Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Poly(Vinyl Alcohol) Cryogel Membranes Loaded with Resveratrol as Potential Active Wound Dressings.

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.

In vivo safety assessment, biodistribution and toxicology of polyvinyl alcohol microneedles with 160-day uninterruptedly applications in mice.

Dissolving microneedles (DMNs) are widely used in drug delivery systems since they are based on one-step application, which is simple and convenient for patients, especially for the patients such as diabetes who need daily or long-term self-administration. In general, the matrix materials of DMNs are water-soluble materials that can release the encapsulated drugs gradually by dissolving in the skin without generating sharp needle waste. However, the matrix materials of DMNs will also leave in the skin after application. Thus, it is vital to evaluate whether the matrix material of DMNs dissolved in the skin will cause health risks such as toxicity to the body or some skin-related complications to patients who frequent or long-term administration. In this work, PVA, as one of the typical matrix materials of DMNs, was selected to prepare the DMNs to research the safety of PVA-based MNs to the body after being dissolved in the skin. Briefly, in a 160 - days trial, the healthy mice were daily administrated by PVA MNs. The results showed that PVA materials mainly accumulated in the skin tissues of mice after dissolving and the concentration of PVA in the insertion sites gradually decreased and was almost undetectable at 6 days after administration. The observation of general conditions, blood hematological analysis and histological examinations of the mice demonstrated that the PVA-based MNs do not cause appreciable toxicity to the healthy mice after daily insertion in a 160 - days trial. Altogether, these results encourage further studies of PVA MNs for biomedical applications and support translation of PVA-based DMNs from pre-clinical development into clinical trials.

In vivo microscopy of arterial distribution embolic particles in rabbit mesenteric artery.

PURPOSE: To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy.To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy. METHODS: Sixteen New Zealand rabbits were divided into four groups, namely large PVA (560-710 µm), small PVA (150-350 µm), large EM (500-700 µm), and small EM (100-300 µm). The mesenteric arteries of the experimental animals were embolized under fluoroscopic guidance and visualized using in vivo microscopy. The embolized vessel diameter and arterial distribution of embolic agents were compared. RESULTS: The diameters of occluded vessels in large PVA, small PVA, large EM, and small EM groups were 430.60 ± 67.30, 200.95 ± 70.54, 387.79 ± 92.51, and 143.81 ± 39.65 µm, respectively. PVA occluded significantly larger vessels than EM when the particle size was similar (P < 0.001). The proportion of EM at the bifurcation of the artery was significantly higher than that of PVA particles (large PVA < large EM, χ2 = 4.325, P < 0.038; small PVA < small EM, χ2 = 6.68, P < 0.01). CONCLUSION: Both PVA and EM could occlude vessels smaller than the particle size, and EM resulted in deeper penetration. The location of embolic particles in the artery is mainly related to the shape of particles.

Preparation and release properties of arbutin imprinted inulin/polyvinyl alcohol biomaterials.

The main objective of this work was to prepare inulin (INL)/polyvinyl alcohol (PVA) biomaterials imprinted with arbutin (AR) as the target drug. INL from Jerusalem artichoke flour was extracted with hot water extraction method. INL/PVA biomaterials were synthesized with a casting method and a UV curing. The optimal UV curing time and sodium benzoate content were about 10 min and 0.1 wt%, respectively. The biomaterials were characterized by SEM and FT-IR analysis. Mechanical properties of prepared AR imprinted biomaterials were also investigated. AR release was examined with changes of pH at 36.5 °C. The AR release ratio was also investigated using artificial skin. It was found that AR was released constantly for 40 min. Results of drug release mechanism indicated that AR release followed the Fickian diffusion behavior, whereas drug release using artificial skin followed the non-Fickian diffusion behavior. Tyrosinase inhibitory (%) for AR imprinted biomaterials with/without the addition of GL were 58.8% and 79.2%, respectively.

3D-Printed Titanium Cage with PVA-Vancomycin Coating Prevents Surgical Site Infections (SSIs).

Many coating materials have been studied to prevent surgical site infections (SSIs). However, antibacterial coating on surfaces show weak adhesion using the traditional titanium (Ti) cage, resulting in low efficacy for preventing SSIs after spinal surgery. Herein, a 3D-printed Ti cage combined with a drug-releasing system is developed for in situ drug release and bacteria killing, leading to prevention of SSIs in vitro and in vivo. First, a 3D-printed Ti cage is designed and prepared by the Electron Beam Melting (EBM) method. Second, polyvinyl alcohol (PVA) containing hydrophilic vancomycin hydrochloride (VH) is scattered across the surface of 3D-printed porous Ti (Ti-VH@PVA) cages. Ti-VH@PVA cages show an efficient drug-releasing profile and excellent bactericidal effect for three common bacteria after more than seven days in vitro. In addition, Ti-VH@PVA cages exhibit reliable inhibition of inflammation associated with Staphylococcus aureus and effective bone regeneration capacity in a rabbit model of SSIs. The results indicate that Ti-VH@PVA cages have potential advantages for preventing SSIs after spinal surgery.

Poly(vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism.

In the current clinical boron neutron capture therapy (BNCT), p-boronophenylalanine (BPA) has been the most powerful drug owing to its ability to accumulate selectively within cancers through cancer-related amino acid transporters including LAT1. However, the therapeutic success of BPA has been sometimes compromised by its unfavorable efflux from cytosol due to their antiport mechanism. Here, we report that poly(vinyl alcohol) (PVA) can form complexes with BPA through reversible boronate esters in aqueous solution, and the complex termed PVA-BPA can be internalized into cancer cells through LAT1-mediated endocytosis, thereby enhancing cellular uptake and slowing the untoward efflux. In in vivo study, compared with clinically used fructose-BPA complexes, PVA-BPA exhibited efficient tumor accumulation and prolonged tumor retention with quick clearance from bloodstream and normal organs. Ultimately, PVA-BPA showed critically enhanced antitumor activity in BNCT. The facile technique proposed in this study offers an approach for drug delivery focusing on drug metabolism.

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages.

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.

Controlled Release of Lidocaine-Diclofenac Ionic Liquid Drug from Freeze-Thawed Gelatin/Poly(Vinyl Alcohol) Transdermal Patches.

The objectives of this work were to prepare a 5 wt% lidocaine-diclofenac ionic liquid drug-loaded gelatin/poly(vinyl alcohol) transdermal patch using a freeze/thaw method and to evaluate its physicochemical properties, in vitro release of lidocaine and diclofenac, and stability test. The lidocaine-diclofenac ionic liquid drug was produced by the ion pair reaction between the hydrochloride salts of lidocaine and the sodium salts of diclofenac. The thermal properties of the final drug product were significantly changed from the primary drugs. The ionic liquid drug could be dissolved in water and mixed in a polymer solution. The resulting transdermal patch was then exposed to 10 cycles of freezing and thawing preparation at - 20°C for 8 h and at 25°C for 4 h, respectively. As a result, it was found that the lidocaine-diclofenac ionic liquid drug-loaded transdermal patch showed good physicochemical properties and could feasibly be used in pharmaceutical applications. The lidocaine-diclofenac ionic liquid drug was not affected by the properties of the transdermal patch due to the lack of chemical interaction between polymer base and drug. The high drug release values of both lidocaine and diclofenac were controlled by the gelatin/poly(vinyl alcohol) transdermal patch. The patch showed good stability over the study period of 3 months when kept at 4°C or under ambient temperature.

Improvement of nutrients removal from domestic wastewater by activated-sludge encapsulation with polyvinyl alcohol (PVA).

Conventional activated-sludge (AS) technologies are deficient for nutrient removal because they require specific floc characteristics. Therefore, the encapsulated AS with polyvinyl alcohol (PVA) will favor floc's formation that removes nutrients. The applied method was based on monitoring the removal of organic matter and nutrients (NH4+, NO3-, NO2-, PO43-) from synthetic domestic wastewater using laboratory-scale AS. The experimental reactors were operated at 8 h as optimized Hydraulic Retention Time (HRT). The sludge characteristics evaluation was carried out through the Sludge Volumetric Index (SVI), Food/Microorganism ratio (F/M), and Mixed Liquor Volatile Suspended Solids (MLVSS). Other specific floc characteristics, such as zeta potential and effective diameter were also evaluated. The results showed that the encapsulated AS with PVA favors nitrogen and phosphorous removal up to 35% but it did not improve organic matter removal. In addition, encapsulated AS with PVA has the characteristics of filamentous sludge (F/M: 0.7 g COD g-1 MLVSS d-1) with good settleability conditions (SVI: 43 mL g-1 MLSVS h-1) and low zeta potential (ZP: -0.9 mV), which favors its separation from the liquid phase. In conclusion, the encapsulation of AS with PVA improves nutrient removal by improving floc characteristics.

Uptake and Release of Polyvinyl Alcohol from Hydrogel Daily Disposable Contact Lenses.

SIGNIFICANCE: Polyvinyl alcohol is a wetting agent that could reduce the symptoms of dry eye and contact lens discomfort. Currently, only one lens type, nelfilcon A (DAILIES AquaComfort Plus), releases polyvinyl alcohol. The concept of releasing this agent from contact lenses could be applied to other lens materials. PURPOSE: The purpose of this study was to measure the release of polyvinyl alcohol from commercially available hydrogel daily disposable contact lenses using refractive index and iodine-borate methods. METHODS: Etafilcon A, omafilcon A, and nelfilcon A were soaked in phosphate-buffered saline and 0.2% trifluoroacetic acid/acetonitile for 24 hours to remove residual blister pack components. The lenses were then incubated in a 10-mg/mL solution of polyvinyl alcohol for 24 hours. After the incubation period, the lenses were placed in 2 mL of phosphate-buffered saline. At specified time intervals, t = 0.5, 1, 2, 4, 8, 12, and 24 hours, the samples were evaluated using refractive index and an iodine-borate assay. Polyvinyl alcohol uptake was determined by extracting the lenses with methanol for 24 hours. RESULTS: There were no differences in the uptake of polyvinyl alcohol between lens types (P > .05). The release of this wetting agent for all lens types followed a burst-plateau profile after the first 30 minutes (P > .05). Nelfilcon A had a slightly higher release of polyvinyl alcohol (P < .05) than did etafilcon A but was similar to omafilcon A (P > .05). CONCLUSIONS: The results suggest that the contact lenses tested in this study have similar efficiency in delivering polyvinyl alcohol.

In vitro and in vivo evaluation of pirfenidone loaded acrylamide grafted pullulan-poly(vinyl alcohol) interpenetrating polymer networks.

The aim of present study was to develop controlled release formulation of pirfenidone using acrylamide grafted pullulan. Interpenetrating polymer network (IPN) microspheres were prepared using acrylamide grafted pullulan and PVA utilizing glutaraldehyde assisted water-in-oil emulsion crosslinking method. IPN microspheres were characterized by FTIR, solid state 13C NMR and XRD spectroscopy. In vitro enzymatic degradation study showed 34.30% degradation after 24 h with degradation rate constant of 0.0088 min-1. In vitro biocompatibility test showed no changes in cellular morphology and cell adherence to microspheres, indicating its biocompatible nature. The release exponent value of all formulations was less than 0.45, indicating the release mechanism to be Fickian diffusion. Finally, in vivo pharmacokinetic study showed longer Tmax (1.16 h) and greater AUC value (10037.76 ng h/mL,) as compared to Pirfenex® (Tmax = 0.5 h; AUC = 4310.45 ng h/mL,). The results indicated that the prepared formulation could successfully control the drug release for prolonged time period.

Molecular encapsulator-appended poly(vinyl alcohol) shroud on ferrite nanoparticles. Augmented cancer-drug loading and anticancer property.

Magnetic nanoparticles (MNPs) have the potency to deliver cancer drugs assisted by the application of a magnetic field. In this paper, we present the design of magnesium ferrite nanoparticles of size suitable for drug delivery. A coating polymer, poly(vinyl alcohol), tethered with a tapered cone-shaped cyclic oligosachcharide, ß-cyclodextrin (ß-CD) is synthesized and used to wrap and disperse the MNPs. The magnetic properties are explored using vibrating sample magnetometry and Mössbauer spectroscopy. The ∑130 nm MNPs, shrouded with the PVA-CD conjugate allows a high amount of the cancer drug, camptothecin, to be loaded on the nanocarrier. Cytotoxicity studies reveal that the loaded drug retains its potency against HEK 293 cells and the cells are sensitive to the treatment by the drug-loaded nanocarrier.

Fabrication of electrospun poly(vinyl alcohol)/dextran nanofibers via emulsion process as drug delivery system: Kinetics and in vitro release study.

A green electrospinning was used for the fabrication of PVA/Dex (dextran sulfate) nanofibers as a carrier for drug delivery. Core-shell nanofibers were fabricated by emulsion electrospinning from PVA/Dex loaded with ciprofloxacin (Cipro) as a model drug. The ratio of the PVA/Dex mixture was optimized and nanofibers were stabilized against disintegration in water by thermal treatment at 120 °C. The morphology of the prepared nanofibers was observed by scanning electron microscopy (SEM) and the core-shell structure of the nanofibers was confirmed by transmission electron microscopy (TEM). Drug entrapment was confirmed by Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The interaction between PVA and Dex was affirmed by differential scanning calorimetry (DSC). In vitro drug release was monitored by UV-vis spectrophotometer and its associated mechanism was studied using diverse kinetic models. The release study demonstrated that the core-shell nanofibers can sustain the Cipro release compared with the blending electrospinning nanofibers. Moreover, the drug release mechanism is controlled by the Dex content of the polymer blends and can occur by diffusion within the delivery system. It is anticipated that Cipro@PVA/Dex nanofibers are promising eco-friendly drug delivery system which can be prepared by a green method.

Influence of Polysorbate 60 on Formulation Properties and Bioavailability of Morin-Loaded Nanoemulsions with and without Low-Saponification-Degree Polyvinyl Alcohol.

The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets. MCT-LL810 nanoemulsion containing LL-810 was prepared with a reduced amount of Tween 60. However, the area under the blood concentration-time curve (AUC) of MCT-LL810 (0.18) nanoemulsion containing a small amount of Tween 60 did not increase because the absorption of morin was limited by P-glycoprotein (P-gp)-mediated efflux. MCT-LL810 (0.24) nanoemulsion containing a large amount of Tween 60 showed the highest AUC, dispersed droplets containing Tween 60 may have been transported into epithelial cells in the small intestine, and P-gp transport activity appeared to be suppressed by permeated Tween 60. Based on the plasma concentration profile, dispersed droplets in MCT-LL810 (0.24) nanoemulsion permeated more rapidly through the mucus layer and the intestinal membrane than MCT (0.24) nanoemulsion without LL-810. In conclusion, a novel feature of Tween 60 incorporated into the dispersed droplets of a nanoemulsion interacting with P-gp was demonstrated herein. Dispersed droplets in MCT-LL810 (0.24) nanoemulsion containing LL-810 permeated rapidly through the mucus layer and intestinal membrane, and Tween 60 incorporated in dispersed droplets interacted with P-gp-mediated efflux, increasing the bioavailability of morin.

Polymer conjugated retinoids for controlled transdermal delivery.

All-trans retinoic acid (ATRA), a derivative of vitamin A, is a common component in cosmetics and commercial acne creams as well as being a first-line chemotherapeutic agent. Today, formulations for the topical application of ATRA rely on creams and emulsions to incorporate the highly hydrophobic ATRA drug. These strategies, when applied to the skin, deliver ATRA as a single bolus, which is immediately taken up into the skin and contributes to many of the known adverse side effects of ATRA treatment, including skin irritation and hair loss. Herein we present a new concept in topical delivery of retinoids by covalently bonding the drug through a hydrolytically degradable ester linkage to a common hydrophilic polymer, polyvinyl alcohol (PVA), creating an amphiphilic nanomaterial that is water-soluble. This PVA bound ATRA can then act as a pro-drug and accumulate within the skin to allow for the sustained controlled delivery of active ATRA. This approach was demonstrated to release active ATRA out to 10days in vitro while significantly enhancing dermal accumulation of the ATRA in explant pig skin. In vivo we demonstrate that the pro-drug formulation reduces application site inflammation compared to free ATRA and retains the drug at the application site at measurable quantities for up to six days.

Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets using PEG and hard fat showed sufficient adhesiveness and sustained drug release, those using PEG as the base did not. Drug release was controlled by the amount of hard fat and the saponification degree of PVA. The drug release rate was most increased in a tablet containing PVA with an intermediate degree of saponification, PEG and hard fat. From differential scanning calorimetry and powder X-ray diffraction, IM was considered to exist in the molecular phase. From the results of buccal administration of tablets to rats, highest tissue concentrations were observed in the tablet containing PVA with the intermediate degree of saponification using PEG and hard fat, and the plasma concentrations were sufficiently low in comparison.

Ofloxacin loaded gellan/PVA nanofibers - Synthesis, characterization and evaluation of their gastroretentive/mucoadhesive drug delivery potential.

The purpose of this investigation is to formulate a gastroretentive sustained drug release system for ofloxacin to improve its retention time, pharmacological activity, bioavailability and therapeutic efficacy in the stomach. Ofloxacin loaded gellan/poly vinyl alcohol (PVA) nanofibers were fabricated using a simple and versatile electrospinning technique. The fabricated nanofibers were evaluated for percent drug encapsulation efficiency and in vitro drug release in simulated gastric medium (pH1.2). The in vitro release profile and kinetic studies for drug indicated the sustained release of ofloxacin from the nanofibers through Fickian diffusion kinetics. The antimicrobial activity of the ofloxacin loaded nanofibers was assessed in comparison to the pure ofloxacin by means of minimal inhibitory concentrations (MIC) against microbial strains of Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The optimized ofloxacin loaded gellan/PVA nanofibers displayed biphasic drug release profile with considerable mucoadhesion and gastric retention in the rat's gastric mucosal membrane. Data obtained, suggested that the developed gastroretentive drug delivery can potentially enhance the pharmacological activity of ofloxacin and can also serve as a viable alternative for improving drug bioavailability via oral route.

Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients.

Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating nanocrystals of poorly water-soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. Organic phase nanoemulsion droplets stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors. Controlled evaporation of this composite material produces core-shell structured alginate-PVA hydrogels with drug nanocrystals (500-650 nm) embedded within the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved with dissolution (of 80% of the drug) occurring in as little as 30 min. A quantitative model is also developed and experimentally validated that the drug release patterns of the fenofibrate nanocrystals can be modulated by controlling the thickness of the PVA shell and drug loading. Thus, these composite materials offer a "designer" drug delivery system. Overall, our approach enables a novel means of simultaneous controlled crystallization and formulation of hydrophobic drugs that circumvents energy intensive top-down processes in traditional manufacturing.

A double-layer patch design for local and controlled drug delivery as an intraoperative custom-made implant-coating technology.

BACKGROUND: The specific biological need of patients frequently becomes obvious just in the intraoperative setting. We hypothesized that a double-layer patch approach that allowed rapid attachment to an implant surface would represent a potential solution for technically challenging intraoperative personalized local drug delivery. METHODS: Dexamethasone-loaded poly[(rac-lactide)-co-glycolide] (PLGA) microparticles were embedded within a polyvinyl alcohol (PVA) patch that was attached to metal implant surfaces by in situ polymerization of alkyl-2-cyanoacrylates (CAs). Hydroxyapatite (HA) nanoparticles were also embedded in the PVA patch. RESULTS: Very rapid dexamethasone-release profiles were observed from the PLGA microparticles / PVA patches. The incorporation of HA nanoparticles into the PVA enabled control of CA penetration within the patch, and improved significantly its attachment, while no interference with the drug release was observed. CONCLUSIONS: Double-layered patches with 1 layer for drug delivery and 1 as gluing interface could represent a solution for safe and controlled local drug delivery from implant surfaces or other, even biological, materials. The technology platform presented here opens the opportunity for personalized medicine by allowing local administration of drugs with customized release based on an intraoperative application.