Sustained Delivery System Research Articles

FORMULATION AND EVALUATION NASAL IN SITU GEL OF RIZATRIPTAN

Rizatraptan, a 5-HT antagonist is an anti migraine drug. Rizatriptan undergoes hepatic first pass metabolism, hence it shows poor bioavailability. In this study attempt has been done to improve bioavailability by formulating nasal in-situ gel. Formulation was developed to reduce the mucociliary clearance by using mucoadhesive polymer in gel, thereby increasing the contact of formulation with nasal mucosa and hence improving the absorption of drug. The in situ gel was formulated by using 2 factor (i.e.% of carbopol 934P and % of poloxamer 407) 3 level center composite design. All the formulated design point formulations exhibit thermo reversible gelation property. Gels were characterized by permeation studies, pH, % drug content, mucoadhesive force, gel strength, in vitro diffusion, ex vivo diffusion, stability study. Rheological study of gel formulation indicated that increase in polymer concentration increases the viscosity, gel strength was found in range of 110-130 sec., Spectral study revealed no interaction between drug and polymer. Various responses like T50%(Y1), T(80%Y2), ‘n’ of peppa’a equation(Y3), ‘k’ of first order and ‘n’ of higuchi (Y5) were analyzed to obtain optimized formulation. Optimized formulation(OF) followed first order drug diffusion and theoretically obtained drug release profile for 8 Hr. on the base of dose calculation Stability study indicates that there was no significant change in the Rizatriptan benzoate. Rizatriptan benzoate formulated as bioadhesive solution for nasal administration could have potential to avoid first pass effect than oral route, thus improve bio availability of drug and as a safe and sustained release nasal delivery system to control migraine

Development of nano-sized ketoprofen lysine incorporated Eudragit® S100 nanomedicine by double emulsion solvent evaporation and in vitro characterization

Context: Pain has a very important effect on the biological, psychological, sociological and economic situation of a patient. Nanoparticles (NPs) are being extensively investigated as drug delivery systems worldwide for pharmaceutical applications. Aims: To design and compare the release characteristics of sustained-release formulations of ketoprofen lysine (KL) NPs. Methods: KL-Eudragit® S100 NPs were produced by double emulsion solvent evaporation method. The physicochemical characteristics of NPs were studied. Results: Particle size of NPs prepared was in the range of 99 and 141 nm. Encapsulation efficiency (%) was obtained (76%) for NP formulations prepared. Weibull models were determined to be the most appropriate kinetic models for NP containing KL. KL-loaded NPs demonstrated nanostructural character and NPs showed extended release of KL. Conclusions: NPs developed were found to be stable and representing a promising system for sustained delivery of KL.

Bimodal antibacterial system based on quaternary ammonium silane-coupled core-shell hollow mesoporous silica

Hollow mesoporous silica (HMS) have been extensively investigated as a biomaterial for drug delivery. The present study developed quaternary ammonium silane-grafted hollow mesoporous silica (QHMS) to create a metronidazole (MDZ) sustained delivery system, MDZ@QHMS, with bimodal, contact-kill and release-kill capability. The QHMS was assembled through a self-templating method. Metronidazole was incorporated within the QHMS core using solvent evaporation. Antibacterial activities of the MDZ@QHMS were investigated using single-species biofilms of Staphylococcus aureus (ATCC25923), Escherichia coli (ATCC25922) and Porphyromonas gingivalis (ATCC33277). The MDZ@QHMS maintained a hollow mesoporous structure and demonstrated sustained drug release and bacteridal actvity against the three bacterial strains at a concentration of 100 μg/mL or above. These nanoparticles were not relatively cytotoxic to human gingival fibroblasts when employed below 100 µg/mL. Compared with HMS, the MDZ@QHMS system at the same concentration demonstrated antibiotic-elution and contact-killing bimodal antibacterial activities. The synthesized drug carrier with sustained, bimodal antibacterial function and minimal cytotoxicity possesses potential for localized antibiotic applications. Statement of SignificanceThe present study develops quaternary ammonium silane-grafted hollow mesoporous silica (QHMS) to create a metronidazole (MDZ) sustained delivery system, MDZ@QHMS, with bimodal, contact-kill and release-kill capability. This system demonstrates sustained drug release and maintained a hollow mesoporous structure. The synthesized drug carrier with sustained, bimodal antibacterial function and excellent biocompatibility possesses potential for localized antibiotic applications.

In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment

Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. To test the hypothesis that a sustained delivery system of diltiazem hydrochloride may be helpful for the treatment of chronic anal fissures, in the present study we evaluated the potential of gels containing diltiazem hydrochloride entrapped in microsponges. Such microsponges were based on Eudragit RS 100 and the effect of some formulation variables was assessed by a 23 full factorial screening design. An optimized formulation of diltiazem hydrochloride microsponges was dispersed in Methylcellulose 2% or Poloxamer 407 20% and the resulting gels (micro-l-diltiazem hydrochloride 2%) were subjected to in vitro drug release, ex vivo permeability and drug deposition after application on porcine rectal mucosa. The results showed a prolonged release up to 24 h from micro-l-diltiazem hydrochloride at 2% in the gels. The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy.

Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules for the Treatment of Ocular Diseases.

The objective of this study is to design, develop, and synthesize novel random triblock (RTB) copolymers for sustained delivery of macromolecules. RTB copolymers have not been utilized for the delivery of macromolecules for ocular diseases. RTB copolymers comprising of polyethylene glycol, glycolide, and ɛ-caprolactone blocks were synthesized and assessed for their molecular weights and purity using 1H-NMR spectroscopy, gel permeation chromatography, FTIR (functionality), and XRD (crystallinity). No toxicity was observed when ocular cell lines were treated with RTB copolymers. These materials were applied for encapsulation of peptides and proteins (catalase, IgG, BSA, IgG Fab fragment, lysozyme, insulin, and octreotide) in nanoparticles. Particle size ranged from 202.41 ± 2.45 to 300.1 ± 3.11nm depending on the molecular size and geometry of proteins/peptides. Polydispersity indices were between 0.26 ± 0.02 and 0.46 ± 0.07 respectively. Percentage entrapment efficiency and drug loading ranged from 83.44 ± 2.24 to 45.35 ± 5.53 and 21.56 ± 0.46 to 13.08 ± 1.35 respectively depending on molecular weights of peptides or proteins. A sustained in vitro release of macromolecule was observed over 3-month period. These results suggest that RTB copolymers may be suitable for sustained delivery systems for various macromolecules for different diseases including ocular diseases.

Loading icariin on titanium surfaces by phase-transited lysozyme priming and layer-by-layer self-assembly of hyaluronic acid/chitosan to improve surface osteogenesis ability.

PurposeIcariin (ICA) is one of the main active constituents of Herba Epimedii for improving osteogenesis. It is necessary to create a simple and efficient method to load ICA onto the surface of titanium (Ti) implant. The purpose of this study was to establish a local ICA delivery system via a layer-by-layer (LbL) self-assembly system on phase-transited lysozyme (PTL)-primed Ti surface.Materials and methodsA PTL nanofilm was first firmly coated on the pristine Ti. Then, the ICA-loaded hyaluronic acid/chitosan (HA/CS) multilayer was applied via the LbL system to form the HA/CS-ICA surface. This established HA/CS-ICA surface was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The ICA release pattern of the HA/CS-ICA surface was also examined. MC3T3-E1 osteoblast culture test and a rat model were used to evaluate the effects of the HA/CS-ICA surface in vitro and in vivo.ResultsSEM, XPS and contact angle measurement demonstrated successful fabrication of the HA/CS-ICA surface. The HA/CS-ICA surfaces with different ICA concentrations revealed a controlled release profile of ICA during a 2-week monitoring span. Osteoblasts grown on the coated substrates displayed higher adhesion, viability, proliferation and ALP activity than those on the polished Ti surface. Furthermore, in vivo histological evaluation revealed much obvious bone formation in the ICA-coated group by histological staining and double fluorescent labeling at 2 weeks after implantation.ConclusionThe present study demonstrated that ICA-immobilized HA/CS multilayer on the PTL-primed Ti surface had a sustained release pattern of ICA which could promote the osteogenesis of osteoblasts in vitro and improve early osseointegration in vivo. This study provides a novel method for creating a sustained ICA delivery system to improve osteoblast response and osseointegration.

Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Objective: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.Significance: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.Methods: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.Results: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.Conclusions: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.

Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect

ABSTRACTObjectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis.Methods: The new carrier has a hydroxyapatite core, with alternating layers of siRNA and a cationic peptide. The siRNA used here targets secreted protein acidic and rich in cysteine (SPARC), a key matricellular protein involved in the regulation of collagen fibrillogenesis and assembly. We have also used FRET studies to elucidate the fate of the particles inside cells, including the mechanistic details of layer-by-layer detachment.Results: In vitro studies using murine conjunctiva fibroblasts show sustained release over 2 weeks, and that such released siRNA sustained SPARC knockdown without affecting cell growth, and maintained siRNA presence in the cells for at least two weeks with a single-dose treatment. Release studies of siRNA from particles in vitro gave insight on how the particles delivered prolonged gene-silencing effects.Conclusion: A single treatment of the layer-by-layer nanoparticle designed can achieve sustained gene silencing over 2 weeks. Localized delivery of stabilized siRNA with sustained-release capabilities opens the door for many other applications of siRNA-based gene regulation.

Porous Oral Drug Delivery System: Tablets

One of the most active and promising areas of research in this pharmaceutical field is the application of porous structures in solid-state pharmaceuticals, particularly given the large number of existing and emerging therapeutic molecules that are classified as poorly soluble, including approximately 40% of the top 200 oral drugs globally. Porous compacts have been extensively studied for pharmaceutical applications due to their good biocompatibility, biodegradability, and satisfactory solubility at low toxicity. Porous compacts can be filled in hard gelatine capsule shells or processed to form tablets. Porous formulations in the tablet form showed good biocompatibility without causing undesirable side effects in biological systems. The porous particulate drug formulations can be of both types such as immediate or sustained release delivery system. The evolution of porous matrices as potential drug delivery systems continues with ongoing efforts in improving the loading and controlled release of therapeutics, with particular interest in targeted delivery. The mechanism of immediate release from porous tablets can be attributed to quick entry of water into porous matrix which causes rapid disintegration and dissolution of the tablet. The oral bioavailability of poorly water-soluble drugs is enhanced by porous compacts. Porous compacts are also used to enhance the dissolution of relatively insoluble drugs.

Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems.

Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products. Here, we present a review of the efficacy of the plant based-nanomaterials in the management of wounds and discuss the involved therapeutic targets. For this purpose, a profound search has been conducted on in vitro, in vivo, and/or clinical evidences evaluating the efficacy and pharmacological mechanisms of natural product-based nanostructures on different types of wounds. Different pharmacological targets are involved in the wound healing effects of herbal-based nanostructures, including suppressing the production of inflammatory cytokines and inflammatory transduction cascades, reducing oxidative factors and enhancing antioxidative enzymes, and promoting neovascularization and angiogenic pathways through increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Moreover, nanostructure of plant extracts and their phytochemicals can enhance their bioavailability, control their release in the form of sustained delivery systems to the wound site, and enhance the permeability of these therapeutics to the underlying skin layers, which are all necessary for the healing process. Overall, various plant extracts and their natural compounds, used in nanoformulations, have demonstrated high activity in the management of wounds and thus can be assumed as future pharmaceutical drugs.

PLGA film/Titanium nanotubues as a sustained growth factor releasing system for dental implants.

Ti-based implants sometimes fail to integrate with surrounding bone tissue due to insufficiency of new bone formation and surface bonding. To overcome this problem, this research focused on establishing a sustained bone growth factor delivery system by applying anodized TiO2 nanotube arrays and PLGA film on the titanium implant surface. TiO2 nanotube arrays were made by anodic oxidation method, and were then filled with rhBMP2 by vacuum freeze-drying. Next, PLGA was deposition on the surface of this material. The designed system was characterized, pharmacokinetic release rate of rhBMP2 was determined. Adhesion, proliferation, and differentiation activity of osteoblasts cultured on the new surfaces and traditional titanium surfaced were compared. SEM showed that a surface of TiO2 nanotube arrays were successfully generated. PLGA membranes of 50 nm, 250 nm, 800 nm thickness were successfully deposited on the surfaces of TiO2 nanotube layers by using 1%, 3%, 10% PLGA solutions. PLGA film of 250 nm thickness showed ideally controlled release of rhBMP2, lasting for 4 weeks. Furthermore, 250 nm thickness PLGA film improved osteoblast adhesion, proliferation, and levels of alkaline phosphatase. In conclusion, the PLGA film / TiO2 nanotube growth factor delivery system can effectively sustain the release of rhBMP-2, and promote proliferation and differentiation of MC3T3-E1 osteoblasts.

Polymeric and Non Polymeric Injectable In-situ Forming Implant Systems for Sustained Delivery of Lornoxicam: In vitro and In vivo Evaluation.

Formulation of injectable In situ forming implant (ISI) systems of lornoxicam for dental and postoperative pain management to decrease dosing frequency and increase patient compliance. Polymeric in situ implant solutions were prepared using different concentrations and inherent viscosities of Poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG) using 22X4 factorial experimental design. Nonpolymeric systems were prepared using different concentrations of lipids like cetyl alcohol and stearyl alcohol and also sucrose acetate isobutyrate (SAIB) using 32 factorial experimental design. In vitro release study, rheological measurement, syringeability assessment and effect of γ-sterilization were used for evaluation of the prepared formulae. In vivo pharmacokinetic study of lornoxicam from the most optimum formula was conducted in a rabbit model using HPLC analysis of blood samples. Polymeric systems showed high burst release followed by very slow release rate over 72 hours. Formula I 24 (containing SAIB 80% (w/w)) showed relatively low burst release followed by diffusion controlled release pattern, low viscosity, Newtonian flow behavior and good syringeability. γ- sterilization had no significant effect on the in vitro release and the physical nature of the most optimum formula. In vivo study concluded that intramuscularly injected In situ implant formula I 24 showed prolonged release pattern compared to the marketed product which was indicated by the increased Tmax and the extended mean residence time. Lornoxicam ISI systems could be promising as convenient injectable sustained release delivery systems for dental and postoperative pain management.

Formulation, In-Vitro and Ex-Vivo Evaluation of Tretinoin Loaded Cubosomal Gel for the Treatment of Acne.

The current work was attempted to formulate and evaluate the topical sustained release delivery systems called cubosomes containing Tretinoin for the acne treatment. The recent patents on various formulations of tretinoin (EP0408370A2) helped in selecting a new formulation and evaluation. Tretinoin loaded cubosomes were prepared by bottom-up technique, using varying the concentration of lipid and surfactant and keeping the drug concentration constant, a total of nine formulations of tretinoin was developed. These preparations were evaluated for surface charge, particle size, particle morphology, encapsulation efficiency, in-vivo and in-vitro release studies of gel enriched with cubosome dispersion. Finally, the stability studies of cubosomal gel were performed on optimized formulations. Significant result were obtained with tretinoin formulation as the drug is lipophilic, so it gives more depot effect on the epidermis and good retention property. The data obtained from the formulations showed that formulation TCF-5 was the optimized formulation which exhibited better drug release and entrapment efficiency. It can be concluded that cubosomes offer benefits of quick onset as well as the maximal release of drug with fewer side effects. Thus, cubosomes represent a capable transporter having the property to sustain the release of drug, potential to localize the drug in the skin with a possible clinical application for acne vulgaris treatment due to cubosome depot effect on the epidermis.

Modifiable natural gum based microgel capsules as sustainable drug delivery systems

Few hundred micrometer size microgel capsules from natural locust bean gum (LBG) was synthesized by means of divinyl sulfone (DVS) crosslinking in a surfactant free cyclohexane medium with 100% yield in 1 h. These LBG microgel capsules were chemically modified with different numbers of linear amine containing modifying agents such as ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetraamine (TETA) and branched polyethyleneimine (PEI) to induce cationic character for LBG microgels. The biggest change in zeta potential of LBG microgels that is +44.9 mV from −17.67 mV was observed upon the modification of LBG microgels with branched PEI (LBG/PEI). The blood compatibility studies were revealed that bare LBG microgels possess a good blood compatibility with non-hemolytic value, 0.96 ± 0.15%, and high blood clotting index, 87.35 ± 4.10%, whereas the blood compatibility of LBG/PEI microgels was found to be slightly-hemolytic, 4.96 ± 1.03%, and also moderate blood clotting index, 65.98 ± 98%. Additionally, sodium diclofenac (SDC) as a model drug was loaded into the LBG based microgels by directly loading from solution (absorption) and by chemical conjugation methods for in vitro release studies at physiological conditions, pH 7.4 at 37.5 °C A longer, and sustainable drug release profiles were obtained from chemical drug conjugated LBG microgels and the amine modified LBG microgels.

Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy.

In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity. Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite). PCL microparticles were prepared by a solvent evaporation method (size 50 - 100µm). The gel was characterized using SEM, FTIR, XRD and TGA analysis. Dox-alg composite gel showed good syringeability and gel formation properties. Burst release was observed for both drugs within 24 h followed by sustained release till day 21. Doxorubicin released from composite showed considerable cytotoxic effect. Cell uptake was confirmed by confocal microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen released from composite gel was compared with the free drug. An injection of dox-alg composite gel in the tissue would fill the void created after tumor removal surgery, prevent the resuscitation of remnant cancerous cells and reduce inflammation. Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy.

Economic and Environmental Evaluation of a Brick Delivery System Based on Multi-Trip Vehicle Loader Routing Problem for Small Construction Sites

While large construction sites have on-site loaders to handle heavy and large packages of bricks, small brick manufacturers employ a truck-mounted loader or sometimes deploy a loader truck to accompany normal brick delivery trucks to small construction sites lacking on-site loaders. It may be very challenging for small contractors to manage a sustainable delivery system that is both cost-effective and environmentally friendly. To address this issue, this paper proposes to solve a multi-trip vehicle loader routing problem by uniquely planning routes and schedules of several types of vehicles considering their synchronized operations at customer sites and multi trips. This paper also evaluates the sustainability of the developed model from both economic and environmental perspectives. Case studies based on small construction sites in the Middle East demonstrate applications of the proposed model to make the most economical plans for delivering bricks. Compared to the single-trip vehicle loader routing problem, the proposed model reduces, on average, 18.7% of the total delivery cost while increasing CO2 emission negligibly. The economic benefit is mainly achieved by reducing the required number of vehicles. Brick plant managers can use the proposed mathematical model to plan the most cost-effective delivery schedules sustainably while minimizing negative environmental effects.

Incorporation of Synthetic mRNA in Injectable Chitosan-Alginate Hybrid Hydrogels for Local and Sustained Expression of Exogenous Proteins in Cells.

The application of synthetic messenger RNA (mRNA) exhibits various advantages, such as expression of desired proteins in cells without genomic integration. In the field of tissue engineering, synthetic mRNAs could be also used to modulate the protein expression in implanted cells. Therefore, in this study, we incorporated synthetic humanized Gaussia luciferase (hGLuc) mRNA into alginate, chitosan, or chitosan-alginate hybrid hydrogels and analyzed the release of hGLuc mRNA from these hydrogels. After 3 weeks, 79% of the incorporated mRNA was released from alginate hydrogels, approximately 42% was released from chitosan hydrogels, and about 70% was released from chitosan-alginate hydrogels. Due to the injectability, chitosan-alginate hybrid hydrogels were selected for further investigation of the bioactivity of embedded hGLuc mRNA and the stability of these hydrogels was examined after the incorporation of synthetic mRNA by rheometric analysis. Therefore, HEK293 cells were incorporated into chitosan-alginate hydrogels containing mRNA transfection complexes and the luciferase activity in the supernatants was detected for up to 3 weeks. These results showed that the biodegradable chitosan-alginate hybrid hydrogels are promising delivery systems for sustained delivery of synthetic mRNAs into cells. Since chitosan-alginate hybrid hydrogels are injectable, the hydrogels can be simultaneously loaded with cells and the desired synthetic mRNA for exogenous protein synthesis and can be administered by minimally invasive local injection for tissue engineering applications.

Combination of coating and injectable hydrogel depot to improve the sustained delivery of insulin

In this study, a sustained insulin delivery system was developed and evaluated with the combination of coating and injectable thermosensitive hydrogel depot. Poloxamer 407 (P407) and poloxamer 188 (P188) was employed as main materials and sodium alginate (SA) and hydroxypropyl methyl cellulose (HPMC) were incorporated to increase hydrogel strength. Insulin microcrystal was coated in a fluidized bed coater with a 2% (v/v)ethylcellulose (EC) solution. The hydrogels were characterized by scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FTIR). The gelation temperature and gelation time, syringeability and swelling were measured. Furthermore, the in vivo pharmacodynamic studies and muscular irritation were also evaluated. The results demonstrated that the hydrogels were biocompatible and combination of hydrogels with coated insulin microcrystal had optimum sustained release property for insulin.

Controlled biocide release from hierarchically-structured biogenic silica: surface chemistry to tune release rate and responsiveness

Biocides are essential for crop protection, packaging and several other biosystem applications. Therein, properties such as tailored and controlled release are paramount in the development of sustainable biocide delivery systems. We explore the self-similar nano-organized architecture of biogenic silica particles to achieve high biocide payload. The high surface area accessibility of the carrier allowed us to develop an efficient, low energy loading strategy, reaching significant dynamic loadings of up to 100 mg·g−1. The release rate and responsiveness were tuned by manipulating the interfaces, using either the native hydroxyl surfaces of the carrier or systems modified with amines or carboxylic acids in high density. We thoroughly evaluated the impact of the carrier-biocide interactions on the release rate as a function of pH, ionic strength and temperature. The amine and carboxyl functionalization strategy led to three-fold decrease in the release rate, while higher responsiveness against important agro-industrial variables. Key to our discoveries, nanostructuring thymol in the biogenic silica endowed systems with controlled, responsive release promoting remarkable, high and localized biocidal activity. The interfacial factors affecting related delivery were elucidated for an increased and localized biocidal activity, bringing a new light for the development of controlled release systems from porous materials.

Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues

The bio-engineering of nanoparticles for the transportation of various therapeutic agents specifically to brain has sparked a rapidly growing interest in the field of material chemistry. In this study, L-pGlu-(1-benzyl)–L-His–L-ProNH2 (NP-355) and L-pGlu-(2-propyl)–L-His–L-ProNH2 (NP-647) were synthesized and encapsulated in biodegradable poly-lactide-co-glycolide (PLGA) nanoparticles which were further decorated with mucoadhesive surface coating of chitosan. NP-355 and NP-647 which are analogues of thyrotropin releasing hormone, have been reported to demonstrate potential antiepileptic properties against various animal models of seizures. However, their applicability is limited by their short lives due to rapid metabolism and blood brain barrier. The treatment of disorders associated with central nervous system such as epilepsy has been a major challenge for several decades due to difficulty in delivery of drug molecules and imaging agents to brain. To overcome these issues, development of sustained release delivery system for these neuropeptides is proposed which can be administered directly from nose to brain utilizing olfactory nerve channels. The synthesized nanoparticles were evaluated for their physicochemical properties, sustained release properties, toxicity and antiepileptic potential following intranasal administration. The ability of these nanoparticles to reach the brain was evaluated by utilizing quantum dots as fluorescent probes. Our results proved that the polymeric nanoparticles can be used for successful delivery of neurological drugs to the brain.