Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica.

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. STATEMENT OF SIGNIFICANCE: Lumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.

Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy.

High-throughput quantification of the first- and second-phase insulin secretion dynamics is intractable with current methods. The fact that independent secretion phases play distinct roles in metabolism necessitates partitioning them separately and performing high-throughput compound screening to target them individually. We developed an insulin-nanoluc luciferase reporter system to dissect the molecular and cellular pathways involved in the separate phases of insulin secretion. We validated this method through genetic studies, including knockdown and overexpression, as well as small-molecule screening and their effects on insulin secretion. Furthermore, we demonstrated that the results of this method are well correlated with those of single-vesicle exocytosis experiments conducted on live cells, providing a quantitative reference for the approach. Thus, we have developed a robust methodology for screening small molecules and cellular pathways that target specific phases of insulin secretion, resulting in a better understanding of insulin secretion, which in turn will result in a more effective insulin therapy through the stimulation of endogenous glucose-stimulated insulin secretion.

Biphasic drug release from electrospun structures.

INTRODUCTION: Biphasic release, as a special drug-modified release profile that combines immediate and sustained release, allows fast therapeutic action and retains blood drug concentration for long periods. Electrospun nanofibers, particularly those with complex nanostructures produced by multi-fluid electrospinning processes, are potential novel biphasic drug delivery systems (DDSs). AREAS COVERED: This review summarizes the most recent developments in electrospinning and related structures. In this review, the role of electrospun nanostructures in biphasic drug release was comprehensively explored. These electrospun nanostructures include monolithic nanofibers obtained through single-fluid blending electrospinning, core-shell and Janus nanostructures prepared via bifluid electrospinning, three-compartment nanostructures obtained via trifluid electrospinning, nanofibrous assemblies obtained through the layer-by-layer deposition of nanofibers, and the combined structure of electrospun nanofiber mats with casting films. The strategies and mechanisms through which complex structures facilitate biphasic release were analyzed. EXPERT OPINION: Electrospun structures can provide many strategies for the development of biphasic drug release DDSs. However, many issues such as the scale-up productions of complex nanostructures, the in vivo verification of the biphasic release effects, keeping pace with the developments of multi-fluid electrospinning, drawing support from the state-of-the-art pharmaceutical excipients, and the combination with traditional pharmaceutical methods need to be addressed for real applications.

Integration of lornoxicam nanocrystals into hydroxypropyl methylcellulose-based sustained release matrix to form a novel biphasic release system.

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC). Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet. Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared to the reference product.

Simultaneous solubilization and extended release of insoluble drug as payload in highly soluble particles of γ-cyclodextrin metal-organic frameworks.

The inclusion and nanocluster formed in cyclodextrin-metal organic framework (CD-MOF) make it a remarkable vehicle in improving the solubility and bioavailability of insoluble drugs, but rarely in elongation of drug release kinetics. In this research, an insoluble compound, 18ß-glycyrrhetinic acid (GA), encapsulated in CD-MOF (GA@nano-CD-MOF) had prominent effects in the treatment of bleomycin-induced idiopathic pulmonary fibrosis in rats with an enhanced bioavailability by 6.8 times. The solubility of GA@nano-CD-MOF was 7780 times higher than that of GA, which was explained by the solubility parameter of amorphous cells constructed in silico simulation. CD-MOF imparted GA unique biphasic release kinetics, namely, GA released instantly to 52% and slowly released to 100% for a period of 5 days, which made the drug loaded particles much more flexible in pharmaceutical applications. The distribution of GA molecules in CD-MOF and drug loading priority obtained by molecular docking illustrated the formation of biphasic release mode at the molecular level combined with other characterizations of SEM, PXRD, TGA and DSC. In conclusion, CD-MOF has a unique effect to simultaneously solubilize an insoluble drug and extend its release for days as payload in highly soluble particles of γ-cyclodextrin metal-organic frameworks, which broaden the applications of drugs in specific treatment and then enhance the therapeutic effects.

Trilayer microneedle array assisted transdermal and intradermal delivery of dexamethasone.

Dexamethasone is a synthesised glucocorticoid that is widely used in the treatment of various inflammatory skin conditions. Novel trilayer dissolving microneedle arrays were manufactured to assist dexamethasone delivery via the skin. Both transdermal delivery and intradermal delivery of dexamethasone can be achieved this way. Additionally, we proposed a novel strategy of co-formulating dexamethasone and its pro-drug dexamethasone sodium phosphate into the same dissolving microneedle array, with a view to achieving a fast onset of action and also sustained treatment. Here, a 3D-printing technique was employed, for the first time, to fabricate a baseplate for these microneedle arrays. The 3D-printed baseplates provided strong support to aid the insertion of the drug-encapsulated tips. A simple and rapid HPLC method was developed, and validated, to separate and quantify dexamethasone and dexamethasone sodium phosphate in the same sample. Ex-vivo studies found that these trilayer dissolving microneedle arrays could achieve a delivery efficiency of over 40% in intradermal delivery and over 50% in transdermal delivery. Trilayer microneedle-assisted delivery of this glucocorticoid provided a promising alternative to oral and parenteral routes of dexamethasone administration.

Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique.

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion-melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.

Preparation and Physicochemical Characterization of Water-Soluble Pyrazole-Based Nanoparticles by Dendrimer Encapsulation of an Insoluble Bioactive Pyrazole Derivative.

2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4) was synthetized and successfully evaluated concerning numerous biological activities, except for antimicrobial and cytotoxic effects. Due to the antimicrobial effects possessed by pyrazole nucleus, which have been widely reported, and the worldwide need for new antimicrobial agents, we thought it would be interesting to test BBB4 and to evaluate its possible antibacterial effects. Nevertheless, since it is water-insoluble, the future clinical application of BBB4 will remain utopic unless water-soluble BBB4 formulations are developed. To this end, before implementing biological evaluations, BBB4 was herein re-synthetized and characterized, and a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants. The obtained BBB4 nanoparticles (BBB4-G4K NPs) showed good drug loading (DL%), satisfying encapsulation efficiency (EE%), and a biphasic quantitative release profile governed by first-order kinetics after 24 h. Additionally, BBB4-G4K was characterized by ATR-FTIR spectroscopy, NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While, before the nanotechnological manipulation, BBB4 was completely water-insoluble, in the form of BBB4-G4K NPs, its water-solubility resulted in being 105-fold higher than that of the pristine form, thus establishing the feasibility of its clinical application.

Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy.

Hypertrophic scar (HS) is an undesirable skin abnormality following deep burns or operations. Although intralesional multi-injection with the suspension of triamcinolone acetonide (TA) and 5-fluorouracil (5-Fu) has exhibited great promise to HS treatment in clinical, the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy. Besides, the traditional injection with great pain is highly dependent on the skill of the experts, which results in poor compliance. Herein, a bilayer dissolving microneedle (BMN) containing TA and 5-Fu (TA-5-Fu-BMN) with biphasic release profile was designed for HS therapy. Equipped with several micro-scale needle tips, the BMN could be self-pressed into the HS with uniform drug distribution and less pain. Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property. Subsequently, the rabbit ear HS model was established to assess therapeutic efficacy. The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition. It was also found that the value of scar elevation index was ameliorated to a basal level, together with the downregulation of mRNA and protein expression of Collagen I (Col I) and transforming growth factor-ß1 (TGF-ß1) after application of TA-5-Fu-BMN. In conclusion, the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.

Combination of structure-performance and shape-performance relationships for better biphasic release in electrospun Janus fibers.

In nature, the combination of composition, structure, and shape determines the matter's functional performance to a large extent. Inspired by which, two electrospun Janus nanofiber formulations were created using side-by-side electrospinning in this work. Tamoxifen citrate (TAM) was used as a model drug and ethyl cellulose (EC) and polyvinylpyrrolidone K60 (PVP) as the polymer carrier matrices. The fibers have linear cylindrical morphologies and distinct Janus structures by scanning electron microscopy. One side of the fibers took a round shape, while the other was crescent-shaped. The drug was present in both polymer matrices in the form of amorphous solid dispersions, owing to strong intermolecular interactions between drug and polymer. In vitro dissolution tests demonstrated that both sets of fibers could provide biphasic drug release due to the difference in solubility of PVP and EC. The different shape of TAM-EC and TAM-PVP side of the Janus structure resulted in a considerable variation in the drug release profiles. The Janus structure with crescent TAM-PVP side and round TAM-EC side gave a more rapid burst release in the first phase of release, and slower sustained release in the second phase. This work thus reports a new strategy for systematically developing advanced functional nanomaterials based on both shape- and structure-performance relationships.

Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells.

Thymoquinone (TQ), a natural polyphenol, has been associated with various pharmacological responses; however, low bioavailability of TQ limits its clinical application. Thus, a novel phytosomal delivery system of TQ-Phospholipon® 90H complex (TQ-phytosome) was developed by refluxing combined with anti-solvent precipitation. This TQ delivery system was optimized by a three-factor, three-level Box-Behnken design. The optimized TQ-phytosome size was (45.59 ± 1.82 nm) and the vesicle size was confirmed by transmission electron microscopy. The in vitro release pattern of the formulation indicated a biphasic release pattern, where an initial burst release was observed within 2 h, followed by a prolonged release. A remarkable increase in dose-dependent cytotoxicity was evident from the significant decrease in IC50 value of TQ-phytosomes (4.31 ± 2.21 µM) against the A549 cell line. The differential effect of TQ-phytosomes in cell cycle analysis was observed, where cancer cells were accumulated on G2-M and pre-G1 phases. Furthermore, increased apoptotic induction and cell necrosis of TQ-phytosomes were revealed with the annexin V staining technique via activation of caspase-3. In reactive oxygen species (ROS) analysis, TQ-phytosomes acted to significantly increase ROS generation in A549 cells. In conclusion, the sustained release profile with significantly-improved anticancer potential could be obtained with TQ by this phytosomal nanocarrier platform.

Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery.

In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers. Histological examination confirmed that the microneedles were successfully inserted into the skin and indicated biphasic release of dyes incorporated within microneedle matrices. Structural changes of a model protein drug, bovine serum albumin (BSA), in PLGA and PVP matrices were examined by circular dichroism (CD) and fluorescence spectroscopy. The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile.

A comparative study of single-needle and coaxial electrospun amyloid-like protein nanofibers to investigate hydrophilic drug release behavior.

In this study, nanofibers containing an amyloid-like bovine serum albumin (AL-BSA) carrier and a model drug (ampicillin) were produced by electrospinning. The release behavior of ampicillin was compared from electrospun nanofibers prepared as either coaxial or single-needle types. SEM images showed that the membranes had a uniform and smooth structure and the core/shell fibers were found to be thicker than the core fibers. Core/shell production was proved by transmission electron microscopy images. Fourier transform infrared spectroscopy indicated the existence of compatibility between ampicillin and the AL-BSA matrix. The in vitro antimicrobial properties of ampicillin were studied through the comparison of bacterial inhibition zones and ampicillin was found to be more effective against Gram-positive Staphylococcus aureus than Gram-negative Escherichia coli. Moreover, in vitro drug release tests were conducted to explore the relationship between the shell thickness and the drug release rate. A burst release was observed for all membranes owing to the small fiber diameters and thus short diffusion lengths. For core membranes, the drug release mechanism followed Fickian transport, which was close to zero-order kinetic. A typical biphasic release mechanism was observed for the core/shell nanofibers. Overall, we present the first evidence of AL-BSA as a potential core/shell drug mediator.

Development and evaluation of multiparticulate biphasic system for the treatment of circadian diseases

Multiparticulate systems have biopharmaceutical advantages when compared to the monolithic systems, once they allow different patterns of drug release and can be used in different treatments. The aim of the present work was to develop a biphasic controlled release delivery system, using propranolol hydrochloride (PROP) that can be used for the treatment of circadian diseases. This system was obtained by the combination of cellulosic polymers hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) in a 2² factorial experimental design, which allowed the optimization of the development stage. The pellets produced and used in biphasic formulations were evaluated for physical and chemical characteristics and presented acceptable results. The immediate fraction obtained showed the complete release in 30 min while the others kept the release of the drug for 24 h. This study showed that the combination of beads with different releasing characteristics allowed to obtain different release profiles, which can be modulated according to the pathological needs, especially with regard to circadian diseases that suffer alterations throughout the day.

Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles.

Simple sequential electrospinning was utilized to create a functional tri-layered nanofiber mesh that achieves time-regulated biphasic drug release behavior. A tri-layered nanofiber mesh -composed of zein and poly(vinylpyrrolidone) (PVP) as the top/bottom and middle layers, respectively - was constructed through sequential electrospinning with ketoprofen (KET) as the model drug. PVP was blended with graphene oxide (GO) to improve the drug release functionality of PVP nanofiber as well as its mechanical properties. Scanning electron microscopy confirmed that the resultant nanofibers had a linear morphology, smooth surface, and tri-layered structure. In addition, X-ray diffraction patterns, differential scanning calorimetric analyses, and Fourier transform infrared spectra verified that the drugs were uniformly dispersed throughout the nanofiber due to good compatibility between the polymer and KET induced by hydrogen interaction. In vitro release test of the tri-layered structure, each component of which had distinct release features, successfully demonstrated time-regulated biphasic drug release. Also, it was confirmed that the drug release rate and duration can be controlled by designing a morphological feature - namely, mesh thickness - which was achieved by simply regulating the spinning time of the first and third layer. This multilayered electrospun nanofiber mesh fabricated by sequential electrospinning could provide a useful method of controlling drug release behavior over time, which will open new routes for practical applications and stimulate further research in the development of effective drug release carriers.

Preparation of lansoprazole biphasic release pellet capsules / 国际药学研究杂志

Objective To prepare lansoprazole biphasic release pellet capsules. Methods The pellets carrying lansoprazole were directly prepared by centrifugal making-pill method,and the pellets of enteric coating and enteric pulsatile coating were adopted by fluidized bed coating method. Then the two kinds of pellets were filled by a fixed proportion to hollow capsules. In vitro dissolution method was used for the observation of the drug release behavior. Results The optimized formulation was as follows:the magnesium carbonate level was 15%,the L-HPC level was 20%in pellets carried drug,the isolation gown level was 9%-10%,the enteric coating level was above 41%in enteric coated pellets,the swelling agent level was 50-60%,the controlled layer level was 50%,the enteric coating level was above 41%in pulsatile enteric coated pellets,and the drying time was 4 h in the end. Conclusion The method is feasible for preparation of lansoprazole biphasic release pellet capsules by encapsulating enteric-coated pellets,and able to obtain good repeatability and stable quality.

Preparation of lansoprazole biphasic release pellet capsules / 国际药学研究杂志

Objective To prepare lansoprazole biphasic release pellet capsules. Methods The pellets carrying lansoprazole were directly prepared by centrifugal making-pill method, and the pellets of enteric coating and enteric pulsatile coating were adopted by fluidized bed coating method. Then the two kinds of pellets were filled by a fixed proportion to hollow capsules. In vitro dissolution method was used for the observation of the drug release behavior. Results The optimized formulation was as follows: the magnesium carbonate level was 15%, the L-HPC level was 20% in pellets carried drug, the isolation gown level was 9%-10%, the enteric coating level was above 41% in enteric coated pellets, the swelling agent level was 50-60%, the controlled layer level was 50%, the enteric coating level was above 41% in pulsatile enteric coated pellets, and the drying time was 4 h in the end. Conclusion The method is feasible for preparation of lansoprazole biphasic release pellet capsules by encapsulating enteric-coated pellets, and able to obtain good repeatability and stable quality.

A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.

The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.

Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process.

This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned.

Biphasic release of protein from polyethylene glycol and polyethylene glycol/modified dextran microspheres.

Dextrans show great promise for delivery of therapeutic agents. Dextran acetates (DAs) were synthesized with increasing degrees of substitution (DA1 < DA2 < DA3) by the reaction of the polysaccharide dextran (70 kDa) with acetic anhydride. A series of polyethylene glycol (PEG)/DA microspheres were prepared and tested with bovine serum albumin (BSA) functioning as a model protein. Particle size (0.74-0.85 µm) and encapsulation efficiency (56-70%) increased with the degree of substitution along with a slower release rate of protein from PEG/DA microspheres. Time to release 90% of protein rose from 31 to 118 min. Percentage of BSA released from PEG and PEG/DA3 microspheres with time (min) was modeled mathematically [Y(PEG) = 100(1 - e(-0.12t)); Y(PEG/DA3) = 100(1 - e(-0.024t))] to predict cumulative delivery from mixtures in vitro over a period of hours when constrained to a target level at 30 min. The system is examined for potential application in thrombolytic therapy.