Tethered drug release from model contact lenses

Drug delivery to the eye remains a challenge due to low compliance and high amounts of drug loss resulting from anatomical barriers. Contact lens-based delivery systems offer many advantages since their increased corneal residence time can increase drug bioavailability. A releasable, sustained delivery system from a contact lens has been evaluated in the current work. Using a labile lactide spacer, comprised of poly(ethylene glycol) methacrylate, varying numbers of lactide units and succinic anhydride, a model drug, R-roscovitine, was covalently incorporated into model silicone lenses (consisting of 80 mol% N,N-dimethylacrylamide and 20 mol% of a modified silicone). This enabled a greater amount of the drug to remain in the material following extraction with isopropyl alcohol, a common purification procedure used in lens manufacturing. The incorporation of the tether and drug did not substantially alter the bulk properties of the materials, with their water content remaining between 32% and 36% and their transmittance remaining at over 90% at 600 nm. Drug release from these materials exceeded 2 weeks, with the longer lactide tethers showing greater release as expected. This demonstrates that these covalently modified materials have the potential to be used to deliver drugs in a sustained manner. © 2022 Society of Industrial Chemistry.     

Sequential release of multiple drugs from flexible drug delivery films

Sequential release of drugs aligned with the phases of tissue healing could reduce scarring. To achieve this aim, layered film devices comprising cellulose acetate phthalate (CAP) and Pluronic F-127 (Pluronic) were loaded with ketoprofen, quercetin, and pirfenidone. Citrate plasticizers were added to impart flexibility. Release of two or three drugs in sequence over several days was obtained for all multilayered devices tested. Mechanical analysis showed that elongation increased and modulus decreased with the increasing plasticizer content. Release profiles can be tailored by order of layers, plasticizer concentration, and drug loading, making CAP–Pluronic an appealing system for inhibiting scar tissue formation.     

Responsive polymeric nanoparticles for controlled drug delivery

Small‐molecule drugs often have limited solubility, display rapid clearance or poor selectivity that leads to undesired side‐effects. Although prodrug strategies can improve solubility and lower toxicity, activation ‘on demand’ as well as targeted transport of prodrugs remains a challenge in drug delivery. Responsive polymeric nanoparticles can help meet these challenges with the encapsulation or conjugation of drugs, allowing release at the target site upon triggering by an internal or external stimulus. The adaptable design of polymeric nanoparticles allows them to play a vital role in achieving a specific and desired response following application of a specific stimulus. Here, the most recent progress in responsive polymeric nanoparticles is reviewed with a focus on the chemical properties of the utilized polymers. © 2017 Society of Chemical Industry     

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix^® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise^®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix^® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.     

聚天冬氨酸衍生物药物控释体系的研究进展

聚天冬氨酸衍生物是一种可生物降解并具有生物相容性的新材料。综述了聚天冬氨酸衍生物药物控制释放体系的研究进展,重点探讨了聚天冬氨酸衍生物共价复合大分子药物、微凝胶、微胶束等药物缓释体的制备方法及性能,展望了聚天冬氨酸衍生物在药物控释、组织工程等领域的应用前景。     

Engineering a drug eluting ocular patch for delivery and sustained release of anti-inflammatory therapeutics

Ocular inflammation is commonly associated with eye disease or injury. Effective and sustained ocular delivery of therapeutics remains a challenge due to the eye physiology and structural barriers. Herein, we engineered a photocrosslinkable adhesive patch (GelPatch) incorporated with micelles (MCs) loaded with loteprednol etabonate (LE) for delivery and sustained release of drug. The engineered drug loaded adhesive hydrogel, with controlled physical properties, provided a matrix with high adhesion to the ocular surfaces. The incorporation of MCs within the GelPatch enabled solubilization of LE and its sustained release within 15 days. In vitro studies showed that MC loaded GelPatch supported cell viability and growth. In addition, subcutaneous implantation of the MC loaded GelPatch in rats confirmed its in vivo biocompatibility and stability within 28 days. This non-invasive, adhesive, and biocompatible drug eluting patch can be used as a matrix for the delivery and sustained release of hydrophobic drugs.     

玉米醇溶蛋白用作药物输送系统载体的研究进展

玉米醇溶蛋白(Zein)是一种天然可食性植物大分子,具有可再生性、无毒性、两亲性及良好的生物相容性和生物可降解性,可通过自组装形成微球或纳米粒。近年来,Zein用作药物输送系统(drug delivery system,DDS)载体材料成为研究热点,可通过Zein的自组装特性将药物包载在其内部获得Zein-DDS微粒。本文简述了Zein的特性及其作为DDS载体的优势,总结了Zein-DDS的制备方法、性能及Zein的修饰改性研究进展,指出Zein具有较强的疏水性和抗胃酸分解特性,Zein-DDS可有效地提高药物稳定性、延缓药物释放及增强药物靶向性。因此,Zein用作DDS的载体具有广阔的应用前景,今后的研究工作将会在拓宽研究领域、改进制备方法及Zein的修饰改性等方面展开。     

Effect of fluorinated hydrophobic monomer on the drug release behavior for the thermosensitive hydrogels

Three series of copolymeric gels based on N‐isopropylacrylamide (NIPAAm) and perfluoroalkyl methacrylate such as 2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate (OFPMA), 4,4,5,5,6,7,7,7‐octafluoro‐2‐hydroxy‐6‐(trifluoromethyl)heptyl methacrylate (OFHHMA), and 3,3,4,4,5,6,6,6‐octafluoro‐5‐(trifluoromethyl)hexyl methacrylate (OFHMA), were prepared by emulsion polymerization. The effect of perfluoroalkyl methacrylate and sodium lauryl sulfate (SLS), which can act as a surfactant and a pore‐forming agent, on the equilibrium swelling ratio and mechanical properties of the present hydrogels was investigated. Results show that hydrophobic monomers made the swelling ratio of the gel decrease and the mechanical property of the gel increase; however, SLS exhibits a contrary result. In addition, the effect of perfluoroalkyl methacrylate on the drug release behavior was also investigated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4661–4667, 2006     

Recent advances in drug delivery systems based on polypeptides prepared from N‐carboxyanhydrides

Recent years have seen a dramatic increase in interest in the use of ring‐opening polymerization of N‐carboxyanhydride monomers as a method to prepare well‐defined polypeptides and peptide hybrid materials. The resulting molecules are often capable of assembling into a variety of different structures, including micelles, vesicles, nanoparticles and hydrogels, and therefore have been explored as novel drug delivery systems. Peptides are attractive in this regard due to their rich chemical functionality and ability to assemble through the formation of secondary structures (e.g. α‐helices and β‐sheets). In addition, they are inherently biodegradable and biocompatible. This review describes recent advances in the field, covering aspects such as improved methods with which to prepare better‐defined polypeptides, crosslinking of assemblies to enhance biostability, the preparation of materials that respond to a variety of stimuli (including light and intra‐ or extracellular redox conditions), functionalization with targeting ligands to enhance cellular uptake, assemblies for small interfering RNA delivery and approaches to theranostic systems. © 2014 Society of Chemical Industry     

Kinetics of drug release from drug carrier of polymer/TiO2 nanotubes composite—pH dependent study

This study was to investigate the kinetics of drug release from polymer/TiO₂ nanotubes composite. Lidocaine and carprofen were selected as model drugs to represent weak base and weak acid drugs, respectively. Mathematical models used to fit the in vitro drug release experimental data indicate that at higher pH, the drug release was first order diffusion controlled. At lower pH, the release of the two drugs exhibits two staged controlled release mechanism. The first phase is due to drug diffusion and the second stage is a result of poly(lactic‐co‐glycolic acid) (PLGA) polymer degradation. The rate of drug release from polymer/TiO₂ nanotubes drug carrier was mainly controlled by three pH dependent factors: the solubility of the drug, the degree of polymer swelling/degradation, and the electrostatic force between polymer and drug. This study suggests that controlled release could be achieved for polymer/TiO₂ nanotubes drug carrier via the modulation of pK_a values of polymers and drug solubility. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41570.     

Simulation and experimental analysis of an intelligent tissue for controlled drug delivery

In this research, an antibiotic was loaded in the composites of polyethylene glycol (PEG), acrylamide (AAm) and acrylic acid (AAc) hydrogels matrices and their drug deliveries were tested. Effect of some parameters on the drug delivery was checked by UV‐spectrophotometer. Temperature enhancement considerably increased hydrogel swelling and the drug release in the AAc and AAm. A dynamic model based on the Maxwell–Stefan equation was developed to model the drug delivery of hydrogels. COMSOL software was also applied to simulate buffer diffusion inside the hydrogels.     

Stimuli-accelerated polymeric drug delivery systems

The controlled delivery of active pharmaceutical ingredients to the site of disease represents a major challenge in drug therapy. Particularly when drugs have to be transported across biological barriers, suitable drug delivery systems are of importance. In recent years responsive delivery systems have been developed which enable a controlled drug release depending on internal or external stimuli such as changes in pH, redox environment or light and temperature. In some studies delivery systems with reactivity against two different stimuli were established either to enhance the response by synergies of the stimuli or to broaden the window of possible trigger events. In the present review numerous exciting developments of pH-, light- and redox-cleavable polymers suitable for the preparation of smart delivery systems are described. The review discusses the different stimuli that can be used for a controlled drug release of polymer-based delivery systems. It puts a focus on the different polymers described for the preparation of stimuli-sensitive systems, their preparation techniques as well as their stimuli-responsive degradation. © 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.     

pH‐sensitive swelling and release behaviors of anionic hydrogels for intelligent drug delivery system

The pH‐sensitive swelling and release behaviors of the anionic P(MAA‐co‐EGMA) hydrogels were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. There was a drastic change of the equilibrium weight swelling ratio of P(MAA‐co‐EGMA) hydrogels at a pH of around 5, which is the pK_a of poly (methacrylic acid) (PMAA). At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. When the molecular weight of the pendent poly(ethylene glycol) (PEG) of the P(MAA‐co‐EGMA) increased, the swelling ratio decreased at a pH higher than 5. The pK_a values of the P(MAA‐co‐EGMA) hydrogels moved to a higher pH range as the pendent PEG molecular weight increased. When the feed concentration of the crosslinker of the hydrogel increased the swelling ratio of the P(MAA‐co‐EGMA) hydrogels decreased at a pH higher than 5. In release experiments using Rhodamine B (Rh‐B) as a model solute, the P(MAA‐co‐EGMA) hydrogels showed a pH‐sensitive release behavior. At low pH (pH 4.0) a small amount of Rh‐B was released while at high pH (pH 6.0) a relatively large amount of Rh‐B was released from the hydrogels. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation and release kinetics of carboxymethyl chitosan/cellulose acetate microspheres as drug delivery system

Carboxymethyl chitosan, a water soluble chitosan derivative, was prepared from chitosan using monochloroacetic acid. Carboxymethyl chitosan/cellulose acetate microspheres (CCM) were prepared using the method of W/O/W and emulsification solvent evaporation as drug delivery system. The CCMs prepared were spherical, free‐flowing, and nonaggregated with the smooth appearance and many small pores on the surface. All CCMs prepared had sustained release efficiency for acetaminophen and the optimal formulation was that carboxymethyl chitosan of 2.0% and 1360 KD. In addition, the release rate of drug from CCMs in dilute hydrochloric acid was much slower than that in phosphate buffer saline (pH 6.8) during 24 h. It is illustrated that the drug loaded in CCMs released slower in simulated gastric fluid than that in simulated intestinal fluid. Furthermore, the drug release data showed better fitness with the first order model which indicated that the drug release from CCMs was depended on the drug concentration in the polymeric networks. And the release of drug from CCMs indicated diffusion‐controlled drug release based on Fickian diffusion and accompanied with anomalous transport (i.e., non‐Fickian diffusion) according to the values obtained from Higuchi model and Peppas models. So it was shown that the CCMs might be an ideal sustained release system for acid‐labile drugs both for the solubility of carboxymethyl chitosan and the release media. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42152.     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

One dose or two? The use of polymers in drug delivery

Controlled‐release delivery systems are designed to prolong the release of drugs within the body. They consist of drug molecules encapsulated within biodegradable polymers which degrade safely into small, non‐toxic fragments, resulting in the release of the drug. Because different polymers have different degradation times, the system can be tailored to achieve the desired release rate and this can be very useful in treatments where daily dosing is required, such as epilepsy. Despite this obvious advantage, there are problems with this type of delivery, including an increased risk of overdosing. This article examines the pros and cons of controlled‐release drug‐delivery systems. Copyright © 2007 Society of Chemical Industry     

Amorphous silica nanoparticles derived from biowaste via microwave combustion for drug delivery

Amorphous silica nanoparticles are a promising platform for constructing drug delivery vehicles owing to their high biocompatibility and favorable surface chemistry. In the current study, we report the preparation of amorphous silica nanoparticles using rice husk biowaste via easy and rapid microwave-assisted combustion. The obtained results from various characterizations indicate that the prepared sample is an amorphous form of silica nanoparticles having sizes 50–80 nm with high purity. Ciprofloxacin was used as the model drug and it was released from silica nanocarrier in a controlled and prolonged manner. The ciprofloxacin release kinetics was investigated using the Higuchi model and Ritger-Peppas model which corroborate that different process like desorption, diffusion, and surface erosion may be involved in the release of ciprofloxacin from the prepared silica nanocarrier. The antibacterial susceptibility test revealed that the ciprofloxacin loaded silica nanocarrier exhibit a bacterial inhibition zone about 32 ± 4 and 44 ± 3 mm against Escherichia coli and Staphylococcus aureus, respectively. This study can be useful to develop a versatile nanocarrier with controlled delivery of ciprofloxacin to treat different types of bacterial infections.     

Determination of mechanical properties of polymeric microspheres used in controlled drug delivery systems by nanoindentation

In this study, we synthesized poly (vinyl acetate-co-divinyl benzene) microspheres with various monomer/cross-linker contents for oral/topical sustained drug release applications and determined the micromechanical properties by nanoindentation. Compression elastic moduli of materials were calculated by using the limited depth of indentation according to Hertz elastic deformation model and presented as the histogram of multiple data. In terms of drug release practices, poly (VAc-co-DVB) microspheres with a high DVB content, especially in topical applications, are expected to carry drugs under mechanical stresses of less than 1.0 GPa.     

Effects of drug and polymer molecular weight on drug release from PLGA‐mPEG microspheres

This study investigated the effects of drug and polymer molecular weight on release kinetics from poly (g ‐co‐glycolic acid)‐methoxypoly(ethyleneglycol) (PLGA‐mPEG) microspheres. Bovine serum albumin (BSA, 66 kDa), lysozyme (LZ, 13.4 kDa), and vancomycin (VM, 1.45 kDa) were employed as the model drugs, and encapsulated in PLGA‐mPEG microspheres of different molecular weight. Release of macromolecular BSA was mainly dependent on diffusion of drug at/ near the surface of the matrix initially and dependent on degradation of matrix at later stages, while, the small drug of vancomycin seemed to depend totally on diffusion for the duration of the release study. The release behavior of lysozyme was similar to bovine serum albumin, except a shorter lag period. PLGA‐mPEG molecular weight also affected the release behavior of bovine serum albumin and lysozyme, but not obviously. PLGA‐mPEG microspheres in smaller molecular weight seemed to degrade more quickly to obtain a mass lose and matrix erosion, and thus, an accelerated release rate of bovine serum albumin and lysozyme. Vancomycin released much faster than bovine serum albumin and lysozyme, and exhibited no lag period, as it is thought to be diffusion‐controlled. Besides, vancomycin showed no difference in release behavior as PLGA‐mPEG molecular weight change. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41431.