed a decreased in mean particle size and more homogeneous distribution as the stirring speed increased. The mean particle size of AMs was found to be in the range of 28.5-69.6 μm. Fourier transform infrared (FTIR) analysis shows that there was no shifting in peak positions in the transmittance spectrum of AMs. This study suggested that the formation of AMs can be synthesis via emulsification/gelation method and the size of the AMs can be tailor by varying the stirring speed.

Development and Characterization of Cephradine Proniosomes for Oral Controlled Drug Delivery

Abstract: The role of Proniosomes in oral controlled drug delivery system is well accepted. Presently, an attempt was made to develop cephradine (CP) Proniosomes to prolong its duration of action with better efficacy. Overall, eighteen formulation trials were developed using variable quantities of sorbitol (F0S-F8S) and maltodextrin (F0M-F8M) carriers along with span60 and cholesterol. Trials were evaluated for powder flowability, drug entrapment efficiency and in vitro drug release. Based on the mentioned characteristics, formulations F4M and F4S were optimized. Stability test was performed on optimized Proniosomes for three months at temperature (2-8°C). Comparison for antimicrobial sensitivity against Staphylococcus aureus was also made between optimized and marketed conventional CP capsule. More than 80% drug release was observed in 22 hr in the trial formulations. The optimized CP Proniosomes were found to be highly stable with % drug entrapment efficiency of 78.60±0.15 and 88.41±0.19 respectively for F4M and F4S. The prepared Proniosomes possessed higher bactericidal activity against S. aureus than reference products (M1 and M2). In conclusion, CP Proniosomes have been successfully prepared using sorbitol/maltodextrin carrier. Sorbitol carrier exhibited marginally better drug entrapment efficiency and bactericidal activity than the maltodextrin trial and marketed brands. This effort offers improved drug delivery with the potential of more effective controlled therapy. Key words: Proniosomes, Cephradine, Nano-carriers, Niosomes, Bactericidal activity, Controlled drug delivery.

The Incorporation of Etanercept into a Porous Tri-Layer Scaffold for Restoring and Repairing Cartilage Tissue.

Cartilage diseases currently affect a high percentage of the world’s population. Almost all of these diseases, such as osteoarthritis (OA), cause inflammation of this soft tissue. However, this could be controlled with biomaterials that act as an anti-inflammatory delivery system, capable of dosing these drugs over time in a specific area. The objective of this study was to incorporate etanercept (ETA) into porous three-layer scaffolds to decrease the inflammatory process in this soft tissue. ETA is a blocker of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). For this reason, the scaffold was built based on natural polymers, including chitosan and type I collagen. The scaffold was grafted next to subchondral bone using hydroxyapatite as filler. One of the biomaterials obtained was also crosslinked to compare its mechanical properties with the non-treated one. Both samples’ physicochemical properties were studied with SEM, micro-CT and photoacoustic imaging, and their rheological properties were also compared. The cell viability and proliferation of the human chondrocyte C28/I2 cell line were studied in vitro. An in vitro and in vivo controlled release study was evaluated in both specimens. The ETA anti-inflammatory effect was also studied by in vitro TNF-α and IL-6 production. The crosslinked and non-treated scaffolds had rheological properties suitable for this application. They were non-cytotoxic and favoured the in vitro growth of chondrocytes. The in vitro and in vivo ETA release showed desirable results for a drug delivery system. The TNF-α and IL-6 production assay showed that this drug was effective as an anti-inflammatory agent. In an in vivo OA mice model, safranin-O and fast green staining was carried out. The OA cartilage tissue improved when the scaffold with ETA was grafted in the damaged area. These results demonstrate that this type of biomaterial has high potential for clinical applications in tissue engineering and as a controlled drug delivery system in OA articular cartilage.