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At the end of 80s and in the early 90s, an increasing interest in the development of mucoadhesive formulations occurred in the pharmaceutical field. Such formulations, prolonging the drug permanence on the mucosa of action/absorption, improve drug availability/bioavailability and therefore its therapeutic effectiveness. Among the various methods reported in the literature for the evaluation of the mucoadhesive properties of polymers, in the early 1990s, the study of the rheological variation of the polymer solutions after mixing with a mucin solution/dispersion has been proposed as an approach to measure the strength of the mucoadhesive joint. Even today, both viscosity and viscoelastic measurements are used to evaluate the ability of polymers and formulations to adhere to the mucosa of application/action. This review aims at providing an overview of the rheological approaches employed in the development and characterization of mucoadhesive formulation, highlighting their advantages and disadvantages. To do this the scientific path that, since the beginning of the 90s, has led to the affirmation of the rheological analysis as a useful tool for the evaluation of the strength of the mucoadhesive bond is retraced., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recently nanoparticle-based vaginal drug delivery formulations have been acquiring great attention for the administration of peptide based-vaccines or microbicides to prevent or treat sexually transmitted diseases. In this work, a straightforward and efficient strategy for the vaginal application and release of peptide-loaded mucoadhesive nanoparticles was developed. This essentially consists of chitosan nanoparticles encapsulated in suitable hydrophilic freeze-dried cylinders. Chitosan nanoparticles are responsible for carrying the peptide drug and allowing adhesion to the vaginal mucosal epithelium. Hydrophilic freeze-dried cylinders facilitate the application and quick release of the nanoparticles to the vaginal zone. Upon contact with the aqueous vaginal medium, the excipients constituting these sponge-like systems are quickly dissolved enabling the release of their content. In vitro release studies showed the ability of the sponge-like systems and chitosan nanoparticles to deliver the mucoadhesive nanoparticles and peptide respectively. CLSM micrographs proved the nanoparticles ability promoting the peptide penetration inside the vaginal mucosa., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.

Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked - (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: After more than four decades of intense research, oral controlled drug delivery systems (DDSs) still represent a topic of major interest for pharmaceutical scientist and formulators. This can be explained in part by considering the economic value of oral DDSs whose market accounts for more than half of the overall drug delivery market. Polymeric systems based on drug-polymer non-covalent interaction represent a limited, but growing part of the field. Despite the large amount of literature and published reviews covering specific aspects, there is still need for a review of the relevant literature providing a general picture of the topic., Areas Covered: The present review aims at presenting the latest findings in drug-polymer and interpolymer non-covalent interactions in oral controlled delivery while providing a specific perspective and a critical point of view, particularly on the tools and methods used for the study of these DDSs. Four main sections are considered: i) ionic interactions between drugs and polymers; ii) interpolymer complexes; iii) hydrogen bond; and iv) hydrophobic interactions., Expert Opinion: The largest part of the scientific literature deals with systems based on drug-polymer ionic interactions while hydrogen bonding and hydrophobic interaction though, very promising, are more difficult to exploit, and therefore less studied. An accurate and exhaustive representation of the specific role of the chemical functions in establishing predictable interactions between drug and polymers is still required.

The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP). The thiol groups of ThioPASP are able to form disulphide linkages with the mucin glycoproteins and prolong the residence time on the eye. The effects of the thiol groups on the structure, swelling behaviour and mucoadhesive character of the gel and on the drug release profile were determined. The gel structure was characterized by means of rheology. The ThioPASP gel was demonstrated by rheology, tensile test and 'wash away' measurements to display strong mucoadhesion. The drug release from the ThioPASP gel was studied on a vertical Franz diffusion cell: a burst release of sodium diclofenac occurred in the first hour, followed by sustained release of the encapsulated drug for up to 24h. The results proved the importance of the presence of the thiol groups and suggested that a ThioPASP formulation can be useful as an in situ gelling, ocular dosage form., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

Purpose: To determine the in vivo efficacy of cyclosporine A-loaded solid lipid nanoparticles (SLNs) in rabbit eyes., Methods: SLNs were prepared and administered to the cul-de-sac of rabbits, and the drug amount in aqueous humor was detected by high performance liquid chromatography (HPLC). The irritation was evaluated by modified Draize testing., Results: The particle size of SLNs was detected as 225.9 +/- 5.5 nm with a negative surface charge. Aqueous humor drug levels reached 50.53 ng/mL, and there was no serious irritation in rabbit eyes., Conclusions: Topical ophthalmic efficacy of cyclosporine A was enhanced via administration of SLNs.

This review considers the application of chitosan and its salts in the delivery of drugs intended to act locally towards diseases of the mucosa itself (mucosal delivery), and to undergo systemic absorption by means of transmucosal routes (transmucosal delivery). Those chitosan properties that are particularly useful in mucosal and transmucosal delivery have been reviewed, such as mucoadhesion, penetration enhancement and peptidase inhibition behaviour. Chitosan bioactive properties have also been considered, such as anti-infective, haemostatic, wound healing and immune-stimulating activity. Chitosan is available with a wide range of molecular mass and deacetylation degree: the influence of these properties on polymer performance and solubility has been taken into account. As solubility in particular can strongly limit the results obtained at pH values close to neutrality, particular attention has been paid to chitosan salts and derivatives with modified solubility. Thanks to the presence of positively charged amino groups of the polymer, a subject of increasing interest is the exploitation of its interaction with acidic molecules having potential synergistic behaviour towards bioactive properties, or even with acidic drugs. The aim of the review is to describe not only some properties of chitosan, but also the way they can be modified by the acidic moiety.

Aim of the work was to develop mucoadhesive eyedrops containing tetrahydrozoline hydrochloride (TZ), a decongestant drug, and based on a ternary interaction drug-polymer-polymer. The anionic polymers assessed were the anionic hyaluronic acid (HA) and polyacrylic acid (PAA), the cationic chitosan (HCS) and the polyelectrolyte gelatin (G). Formulations based on the ternary systems TZ/G/HA, TZ/HCS/HA, TZ/G/PAA and TZ/HCS/PAA at the stoichiometry ratios between cationic and anionic polymers and containing a 10 and 20 fold excess of the anionic polymers were prepared. The formulations were characterized for in vitro mucoadhesive and release properties. The ex vivo/in vivo residence properties were assessed for the formulations that combined the better in vitro mucoadhesive and release properties. The physical stability of the formulations selected was determined following steam sterilization and storage at 25 and 40 degrees C. The synergistic effect of G with HA and PAA improves the mucoadhesion of the formulations while the interaction of HCS with HA and PAA is likely to produce higher neutralization of the anionic polymer charge and minor chain flexibility resulting in a limited mucoadhesion improvement. Both G and HCS participate to control drug release. The selected formulations demonstrate to possess consistency (viscosity) sensitive to the ions of the medium, and probably for this reason the ex vivo/in vivo residence properties could not directly correlated to mucoadhesion and to drug release control properties. However, the formulations are able to maintain levels of TZ detectable until 20 min after the instillation in rabbits, while TZ was not detectable since 3 min after instillation of the drug solution. The physical stability, following steam sterilization and storage, the low viscosity combined with good residence time in conjunctival sac make the TZ/G/20HA the more promising formulation.

Lambda-carrageenan is an anionic polymer able to ionically interact with alkaline drugs. This results in a complex that releases the drug slowly, due to displacement by the counterions of the release medium. The aim of this work was to assess the possible ophthalmic employment of such a complex. As a model drug, an alkaline anti-glaucoma drug, timolol maleate, was chosen. Systems in which lambda-carrageenan interacted both with the drug and a mucoadhesive polymer such as gelatin were studied. The combination of carrageenan and gelatin in different ratios proved to be useful in modulating the drug release profiles, the rheological properties of the hydrated formulations and their mucoadhesive properties. Both films and microspheres were prepared and tested in vitro. A microsphere formulation was also tested in vivo in albino rabbits. The drug concentration and bioavailability in the aqueous humour were significantly high in comparison with commercial formulations.

The complex pathophysiology of spinal cord injury (SCI) may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. A primary mechanical injury in the spinal cord triggers a cascade of secondary events, which are involved in SCI instauration and progression. The aim of the present review is to provide an overview of the therapeutic neuro-protective and neuro-regenerative approaches, which involve the use of nanofibers as local drug delivery systems. Drugs released by nanofibers aim at preventing the cascade of secondary damage (neuro-protection), whereas nanofibrous structures are intended to re-establish neuronal connectivity through axonal sprouting (neuro-regeneration) promotion, in order to achieve a rapid functional recovery of spinal cord. [ABSTRACT FROM AUTHOR]

Ocular drug delivery formulations must meet anatomical, biopharmaceutical, patient-driven and regulatory requirements. Mucoadhesive polymers can serve as a better alternative to currently available ophthalmic formulations by providing improved bioavailability. If all requirements are addressed, a polymeric formulation resembling the tear film of the eye might be the best solution. The optimum formulation must not have high osmotic activity, should provide appropriate surface tension, pH and refractive index, must be non-toxic and should be transparent and mucoadhesive. We would like to highlight the importance ofin vitropolymer testing from a pharmaceutical aspect. We, therefore, carried out physical–chemical investigations to verify the suitability of certain systems for ophthalmic formulations. In this work,in situgelling, mucoadhesive thiolated poly(aspartic acid)s were tested from ophthalmic formulation aspects. The results of preformulation measurements indicate that these polymers can be used as potential carriers in ophthalmic drug delivery. [ABSTRACT FROM PUBLISHER]

The aim of the present work was the development of vaginal sponge-like dressings based on chitosan ascorbate (CS) and on hyaluronic acid sodium salt/lysine acetate (HAS) combination. Sponge-like dressings were prepared by freeze-drying and characterized for mechanical resistance and mucoadhesion. CS dressings show higher mechanical and mucoadhesion properties in comparison with HAS dressing. The enzymatic inhibition properties of the dressings were evaluated in vitro against carboxipeptidase A in view of their employment for vaginal delivery of peptidic drugs. All the dressings were able to inhibit carboxipeptidase activity; CS dressings, independently of polymer MW, completely inhibited enzyme activity. Release and penetration enhancement properties of the dressings loaded with a high molecular weight hydrophilic molecule, fluorescein isothiocyanate dextran (FD4), were assessed. CS dressings were able to prolong FD4 release. All the dressings showed penetration enhancement properties into pig vaginal mucosa although to a different extent: greater for dressings based on CS than for that containing HAS. Moreover, CS dressings demonstrated intrinsic antimicrobial properties. The suitability of sponge-like systems for the treatment of vaginal infections was assessed by loading the CS dressing characterized by the best mechanical and antimicrobial properties with an antibiotic drug (clyndamicin-2-phosphate) and by checking drug release. [ABSTRACT FROM AUTHOR]

The aim of the present work was to investigate the capability of vancomycin (VCM) to interact with three hydrophobic cyclodextrins (TACD) (triacetyl alfa-, beta-, or gamma cyclodextrin) and the role played by the preparation technique in the formation of interaction products aimed at prolonging drug delivery for site-specific treatment of bone infections. Physical mixtures of VCM with triacetyl α-, β-, or γ-cyclodextrin in a 1:1 molar ratio were subjected to kneading, coevaporation, and spray drying from aqueous suspensions or hydroacetonic solution. Thermal behavior (TG, DSC), percent drug content (HPLC), and drug release (Franz cell) of VCM from the physical mixtures, and the relevant binary systems obtained by the various complexation methods were evaluated. All binary systems were characterized by having a particle size compatible with parenteral site-specific administration and with drug-loading efficiencies close to 100%, thus indicating the stability of vancomycin toward each and every complexation process. In vitro drug release measurements showed that the preparation technique plays a different role depending on the type of cyclodextrin used. In the kneading process, the binary system containing TAαCD is the most efficient in slowing down the VCM release. With the coevaporation technique, the system based on TAβCD was most effective in prolonging drug release. None of the triacetyl-cyclodextrins is suitable in prolonging VCM release upon spray drying from aqueous suspensions, because this preparation technique does not determine drug-cyclodextrin interaction. On the other hand, spray drying from hydroacetonic solutions always results in a reduction in drug release, linked to the formation of VCM-TACD interaction products and is particularly pronounced for the VCM-TAγCD interaction product. The unique properties of prolonging drug release and maintaining the antimicrobial activity of the native drug render such an interaction product the most promising candidate in the development of delivery systems intended for parenteral site-specific administration of VCM. [ABSTRACT FROM AUTHOR]

The oral fast-dissolving systems are defined as oral drug delivery systems that dissolve or disintegrate within a few seconds to a few minutes of placement in the mouth and that do not require water to aid swallowing. Various technologies are used to achieve quick dissolution/dispersion in the oral cavity. This review focuses on the properties of the various fast-dissolving (orally disintegrating) technologies for systemic drug delivery. Freeze-drying, molding, and compaction technologies are described. Zydis®, Quicksolv® and Lyoc® are prepared by freeze drying; FlashDose® is prepared by a molding/cotton-candy process; WOWTAB®, FlashTab® and Frosta? are prepared by granulation followed by compression; OraSolv®, DuraSolv®, Ora Vescent®, QDis®, Ziplets® and AdvaTab® are prepared by direct compression. Differences between drug delivery systems with regard to their composition (excipients), structure and formulation are also reviewed. Employment of relatively consolidated technologies (lyophilization, compaction, and granulation) can shorten the formulation, development, and scaling-up processes. In addition, the properties of systems prepared using these technologies are critically compared. The advantages and the disadvantages of each type of dosage form in terms of dissolution and absorption rate, bioavailability, stability, mechanical strength, taste-masking properties, and patient compliance are emphasized. The implications of these differences for patient compliance and choice of technologies in drug formulation are highlighted. Freeze-drying allows immediate dissolution of the tablets because of their high porosity, and enhances drug stability, especially for moisture-sensitive substances; on the other hand, a porous network is associated with low physical resistance and high friability, and special packaging is required in some cases. Use of the molding technology results in tablets with an appropriate dissolution time, even though they are characterized by poor mechanical properties (hardness). The fast-dissolving tablets based on compaction technologies utilize consolidated technologies (standard equipment and materials) and their production costs are low. Most of these tablets are characterized by good physical resistance (hardness), although this can result in an increase in the disintegration time. Apart from its favorable anatomic and physiologic features that allow modulation of drug permeation, the high degree of vascularization, minimal enzymatic pool and potential to avoid first-pass metabolism make the oral cavity an ideal site for peptide/protein delivery and absorption using fast-dissolving formulations. Furthermore, the gentle preparation procedures and technologies (in particular lyophilization) used in the manufacture of oral fast-dissolving tablets are compatible with the delicate drug substances delivered by these formulations. [ABSTRACT FROM AUTHOR]

This review aims to illustrate the potential of the buccal route for delivery of peptide drugs. Compared with the oral, nasal, and rectal routes for drug delivery, the buccal route presents advantages such as an efficient blood supply and relatively low enzymatic activity. Moreover, the buccal mucosa is easily accessible and acceptable to patients; it allows the patient to interrupt drug administration by simply removing the drug delivery system. On the other hand, the buccal route is characterized by some intrinsic limitations (barrier properties of the mucosa, small area available for drug absorption, short residence time of the formulation caused by physiologic-removal mechanisms), which have to be considered in the design of buccal drug delivery systems. After a description of the relevant anatomic and physiologic features of the buccal mucosa and of the factors affecting mucosal absorption, strategies adopted to promote the buccal absorption of peptides are discussed. In particular, recent developments in formulation design are presented. Attention is focused on the employment of penetration enhancers, enzyme inhibitors, and mucoadhesive agents as functional excipients in buccal formulations. Currently, research is oriented towards the design of new materials combining all of these latter properties. In the last few years some chitosan derivatives have been proven to fulfil such requirements. Different formulations have been studied: gels, tablets, and films. Recently a novel liquid aerosol formulation of insulin has been developed and it is now in clinical phase II trials. [ABSTRACT FROM AUTHOR]

The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheological and turbidimetric analysis. Films containing 1 mg/cm2 of acyclovir and based on pure HCS and on HCS and PAA mixed in different ratios were prepared by casting technique. The films were subjected to hydration, rheological, mucoadhesion, drug release, “wash away,” and permeation/penetration measurements. A commercial cream containing acyclovir and an aqueous acyclovir suspension were used as references. The addition of PAA to HCS produced a decrease in film hydration. Films based on HCS/PAA weight ratio close to interaction product stoichiometry were characterized by higher rigidity and better “wash away” properties with respect to the other films and the reference formulation. The worst mucoadhesive properties were shown by films based on mixing ratios close to interaction product stoichiometry. The addition of PAA to HCS produced a lowering in drug release profile. All the films examined promoted the permeation of acyclovir across porcine cheek epithelium when compared with acyclovir suspension and the commercial cream. The penetration enhancement properties were affected by the mixing ratio of the two polymers. The film based on 1/1.3 HCS/PAA weight ratio, besides possessing the best resilience properties on the mucosa, was also characterized by the highest permeation profile and, therefore, represents a promising formulation for buccal delivery of acyclovir. [ABSTRACT FROM AUTHOR]

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies. [ABSTRACT FROM AUTHOR]

Thiolated polymers are a promising new group of excipients, but their stability against atmospheric oxidation has not been investigated in detail, and only a few efforts have been made to improve their stability. The oxidation of the thiol groups in solutions of thiolated polymers may result in a decrease of mucoadhesion and unpredictable in situ gelation. The aims of our work were to study the stability of aqueous solutions of thiolated polymers and the effects of stabilizing agents. We investigated thiolated poly(aspartic acid) polymers stabilized with dithiothreitol, glutathione or acetylcysteine. The effects of these antioxidants on the gel structure, mucoadhesion and drug release were determined by means of scanning electron microscopy, swelling, rheology, adhesion and drug release tests. It was concluded that the stability of polymer solutions containing antioxidants is sufficient for one day. Polymers stabilized with dithiotreitol demonstrated fast swelling and drug release, but weaker mucoadhesion as compared with the other samples. Polymers stabilized with glutathione displayed the weakest cohesive properties, resulting in fast and uncontrolled drug release and moderate mucoadhesion. Acetylcysteine-stabilized polymers exhibited an optimum cross-linked structure, with free thiol groups ensuring polymer-mucin interactions, resulting in the best mucoadhesive properties. [ABSTRACT FROM AUTHOR]

Solid Lipid Nanoparticles (SLNs) composed of biodegradable physiological lipids have been widely proposed as efficient drug delivery systems, also for ophthalmic administration. Recently, chitosan-associated-SLNs have been developed to further improve the residence time of these colloidal systems in the precorneal area by means of mucoadhesive interaction. In the present study, a one-step preparation protocol was used aiming both at scale-up ease and at stronger coupling between chitosan and SLNs. The resulting particles were chitosan associated-SLNs (CS-SLNs). These nanoparticles were characterized, as compared to both the chitosan-free and the usual chitosan-coated ones, by applying a multi-technique approach: light, neutron and X-ray scattering, Zeta-potential, AFM, calorimetry. It was assessed that, while keeping the features of nano-size and surface-charge required for an efficient vector, these new nanoparticles display a strong and intimate interaction between chitosan and SLNs, far more settled than the usual simple coverage. Moreover, this one-step preparation method allows to obtain a strong and intimate interaction between chitosan and SLNs, firmer than the usual simple coating. This confers to the CS-SLNs an improved mucoadhesion, opening the way for a high-performing ophthalmic formulation. [ABSTRACT FROM AUTHOR]

The aim of the present work was the development of a powder formulation for the delivery of manuka honey (MH) bioactive components and platelet lysate (PL) in chronic skin ulcers. In particular pectin (PEC)/chitosan (CS) particles were prepared by ionotropic gelation in the presence of calcium chloride and subsequently characterized for particle size, hydration properties and mechanical resistance. Different experimental conditions (calcium chloride and CS concentrations; rest time in the cationic solution) were considered in order to obtain particles characterized by optimal size, hydration properties and mechanical resistance. Two different fractions of MH were examined: one (Fr1), rich in methylglyoxal and the other (Fr2), rich in polyphenols. Particles were loaded with Fr1, fraction able to enhance in vitro proliferation of human fibroblasts, and with PL. The presence of CS in Fr1-loaded particles produced an improvement in cell proliferation. Moreover, PL loading into particles did not affect the biological activity of the hemoderivative. In vivo efficacy of PL- and Fr1-loaded particles was evaluated on a rat wound model. Both treatments markedly increased wound healing to the same extent. [ABSTRACT FROM AUTHOR]

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue’s integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro . The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present work was the development of a powder formulation for the combined delivery of platelet lysate and of a model antibiotic drug, vancomycin hydrochloride (VCM), in chronic skin ulcers. Calcium alginate particles were prepared by freeze-drying beads obtained by ionic gelation method. The experimental conditions adopted permitted the complete loading of VCM and of PDGF AB, the growth factor chosen as representative of those contained in PL. Such particles where able to absorb PBS (mimicking wound exudate), to form a gel and to modulate the release of VCM and of PDGF AB. They are characterized by enhancement properties of human fibroblast proliferation due to PL presence. In particular, PL, when loaded in alginate particles, was able not only to increase the number of viable cells, but also the number of cells in proliferative phase. Such properties were comparable to those of fresh PL indicating the capability of calcium alginate particles to load PL bioactive substances without altering their activity. The formulation developed is characterized by an easier and a less painful administration with respect to traditional gauzes and semisolid preparations and permits the loading in the same dosage form of active substances of different nature avoiding eventual incompatibility problems. [Copyright &y& Elsevier]

Abstract: Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds. [Copyright &y& Elsevier]

Abstract: A “Clay Bio Polymer Nanocomposite” (CBPN) to be used in drug release was prepared by dispersion of montmorillonite (Mt) particles in chitosan (Ch) solution. The obtained hybrid material was characterized for in vitro biocompatibility on Caco-2 cell cultures. Cytotoxicity and cell proliferation of the nanocomposite were tested, comparing results with free Ch and Mt. Cell proliferation was assessed both by WST-1 test and wound-healing measurements by means of Image Analysis Software. The last method is a proof of concept test that has the advantage of direct visualization and quantification of cell growth. Nanocomposite was also characterized for hydration (water uptake) pattern and mucoadhesive properties, which were considered as important features for the application of this material in modified release systems. Results showed that the prepared CBPN showed good biocompatibility in the range 5–500μg/ml, being also able to effectively stimulate cell proliferation. Moreover, nanocomposite possessed mucoadhesive properties combined with low solubility in acidic environment. We conclude that interaction between Ch and Mt produced a new biohybrid material that can be considered as promising candidate for modified drug delivery formulations. [Copyright &y& Elsevier]