Design and development of novel bioadhesive niosomal formulation for the transcorneal delivery of anti-infective agent:In-vitro and ex-vivo investigations

Gatifloxacin eye drops are frequently used in eye infections.However such formulations have a major drawback i.e.short duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency.Vesicles were prepared by solvent injection method using cholesterol and Span-60.An extensive optimization of formulation was done using different ratios of cholesterol,Span-60 and drug,revealed NS60-5(cholesterol:span-6050:50 and drug content of 20 mg)to be the optimized niosome formulation.NS60-5 had shown a highest entrapment efficiency of 64.9±0.66%with particle size 213.2±1.5 nm and zeta potential
34.7±2.2 mV.Optimized niosomes were also coated with different concentrations of chitosan and evaluated.Permeation studies had revealed that optimized niosomes(86.77±1.31%)had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution(37.19±1.1%).Longer retention potential of the coated niosomes was further verified by fluorescence microscopy.Study revealed that simple dye solution got easily washed out with in 6 h.The uncoated niosomes(NS60-5)showed a longer retention(more than 6 h),which was further enhanced in case of coated niosomes i.e.CNS60-1(more than 12 h).Antimicrobial studies had shown the better efficacy of CNS60-1(zone of inhibition)when compared to marketed formulation.The final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations.

The development of polycarbophil as a bioadhesive material in pharmacy

Polycarbophil(PCP),a kind of pharmaceutical polymers with superior bioadhesive properties has been widely used in the field of controlled drug delivery systems.It could be used as a highly efficient thickener,bioadhesive agent,suspending aid and emulsion stabilizer when dispersed in water or other polar solvents.These exceptional utilities of the polymers result from their hydrophilic nature.Hydrogen bonding plays an important role in most adhesion behaviours and becomes the main adhesion force.This paper reviews the applications of PCP in pharmacy over the past decades,and clarifies its unique advantages in the bioadhesive formulations.After an introduction discussing its structural characteristics and action mechanism,the focus turned to the description of its available applications in detail with particular emphasis on the ocular,nasal,vagina and oral drug delivery systems.The other less developed formulations are also described,including the buccal and the transdermal delivery systems.

Enhancing the separation performance by introducing bioadhesive bonding layer in composite pervaporation membranes for ethanol dehydration

A high performance composite membrane was prepared under the inspiration of bioadhesion principles for pervaporative dehydration of ethanol.Chitosan(CS)and polyacrylonitrile(PAN)ultrafiltration membranes were used as the active layer and the support layer,respectively.Guar gum(GG),a natural bioadhesive,was introduced as the intermediate bonding layer to improve the separation performance and stability of the fabricated CS/GG/PAN composite membranes.The contact angle of the GG layer was just between those of the CS layer and the PAN layer,minimizing the difference of hydrophilicity between the active layer and the support layer.The peeling strength of the composite membrane was significantly enhanced after the introduction of the GG layer.The effects of preparation conditions and operation conditions including GG concentration,operating temperature and ethanol concentration in feed on the pervaporation performance were investigated.The as-fabricated CS/GG/PAN composite membrane showed the optimum performance with a permeation flux of up to804 g·m-2·h-1and a separation factor higher than 1900.Besides,the composite membranes exhibited a desirable long-term operational stability.

Isoreactive Manipulation of Bioadhesive Polymers Impacts Tissue-Specific Interactions

Bioadhesive polymers can serve as surgical sealants with a wide range of potential clinical applications, including augmentation of wound closure and acute induction of hemostasis. Key determinants of sealant efficacy include the strength and duration of tissue-material adhesion, as well as material biocompatibility. Canonical bioadhesive materials, however, are limited by a tradeoff among performance criteria that is largely governed by the efficiency of tissue-material interactions. In general, increasingly bioreactive materials are endowed with greater bioadhesive potential and protracted residence time, but incite more tissue damage and localized inflammation. One emergent strategy to improve sealant clinical performance is application-specific material design, with the goal of leveraging both local soft tissue surface chemistry and environmental factors to promote adhesive tissue-material interactions. We hypothesize that copolymer systems with equivalent bioreactive group densities (isoreactive) but different amounts/oxidation states of constituent polymers will exhibit differential interactions across soft tissue types. We synthesized an isoreactive family of aldehyde-mediated co-polymers, and subjected these materials to physical (gelation time), mechanical (bulk modulus and adhesion strength), and biological (in-vitro cytotoxicity and in-vivo biocompatibility) assays indicative of sealant performance. Results show that while bioadhesion to a range of soft tissue surfaces (porcine aortic adventitia, renal artery adventitia, renal cortex, and pericardium) varies with isoreactive manipulation, general indicators of material biocompatibility remain constant. Together these findings suggest that isore-active tuning of polymeric systems is a promising strategy to circumvent current challenges in surgical sealant applications.

Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.

An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration

Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel that possesses rapid gelation,firm tissue adhesion,high mechanical strength,suitable degradability,and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets.Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy,wound closure,alveolar ridge preservation,and in situ alveolar bone regeneration.Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation,elevated collagen deposition,higher osteoblast activity,and enhanced angiogenesis.Together,our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.

Smart bioadhesives for wound healing and closure

The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion,antibacterial effect,real-time sensing,wireless communication,and on-demand treatment capabilities.Bioadhesives with bio-inspired structures and chemicals have shown unprecedented adhesion strengths,as well as tunable optical,electrical,and bio-dissolvable properties.Accelerated wound healing has been achieved via directly released antibacterial and growth factors,material or drug-induced host immune responses,and delivery of curative cells.Most recently,the integration of biosensing and treatment modules with wireless units in a closed-loop system yielded smart bioadhesives,allowing real-time sensing of the physiological conditions(e.g.,pH,temperature,uric acid,glucose,and cytokine)with iterative feedback for drastically enhanced,stage-specific wound healing by triggering drug delivery and treatment to avoid infection or prolonged inflammation.Despite rapid advances in the burgeoning field,challenges still exist in the design and fabrication of integrated systems,particularly for chronic wounds,presenting significant opportunities for the future development of next-generation smart materials and systems.

Hydrogel bioadhesives harnessing nanoscale phase separation for Achilles tendon repairing

Repairing Achilles tendon has emerged as a long-standing challenge in the orthopaedic surgeries.Although suture is the gold standard for re-attaching and repairing the fractured Achilles tendons in clinical surgeries,it is still subjected to numerous adverse side-effects,including chronic inflammatory,tendon tissue re-rupture,scar formation,and post-surgical peritendinous adhesion.In this work,we develop a class of hydrogel bioadhesives with tailored nanoscale phase separation for Achilles tendon repairing.To address the existing limitations of sutures,our hydrogel bioadhesives encompass three core functionalities:(i)instant and tough adhesion to Achilles tendon tissues,(ii)extraordinary long-term adhesion robustness under wet and dynamic in vivo conditions,and(iii)anti-postsurgical peritendinous adhesion.Combining our hydrogel bioadhesives with sutures,such kind of integrated approach enables a conformable yet robust biointerface with the tendon tissues,and prevents the fibroblast migration and formation of connective tissues,thus facilitating the tendon repairing.The hydrogel bioadhesives reported here open up new opportunities for the repairing of fractured Achilles tendons in diverse and complicated clinical scenarios.

A“T.E.S.T.”hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.

In situ Injectable Tetra-PEG Hydrogel Bioadhesive for Sutureless Repair of Gastrointestinal Perforation

Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow and/or weak adhesive,poor mechanical strength,low biocompatibility,and poor biodegradability,which largely limit their clinical application in GI perforation repair.In this work,we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive(SS)composed of tetra-armed poly(ethylene glycol)amine(Tetra-PEG-NH2)and tetra-armed poly(ethylene glycol)succinimidyl succinate(Tetra-PEG-SS)for the sutureless repair of GI defects.The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models.Importantly,the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation.The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion,suppressed inflammation,and enhanced angiogenesis.Together,our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.

Effect of bioadhesive excipients on absorption of total flavonids from Puerariae Lobatae Radix transporting across Caco-2 cell monolayer

Objective: Pueraria total flavonids(PTF) can treat cardiovascular and cerebrovascular diseases, but it has poor membrane permeability and oral bioavailability. Some excipients, such as carbomer, chitosan, and hydroxypropyl methylcellulose, can improve the oral bioavailability. Traditional in vitro evaluation techniques, including the rat intestinal perfusion and cell line models, cannot evaluate PTF absorption and holistic transporters.Methods: This study evaluated excipients' adhesiveness and effect on PTF transport across Caco-2 cell monolayer. cDNA microarrays identified gene expression changes in Caco-2 cells exposed to PTF and PTF with excipients, and revealed the mechanism underlying the effect of excipients on PTF absorption.Results: In vitro adhesion and transport experiments across Caco-2 showed that excipients had higher adhesiveness to gastric mucosa and transport efficiency across Caco-2 cells than PTF alone. The interaction of PTF with excipients significantly changed the expression of some genes, which might influence the absorption rate of PTF.Conclusion: Different bioadhesive polymers can improve intestinal absorption of PTF, which was related to some genes affiliated to the ATP-binding cassette(ABC) and solute carrier transporter(SLC) to some extent.

Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty

Keratoplasty is the gold standard treatment for visual impairment caused by corneal damage.The use of suturing as the bonding method is the source of many complications following keratoplasty.Currently available corneal adhesives do not have both adequate adhesive strength and acceptable biocompatibility.Herein,we developed a photocurable bioadhesive hydrogel which was composed of gelatin methacryloyl and oxidized dextran for sutureless keratoplasty.The bioadhesive hydrogel exhibited high light transmittance,resistance to enzymatic degradation and excellent biocompatibility.It also had higher adhesive strength than commercial adhesives(fibrin glue).In a rabbit model of lamellar keratoplasty,donor corneal grafts could be closely bonded to the recipient corneal bed and remained attached for 56 days by using of this in situ photopolymerized bioadhesive hydrogel.The operated cornea maintained transparent and noninflamed.Sutureless keratoplasty using bioadhesive hydrogel allowed rapid graft re-epithelialization,typically within 7 days.In vivo confocal microscopic and histological evaluation of the operated cornea did not show any apparent abnormalities in terms of corneal cells and ultrastructure.Thus,this bioadhesive hydrogel is exhibited to be an appealing alternative to sutures for keratoplasty and other corneal surgeries.

Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications

Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility,easy processability,transparency,non-toxicity,and reasonable mechanical properties to mimic the extracellular matrix(ECM).Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application.We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor,utilizing epoxide ring-opening reactions and visible light-crosslinking.This chemical modification allows the obtaining of an elastic protein-based hydrogel(GELGYM)with excellent biomimetic properties,approaching those of the native tissue.GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80%compared to Gelatin-methacryloyl(GeIMA),the most studied derivative of gelatin used as a bioadhesive.GELGYM is also highly biocompatible and supports cellular adhesion,proliferation,and migration in both 2 and 3-dimensional cell-cultures.These characteristics along with its super adhesion to biological tissues such as cornea,aorta,heart,muscle,kidney,liver,and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation,tissue adhesive,wound dressing,bioprinting,and drug and cell delivery.

Cohesion mechanisms for bioadhesives

Due to the nature of non-invasive wound closure,the ability to close different forms of leaks,and the potential to immobilize various devices,bioadhesives are altering clinical practices.As one of the vital factors,bioadhesives’strength is determined by adhesion and cohesion mechanisms.As well as being essential for adhesion strength,the cohesion mechanism also influences their bulk functions and the way the adhesives can be applied.Although there are many published reports on various adhesion mechanisms,cohesion mechanisms have rarely been addressed.In this review,we have summarized the most used cohesion mechanisms.Furthermore,the relationship of cohesion strategies and adhesion strategies has been discussed,including employing the same functional groups harnessed for adhesion,using combinational approaches,and exploiting different strategies for cohesion mechanism.By providing a comprehensive insight into cohesion strategies,the paper has been integrated to offer a roadmap to facilitate the commercialization of bioadhesives.

Engineering multifunctional bioadhesive powders through dynamic metal-ligand coordination

Bioadhesive gels with robust adhesion on wet and irregular tissue surfaces are desirable for clinical applications.Assembly of bioadhesive powders is an effective strategy for obtaining gels that adhere to wet and irregular tissue surfaces by absorbing interfacial water.However,current bioadhesive powders lack positive biological functions and are prone to postoperative adhesion.Here,we present a powder strategy based on metal-ligand coordination to create a series of bioadhesive polyacrylic acid(PAA)gels.In the gel network,metal ions(M^(n+))are used to coordinate with the carboxy ligands of PAA to form dynamic noncovalent crosslinks.The powders can absorb interfacial water and assemble into gels on wet and irregular tissue surfaces within a few seconds,forming an initial adhesion layer by electrostatic interactions.Furthermore,the polymers can diffuse into the tissue matrix,and metal-ligand coordination is reconstructed to enhance the adhesion.Moreover,with a cationic shield layer,the bioadhesive powders can effectively avoid postoperative adhesion.Importantly,M^(n+) ions endow the gel with customized biological functions.We demonstrate that the hemostatic,antibacterial,peroxidase-like catalytic,and photodetachment abilities of the gels by incorporating different M^(n+) ions.These advantages make the bioadhesive powder a promising platform for diverse tissue repair applications.

Adhesive cryogel particles for bridging confined and irregular tissue defects

Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging.Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies,making tissue bridging challenging.Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles(ACPs) made from chitosan,acrylic acid,1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC) and N-hydroxysuccinimide(NHS).The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart,intestine,liver,muscle,and stomach.Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells(LO2)and human intestinal epithelial cells(Caco-2).The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models.The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart,liver,and kidney as the ex vivo models.Furthermore,a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness,biocompatibility,and applicability in clinical surgery.Results ACPs are applicable to confined and irregular tissue defects,such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs.ACPs formed tough adhesion between tissues[(670.9±50.1) J/m^(2) for the heart,(607.6±30.0) J/m^(2) for the intestine,(473.7±37.0) J/m^(2) for the liver,(186.1±13.3) J/m^(2) for the muscle,and(579.3±32.3) J/m^(2) for the stomach].ACPs showed considerable cytocompatibility in vitro study,with a high level of cell viability for 3 d[(98.8±1.2)%for LO2 and(98.3±1.6)%for Caco-2].It has comparable inflammation repair in a ruptured rat liver(P=0.58 compared with suture closure),the same with intestinal anastomosis in rabbits(P=0.40 compared with suture anastomosis).Additionally,ACP-based intestinal anastomosis(less than 30 s) was remarkably faster than the conventional suturing process(more than 10 min).When ACPs degrade after surgery,the tissues heal across the adhesion interface.Conclusions ACPs are promising as the adhesive for clinical operations and battlefield rescue,with the capability to bridge irregular tissue defects rapidly.

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.

Chitosan:Vitamin C Containing Hydrogels as a Prototype Functional Prolonged Pain Management Restorative Material <i>In-Vitro</i>Studies

Restorative materials in the new era aim to be “bio-active” and long-lasting. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and wound healing, we design and evaluate several novel chitosan-vitamin C (5:1) containing hydrogels as a prototype of host:guest molecular free radical defense material containing hydroethanoic propolis extract (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), or aspirin (pain relieve medication and free radical scavengers) as functional restorative materials. We will evaluate the physical properties, bonding to dentin as well as test the bioadhesion of the newly designed materials in order to access the suitability of these prototype materials as suitable restorative materials. Materials and Methods: The hydrogels were prepared by previously reported by us protocol. The physico-chemical features including surface morphology (SEM), release behaviors, stability of the therapeutic agent-anti-oxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel were reported. Bio-adhesive studies were performed in order to assess the suitability of these designed materials. Results: Release of aspirin, ibuprofen and naproxen conferred the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Either the release of therapeutic agents or the antioxidant stability was affected by storage over a 12-month period. All chitosan:vitamin C hydrogels showed gave significantly higher shear bond values than dentin treated or not treated with phosphoric acid, which highlighted the feasibility. The bio-adhesive capacity of the materials in the 2 separate “in vitro” systems were tested and quantified. Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favourable synergistic effect of free radical build-in defense mechanism of the new functional materials. Conclusion: Additional action of chitosan:vitamin C pre-complex was investigated and it was found that favorable synergistic effect of free radical build-in defense mechanism of the new functional materials, increased dentin bond strength, sustainable bio-adhesion, and acted as a “proof of concept” for the functional multi-dimensional restorative materials with potential application in wound healing in vitro.

Development and Characterisation of Natamycin Mini-Matrices Prepared by Hot-Melt Extrusion for Vaginal Delivery

In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.

Evaluation Preliminary of a Dry Emulsion System as a <i>Pasteurella multocida</i>Oral Carrier for Pigs

Background: This work evaluated the capacity of a dry emulsion as a carrier of viable microorganisms with potential use as prophylaxis of infectious diseases. Methods: The aqueous phase containing P. multocida not viable in PBS was emulsified in mineral oil to obtain a w/o emulsion. The microorganisms remained stable and only in two cases (n = 6) did the bacterial concentration decrease. Scanning Electron Microscopy (SEM) revealed a structure of a system with the organized association of particles with cubic symmetry. Using two ex vivo bioadhesion systems, it was demonstrated that the disperse-adsorbed system is capable of adhering to the intestinal mucosa and remains adhered for long periods of time. Results: The no viability of the bacteria in the dry emulsion and the possibility of controlled release were confirmed. In vivo trial was conducted in pigs. It was possible to locate the emulsion and the bacteria attached to the gut of the living animal. An ELISA kit was used to monitor the mean antibody titer of treated pigs over a 2-week period, and a classic primary response curve occurred when the titer was plotted against time. Conclusion: We propose the disperse-adsorbed system as an alternative to commonly used vehicles for immunogens in the oral vaccines.