Sustained Delivery System Research Articles

Dual drug delivery collagen vehicles for modulation of skin fibrosis in vitro

Single molecule drug delivery systems have failed to yield functional therapeutic outcomes, triggering investigations into multi-molecular drug delivery vehicles. In the context of skin fibrosis, although multi-drug systems have been assessed, no system has assessed molecular combinations that directly and specifically reduce cell proliferation, collagen synthesis and transforming growth factor β1 (TGFβ1) expression. Herein, a core–shell collagen type I hydrogel system was developed for the dual delivery of a TGFβ trap, a soluble recombinant protein that inhibits TGFβ signalling, and Trichostatin A (TSA), a small molecule inhibitor of histone deacetylases. The antifibrotic potential of the dual delivery system was assessed in an in vitro skin fibrosis model induced by macromolecular crowding (MMC) and TGFβ1. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and high performance liquid chromatography analyses revealed that ∼50% of the TGFβ trap and ∼30% of the TSA were released from the core and shell compartments, respectively, of the hydrogel system after 10 d (longest time point assessed) in culture. As a direct consequence of this slow release, the core (TGFβ trap)/shell (TSA) hydrogel system induced significantly (p < 0.05) lower than the control group (MMC and TGFβ1) collagen type I deposition (assessed via SDS-PAGE and immunocytochemistry), α smooth muscle actin (αSMA) expression (assessed via immunocytochemistry) and cellular proliferation (assessed via DNA quantification) and viability (assessed via calcein AM and ethidium homodimer-I staining) after 10 d in culture. On the other hand, direct TSA-TGFβ supplementation induced the lowest (p < 0.05) collagen type I deposition, αSMA expression and cellular proliferation and viability after 10 d in culture. Our results illustrate the potential of core–shell collagen hydrogel systems for sustained delivery of antifibrotic molecules.

Inhalable cryptotanshinone spray-dried swellable microparticles for pulmonary fibrosis therapy by regulating TGF-β1/Smad3, STAT3 and SIRT3 pathways

Cryptotanshinone (CTS) is a promising therapeutic option for pulmonary fibrosis (PF). However, clinical applications of CTS are limited owing to high photosensitivity and poor oral bioavailability. Pulmonary drug delivery, especially sustained pulmonary drug delivery, is promising for local treatment of chronic lung diseases. In this study, CTS was encapsulated in an optimized chitosan/L-leucine-based swellable microparticles (SMs) system, which exhibited an appropriate aerosolization performance, sustained release and storage stability. SMs enhanced the in vitro anti-fibrosis efficacy of CTS as shown by the improved cellular uptake. The effect of PF status on in vivo fate of the pulmonary delivered drug was also assessed. Pharmacokinetics and tissue distribution of oral and pulmonary delivery CTS in bleomycin-induced PF rats were compared. Pulmonary delivery exhibited high drug concentrations in pulmonary lesion areas, with reduced exposure to blood and non-targeted tissues after administration at a significantly lower dose compared with oral delivery. Moreover, PF pathological status enhanced activity of SMs, implying that pulmonary delivery was highly effective for PF treatment. Compared to oral delivery, Inhaled SMs showed comparable or even better efficacies at approximately 60-fold low dose compared with oral delivery. A sustained efficacy was observed under a prolonged administration interval (corresponding to half the total dose). Inhalation safety of SMs was established, and important mechanism-related signaling pathways against PF were investigated in vitro and in vivo. In summary, the findings showed that the developed CTS-loaded sustained pulmonary delivery system is a safe and effective strategy for chronic PF treatment.

Injectable In Situ Gelling System for Sustained Nicotine Delivery as a Replacement Therapy for Smoking Cessation.

Nicotine replacement therapy (NRT) is widely used to limit the withdrawal symptoms associated with cigarette smoking cessation. However, the available NRT formulations are limited by their short release profiles, requiring frequent administrations along with local side effects. Thus, the objective of this study is to develop an NRT formulation that offers prolonged, sustained nicotine release. Thermoresponsive in situ gelling systems containing nicotine were prepared using poloxamer 407 (P407) and poloxamer 188 (P188). The system was optimized using a three-factor, two-level full factorial design (23). A formulation composed of P407 (20% w/w), P188 (5% w/w), and loaded with nicotine (0.5% w/w) exhibited sol-to-gel transition at a suitable temperature close to physiological temperature (30 °C). The rheological analysis demonstrated a Newtonian-like flow at room temperature, suggesting ease of administration via injection, and semisolid gel status at physiological temperature. The optimized formulation successfully sustained nicotine in vitro release over 5 days following single administration. The findings suggest that poloxamer based in situ gelling systems are promising platforms to sustain the release of nicotine.

Osteoprotective effect of the marine alkaloid norzoanthamine on an osteoporosis model in ovariectomized rat

Norzoanthamine (NZ), an alkaloid that has been isolated from the marine cnidiaria Zoanthus sp., has been shown an interesting anti-osteoporotic activity. Although its mechanism of action is not yet clear, it seems that it is different from those of currently used drugs making it particularly interesting. Previous studies have been carried out mostly in vitro. Herein, we present an in vivo study that allows to check the real potential of NZ as a protector substance by direct application into ovariectomized rat bone using a sustained delivery system. Histological and histomorphometric results in ovariectomized rats showed higher bone quality as a result of greater number of trabeculae and osteogenic activity in the group implanted with NZ, compared to controls. In contrast with the untreated controls, NZ-treated groups showed a balanced osteoblast/osteoclast number ratio, similar to that found in the normal bone. These results suggest that NZ could be useful as adjunct to other osteoporosis treatments, but probably its main therapeutic role would be as preventive therapy against bone deterioration.

One-Step Fabrication of Hollow Spherical Cellulose Beads: Application in pH-Responsive Therapeutic Delivery.

The path to greater sustainability and the development of polymeric drug delivery systems requires innovative approaches. The adaptation and use of biobased materials for applications such as targeted therapeutic delivery is, therefore, in high demand. A crucial part of this relates to the development of porous and hollow structures that are biocompatible, pH-responsive, deliver active substances, and contribute to pain relief, wound healing, tissue regeneration, and so forth. In this study, we developed a facile single-step and water-based method for the fabrication of hollow spherical cellulose beads for targeted drug release in response to external pH stimuli. Through base-catalyzed deprotection, hydrophobic solid and spherical cellulose acetate beads are transformed into hydrophilic cellulose structures with a hollow interior (wall thickness: 150 μm and inner diameter: 650 μm) by a stepwise increment of temperature and treatment time. Besides the pH-responsive fluid uptake properties, the hollow cellulose structures exhibit a maximum encapsulation efficiency of 20–85% diclofenac (DCF), a nonsteroidal anti-inflammatory drug, used commonly to treat pain and inflammatory diseases. The maximum amount of DCF released in vitro increased from 20 to 100% when the pH of the release medium increased from pH 1.2 to 7.4. As for the DCF release patterns and kinetic models at specific pH values, the release showed a diffusion- and swelling-controlled profile, effortlessly fine-tuned by external environmental pH stimuli. Overall, we show that the modified beads exhibit excellent characteristics for transport across the gastrointestinal tract and enhance the bioavailability of the drug. Their therapeutic efficacy and biocompatibility are also evident from the studies on human fibroblast cells. We anticipate that this platform could support and inspire the development of novel sustainable and effective polysaccharide-based delivery systems.

Design of the lentivirus-driven sustained LR12 delivery system for TREM-1 inhibition for palliating atherosclerosis.

Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) has been a potential target in the management of pathophysiology and clinical sequelae of atherosclerosis. LR12 peptide effectively blocks ligand-TREM-1 interaction; however, the short half-life of LR12 is a major hurdle in its translational application in atherosclerosis management warranting new methods for sustained bioavailability in clinical applications. The present study reports a novel method of packing the coding sequence of LR12 in a lentiviral system to ensure a sustained expression and bioavailability for effective TREM-1 inhibition. Lentivirus vector systems (LV-LR12 and LV-SP) for the expression of LR12 peptide and SP (scrambled peptide) were successfully designed, constructed, and tested in vitro in smooth muscle cells (SMCs). Viral amounts obtained were 703.6 ± 145.12 and 609.3 ± 145.93ng/ml p24 for LV-LR12 and LV-SP, respectively which correspond to ~ 107IFU/ml for both vectors. Dot blot assay revealed significantly increased expression of LR12-FLAG and SP-FLAG in 125μg total protein which was doubled in 250μg protein with respect to un-transduced SMCs suggesting the sustained release of LR12/SP as confirmed by ELISA. Cellular expression of LR12-FLAG and SP-FLAG displayed 8.44-fold and 7.55-fold increase, respectively compared to the control SMCs. The findings demonstrated a promising strategy for packing the LR12 coding sequence in lentiviral vector for TREM-1 inhibition for the management of atherosclerosis and other inflammatory diseases.

Trends and perspectives in bio- and eco-friendly sustainable nanomaterial delivery systems through biological barriers

This review summarizes and provides perspectives on the recent efforts towards the greener synthesis and biomedical delivery applications of various nanoparticles with respect to sustainability.

Continuous local antibiotic perfusion: A treatment strategy that allows implant retention in fracture-related infections

Fracture-related infections are difficult to treat because of the formation of biofilms around implants. Systemic antibiotics are notoriously ineffective against biofilms due to their insufficient penetration of tissues with poor vascularity. The goal of treating fracture-related infections is to achieve bone union while retaining the implant. Our proposal of continuous local antibiotic perfusion is a sustained local delivery system of sufficient antibiotics to bone and soft tissue infection sites, including to bone marrow via needles as intra-medullary antibiotics perfusion and to soft-tissue via double-lumen subcutaneous tubes as intra-soft tissue perfusion. In this study, we examined the outcomes of 40 patients treated for fracture-related infections using continuous local antibiotic perfusion between 2015 and 2021 at Steel Memorial Hirohata Hospital, Himeji, Japan. The antibiotic used for continuous local antibiotic perfusion was gentamicin in all cases. Implant removal was required in five patients. Two patients required toe amputation and knee arthrodesis, while the remaining 38 patients achieved fracture union. Only one case of transient acute renal injury as a systemic side effect was observed, but it soon resolved. The blood concentration of gentamicin could be adjusted to less than the trough level. Continuous local antibiotic perfusion is a novel local drug delivery system that has the potential of delivering sufficient concentrations of antibiotics with few systemic side effects; it is a useful option for the treatment of fracture-related infections.

Development and evaluation of ketoprofen loaded floating microspheres for sustained delivery

Present study was designed with the objective of formulating floating microspheres of ketoprofen for sustaining the drug release. Ketoprofen is a cyclooxygenase inhibitor widely employed for treating arthritis. It has a bitter taste and off taste and also irritates the gastric mucosa. Its half-life is only 1–2 hrs. Floating microspheres of ketoprofen would help prevent gastric irritation, mask the taste of the drug and decrease the dosing frequency. Formulation and optimization of microsphere was done by employing sodium alginate and chitosan as the polymer by application of ionotropic gelation method and assessed for various properties. The outcome of optimization shows a smooth surface and narrow size distribution. The DSC and FTIR analysis indicated that the polymer was not incompatible with the drug. After 8 h, 92.74 % of the medicament was released in vitro. Based on the findings of this study, Chitosan and Sodium alginate -loaded microspheres of ketoprofen may be fruitfully used to develop floating sustained delivery systems. The formulation, MF7 was found to be a promising formulation, based on its percentage yield, percentage buoyancy, and floating lag time and other evaluated parameters. The prepared floating microspheres are suitable for sustained drug delivery of ketoprofen, and adapted well for different intragastric conditions. The ionic gelation method proved to be a suitable method for fabricating ketoprofen microspheres for sustained drug delivery, thereby achieving the objective of the study.

Effective Extension Sustainability in the face of COVID-19 Pandemic in Smallholder Agricultural Markets

Abstract: The effects of COVID-19 have tested and crushed the earlier achievement in sustaining the agricultural and extension delivery system globally. COVID-19 has pressed a reset panel on the extension services more especially among the smallholder farmers who are already underprivileged. Specifically, this review paper aims to analyse studies on the sustainability of agricultural extension delivery systems in face of the COVID-19 crisis. The various theories and factors advanced in discussing sustainable agricultural extension delivery systems, and how they contribute to improved production and productivity to end poverty have been addressed. The COVID-19 mitigation strategies and their effect on agricultural extension sustainability have been laid bare. No single sustainability theory can explain how COVID-19 has disrupted the extension delivery systems. The service providers and farmers have had their effects differently, and all players have followed mitigation to the best of their knowledge. Extension delivery has undergone numerous modifications over the years to better meet the demands of farmers and the changing nature of the markets in which they operate. In order to provide effective service delivery and outcomes to farmers, collective involvement of various stakeholders is necessary since no single player can achieve effective extension sustainability alone due to the diverse nature of the challenges, which are mainly influenced by factors such as geographical location, poverty, and social status among others. Therefore, appropriate approaches should be selected based on the needs of farmers and the market dynamics of a specific economic orientation in a given area. We conclude that effective and sustainable extension delivery systems require many combined theories, support functions, formal and informal rules, and regulations involving all extension-based stakeholders. Keywords: Sustainability, COVID-19, smallholder farmers, agricultural market systems, extension services

Sustained Delivery of Lactoferrin Using Poloxamer Gels for Local Bone Regeneration in a Rat Calvarial Defect Model.

Lactoferrin (LF) is a multifunctional milk glycoprotein that promotes bone regeneration. Local delivery of LF at the bone defect site is a promising approach for enhancement of bone regeneration, but efficient systems for sustained local delivery are still largely missing. The aim of this study was to investigate the potential of the poloxamers for sustained delivery of LF to enhance local bone regeneration. The developed LF/poloxamer formulations were liquid at room temperature (20 °C) transforming to a sustained releasing gel depot at body temperature (37 °C). In vitro release studies demonstrated an initial burst release (~50%), followed by slower release of LF for up to 72 h. Poloxamer, with and without LF, increased osteoblast viability at 72 h (p < 0.05) compared to control, and the immune response from THP-1 cells was mild when compared to the suture material. In rat calvarial defects, the LF/poloxamer group had lower bone volume than the controls (p = 0.0435). No difference was observed in tissue mineral density and lower bone defect coverage scores (p = 0.0267) at 12 weeks after surgery. In conclusion, LF/poloxamer formulations support cell viability and do not induce an unfavourable immune response; however, LF delivery via the current formulation of LF200/poloxamer gel did not demonstrate enhanced bone regeneration and was not compatible with the rat calvarial defect model.

Deep Eutectic Solvents as Active Pharmaceutical Ingredient Delivery Systems in the Treatment of Metabolic Related Diseases.

Metabolic related diseases such as cancer, diabetes mellitus and atherosclerosis are major challenges for human health and safety worldwide due to their associations with high morbidity and mortality. It is of great significance to develop the effective active pharmaceutical ingredient (API) delivery systems for treatment of metabolic diseases. With their unique merits like easy preparation, high adjustability, low toxicity, low cost, satisfactory stability and biodegradation, deep eutectic solvents (DESs) are unarguably green and sustainable API delivery systems that have been developed to improve drug solubility and treat metabolic related diseases including cancer, diabetes mellitus and atherosclerosis. Many reports about DESs as API delivery systems in the therapy of cancer, diabetes mellitus and atherosclerosis exist but no systematic overview of these results is available, which motivated the current work.

Preparation and functional evaluation of electrospun polymeric nanofibers as a new system for sustained topical ocular delivery of itraconazole

Due to the rapid clearance of external agents from the surface of the cornea, conventional ocular formulations usually require frequent and long duration of administration to achieve a therapeutic level of the drug on the cornea which can be conquered using prolonged-release nanofibrous inserts. In the present study, for the first time, polymeric nanofibers of itraconazole (ITZ), a potent triazole antifungal agent, were prepared as ocular inserts to enhance the topical ocular delivery of the drug. Three different nanofibers were prepared by electrospinning using polyvinyl alcohol-cellulose acetate and polycaprolactone-polyethylene glycol 12 000 polymeric blends. Nanofibers indicated uniform structures with the mean diameter ranging between 137 and 180 nm. Differential scanning calorimetry and Fourier-transform infrared spectroscopy confirmed the amorphous state of the drug in the formulations and the no drug-polymer interaction. Appropriate stability, suitable flexibility, and 2.2–3.9 MPa tensile strength were observed. Formulations indicated antifungal efficacy against Candida albicans and Aspergillus fumigatus and cell viability >70% at different concentrations. Results of bioassay against Candida albicans exhibited prolonged in vitro release of 50–70% of ITZ for almost 55 days. The results suggested that the nanofibers could be considered suitable for prolonged delivery of the ITZ as an antifungal requiring frequent and long duration of administration.

Polymer Nanofibers for Biomedical Applications: Advances in Electrospinning

Background: The demand for novel biomaterials has been exponentially rising in the last years as well as the searching for new technologies able to produce more efficient products in both drug delivery systems and regenerative medicine. Objective: The technique that can pretty well encompass the needs for novel and high-end materials with a relatively low-cost and easy operation is the electrospinning of polymer solutions. Methods: Electrospinning usually produces ultrathin fibers that can be applied in a myriad of biomedical devices including sustained delivery systems for drugs, proteins, biomolecules, hormones, etc that can be applied in a broad spectrum of applications, from transdermal patches to cancer-related drugs. Results: Electrospun fibers can be produced to mimic certain tissues of the human body, being an option to create new scaffolds for implants with several advantages. Conclusions: In this review, we aimed to encompass the use of electrospun fibers in the field of biomedical devices, more specifically in the use of electrospun nanofibers applications toward the production of drug delivery systems and scaffolds for tissue regeneration.

Sustained doxorubicin delivery system to breast tumor cancer cell based on a novel cationic molecularly imprinted polymer

In this study, Poly(methacrylic acid-co-diallyldimethylammonium chloride) or Poly(MAA-PDDA) was synthesized as a cationic molecularly imprinted nano-polymer. After in vitro assays such as cytotoxicity assay and hemolysis activity test, this imprinted nano-polymer was examined for targeted Doxorubicin (DOX) delivery in BALB/c mice bearing MCF7 human breast carcinoma cells. In vivo studies of synthesized nanoparticles on BALB/c mice showed their selectivity. Also, it was found that tumor growth delay (TGD) improved from 1.11 in DOX treated group to 2.82 in cationic polymer combined with DOX. Imprinted cationic polymer provides remarkable prevention of tumor growth. Investigating drug deposition in various tissues showed that DOX concentration was considerably more in tumors than in other tissues.

Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release

The preferable choice of sustained peptide delivery systems is generally polymer-based microspheres in which their large particle size, wide size distribution, low drug encapsulation efficacy, poor colloidal stability, and undesirable burst release eventually hinder their clinical translation. In this study, a nanoscale ternary Lixisenatide (Lix) sustained delivery system based on strong multivalent interactions (electrostatic and coordination complexation) among small molecular phytic acid (PA), Lix and Fe3+ was developed. Flash nanocomplexation (FNC) was utilized to facilitate the rapid and efficient mixing of the three components and kinetically control the assembly process that enabled dynamic balance of two competitive chemical reactions with different kinetic rates (slow chemical reaction of PA/Lix and fast chemical reaction of PA/Fe3+) to generate structural uniform ternary nanoparticles and avoid heterogeneous complexes. By tuning the mixing conditions (i.e., flow rate, mass ratio, concentration, pH value, etc.), the ternary PA/Lix/Fe3+ nanoparticles were assembled with reproducible production in a manner of high uniformity and scalability, achieving small size (∼50 nm), uniform composition (PDI: ∼0.12), favourable colloidal stability, high encapsulation efficiency (∼100%), and tunable drug release kinetics. The optimized formulation exhibited a minor Lix release (<20%) in the first day and extended peptide release period over 8 days. Unexpectedly, upon a single injection administration, the as-prepared formulation (600 μg/kg) rapidly brought the high BGL (∼30 mmol/L) back to normal range (<10 mmol/L) within the initial 6 h and achieved a 180 h glycemic control in T2D mouse model. Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment.

Targeting of radio-enhancing drugs

Objective Toxicity to normal tissue is frequently the dose-limiting factor in the chemotherapy and mixed modality treatments of cancer. If the radio-enhancing drug could be localized at the disease site and released slowly over time, then systemic drug toxicities could be decreased while simultaneously maintaining high drug concentrations in the tumor. These considerations support a role for a sustained release intra-tumoral delivery systems for the delivery of radio-enhancing drugs. Methods Two approaches aimed at achieving the end of localizing the radio-enhancing drug to the tumor are described. First, nanoparticles, which have a prolonged circulation time and facility for enhanced tumor targeting. Structural defects in the walls of the tumor vasculature allow the passage of particles too large to pass through the walls of normal blood vessels. This characteristic of tumor blood vessels, referred to as the enhanced permeability and retention (EPR) effect, allows relatively large entities (typically liposomes, nanoparticles, and macromolecular drugs) to pass from the blood vessels to tumor tissue and as a result nanoparticles accumulate in the tumor while being excluded from normal tissue. Second, biodegradable implanted polymers. In these devices, the radio-enhancing drug is physically trapped within the polymer matrix which is implanted in the tumor. The drug is released as the polymer degrades in response to its local environment. The degradation rate of the polymer device can be adjusted to control the rate of drug release. By this means, the level of radio-enhancing drug can be maintained at the tumor site for the duration of radiation treatment. Results and conclusions Results of experiments indicate that for both methods tumor control could be optimized by maintaining the radio-enhancing drug at a useful concentration in the tumor over a period of time compatible with the duration of fractionated radiation treatment. These studies have provided proof of principle support for the further development of this approach. To date, while some of the methods and devices for drug delivery described in this paper have been involved in clinical trials, none have so far been developed for routine clinical application.

Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles.

Synthetic and naturally occurring nano-sized particles present versatile vehicles for the delivery of therapy in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune response, and therapeutic cargo, but rapid clearance from the body and limited efficacy remain a major challenge. This highlights the need for a local sustained delivery system for nanoparticles (NPs) and extracellular vesicles (EVs) at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity. Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand. In this review, we highlight the prospect of the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.

PEI-PEG-Coated Mesoporous Silica Nanoparticles Enhance the Antitumor Activity of Tanshinone IIA and Serve as a Gene Transfer Vector.

Tanshinone IIA (TanIIA) and gene therapy both hold promising potentials in hepatocellular carcinoma (HCC) treatment. However, low solubility and poor bioavailability of TanIIA limit its clinical application. Similarly, gene therapy with GPC3-shRNA, a type of short hairpin RNAs (shRNAs) capable of silencing the glypican-3 (GPC3) expression, is seriously limited due to its susceptibility to nuclease degradation and high off-target effects. In the present study, polyethyleneimine (PEI)-polyethylene glycol (PEG)-coated mesoporous silica nanoparticles (MSN-PEG) were used as a drug carrier. By encapsulating TanIIA into MSN-PEG, we synthesized MSN-TanIIA-PEG nanoparticles and observed the involved characteristics. This was followed by exploration of antitumor activity on the HepG2 cell lines in vitro. Meanwhile, in order to construct GPC3-shRNA plasmids, a shRNA sequence targeting GPC3 was synthesized and cloned into the pSLenti-U6 vector. Accordingly, the performance of MSN-PEG as a gene transfer carrier for GPC3-shRNA gene therapy of HCC in vitro was evaluated, including transfection efficiency and DNA binding biological characteristics. The results indicated successful encapsulation of TanIIA in MSN-PEG, which had satisfactory efficacy, favorable dispersity, suitable particle size, and sustained release effect. The in vitro anti-HCC effects of nano-TanIIA were greatly improved, which outperformed free-TanIIA in terms of proliferation and invasion inhibition, as well as apoptosis induction of HCC cells. As expected, MSN-PEG possessed excellent gene delivery capacity with good binding, release, and protection from RNase digestion. Using MSN-PEG as a gene carrier, the plasmids were successfully transfected into HepG2 cells, and both the mRNA and protein expressions of GPC3 were significantly downregulated. It was thus concluded that a sustained release TanIIA delivery system for HCC treatment was synthesized and that MSN-PEG could also serve as a gene transfer carrier for gene therapy. More interestingly, MSN-PEG may be a potential delivery platform that combines TanIIA and GPC3-shRNA together to enhance their synergistic effect.

Injectable in situ gelling delivery system for the treatment of jawbone infections.

Aim: A polymeric in situ gelling delivery system for localized and sustained delivery to jawbone infections was developed. Materials & methods:In situ gelling delivery systems were prepared using either Poly(dl-lactic acid)or chitosan and Pluronic F127/Pluronic F68. Metronidazole nanoparticles were prepared using poly(dl-lactide-co-glycolide)or chitosan. Poly(dl-lactide-co-glycolide) was used for microparticles. Particles were characterized for size, chargeand morphology. Results: Viscosity and yield stress of the gels were 0.4Pa.s and 2Pa, respectively, with 70% cell viability over 72h. Around 90% of loaded metronidazole was released at a sustained rate over 1 week. Conclusion: Use of appropriate amount of nano/microparticles in the gel resulted in a sustained release over a period of 1 week - needed for jawbone infection.