Alkyl pectin: Hydrophobic matrices for controlled drug release

Alkyl pectin with various fatty acid (C₄–C₁₆) bromides increased its hydrophobic characteristic and made important changes in its structural features. Unmodified pectin exhibited a low degree of order (DO) and a weak tablet‐crushing strength. Pectin alkylated with a short chain length (C₄) possessed similar properties but exhibited significant swelling. Alkylation with longer side chains (C₈–C₁₆) resulted in a higher DO and crushing strength but a lower swelling. The best mechanical characteristics and drug‐release properties were found for octanoyl pectin (OP; degree of substitution = 7.06–15.41%) tablets with 20% bovine serum albumin as a tracer. The high stability of these monolithic tablets appeared to be due to hydrophobic interactions between side chains, as shown by a more organized structure. IR spectroscopy and differential scanning calorimetry analyses of OP were consistent with a hydrophobic self‐assembling model. The drug dissolution kinetics showed longer release times for higher degrees of functionalization, that is, 35 h (for 10.88% substitution) and 80 h (for 15.41% substitution); this suggested OP excipients as interesting candidates for oral and subdermal pharmaceutical applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41302.     

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.     

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     

Stimuli-responsive hybrid microgels for controlled drug delivery: Sorafenib as a model drug

Microgels (MGs) are synthetic colloidal hydrogel particles made of three dimensional polymer networks. Their chemical composition is crucial for their use as intelligent drug release systems operated by temperature control. Herein, several MGs using N-isopropylacrylamide (Nipam)/N-isopropylmethacrylamide (Nipmam), chitosan and acrylic/methacrylic acid have been synthesized by free radical polymerization reactions (NC MGs) and the effects of surfactants and different reaction times on size and swelling properties have been investigated. MGs have been identified and characterized by dynamic light scattering and atomic force microscopy, and finally used to optimize the encapsulation protocol of the hydrophobic drug sorafenib. The drug delivery system here described has encapsulation efficiency of 40% and releases 10% of the entrapped drug over about 16 h after the temperature is raised above the volume phase transition temperature. Data suggest that MGs with optimized composition may act as properly instructed entities able to trap and release biomolecules following external stimuli.     

Rosin derivatives: novel film forming materials for controlled drug delivery

Two new rosin derivatives (RD-1 and RD-2) were synthesized in the laboratory and evaluated for physicochemical properties, molecular weight (M_w), polydispersity (M_w/M_n) and glass transition temperature (T_g). Plasticizer free films of the derivatives were produced by casting/solvent evaporation method. The surface morphology (SEM), water vapour transmission and mechanical properties (tensile strength, percent elongation and modulus of elasticity) of the films were investigated. The derivatives were further evaluated for pharmaceutical film coating by characterizing the release of a model drug (diclofenac sodium) from non-pariel seeds (pellets) coated with the derivatives. Pellet film coating could be achieved without agglomeration of the pellets within a reasonable operation time. Drug release from the coated pellets was sustained up to 10 h with the two rosin derivatives. These findings suggest the possible application of rosin derivatives (RD-1 and RD-2) for film coating.     

Development of functional mesoporous microparticles for controlled drug delivery

Mesoporous microbeads can be easily obtained by radical polymerization of biocompatible glycerol dimethacrylate (GDMA) in supercritical carbon dioxide. Small mass density microparticles (ρ = 0.19-0.37 g cm⁻³) with controlled size (1-3 μm) and homogeneous morphology are obtained by the addition of different stabilizers to the polymerization media. The microbeads were obtained in quantitative yield as white, dry powders directly from the reaction vessel possessing a pollen-like morphology. The (S)-ibuprofen loading (up to 120 mg g⁻¹) and release profile from the PGDMA microbeads is highly promising which makes them potential drug delivery vehicles.     

Ethyl methacrylate grafted on two starches as polymeric matrices for drug delivery

The use of copolymers grafted on starch for controlled‐release technology is an interesting proposal, since a modification of a natural polymer is more suitable than synthetic polymers because of its biocompatibility and biodegradability. The aim of this paper is to synthesize acrylic polymers grafted on carbohydrates to investigate the release kinetic of different solubility drugs from polymeric matrix systems and to observe the effect of grafted copolymers and drug solubility on the release mechanism. Copolymer variables such as carbohydrate content, stereoregularity of grafted chains, particle size, morphology, sensitivity to hydration, and rheological properties are discussed. Tablets were prepared by direct compression of the graft copolymer and drug. The drugs' release in vitro kinetics was studied by dissolution testing. Drug release from tablets depends on polymer matrix, polymer content, drug, and pH. An increase in drug solubility results in an increase in the rate of dissolution, as in the case of a poor hydrophilic matrix. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 523–536, 2005     

Thermoresponsive and acid-cleavable amphiphilic copolymer micelles for controlled drug delivery

Thermoresponsive and acid-cleavable amphiphilic block copolymers poly(N-isopropylacrylamide)-acetal-poly(4-substituted-ε-caprolactones) (PNiPAAm-a-PXCLs) containing an acidic-cleavable acetal linkage at the junction between the temperature-sensitive hydrophilic PNiPAAm and the degradable hydrophobic block PXCL were synthesized through ring-opening polymerization and electrophilic addition reactions. These polymer solutions showed reversible changes in optical properties and a lower critical solution temperature in the range of 32.0–46.4°C. The copolymers formed micelles in aqueous solution with critical micelle concentrations in the range of 0.83–15.95?mg?L^?1 had hydrodynamic sizes of <200?nm and were spherical. Under the combined stimulation of temperature and pH, the micellar nanoparticles could be dissociated; the loaded molecules could be released from the assemblies more efficiently than that under only one stimulus or without stimulus. In addition, the nanoparticles exhibited low toxicity against human cervical cancer (HeLa) cells at concentrations ≤1000?µg?mL^?1. Doxorubicin-loaded PNiPAAm₁₁-a-PCL₂₈ micelles also effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration (IC₅₀) of 1.60?µg?mL^?1.     

Rapid and efficient sprayed multilayer films for controlled drug delivery

The speed and scalability of film fabrication can dictate the translation of technologies from the laboratory scale to industrial level mass production. Spray‐assisted layer‐by‐layer (LbL) film assembly enables the rapid coating of geometrically complex and porous substrates with functional polyelectrolyte multilayers. Unfortunately, the encapsulation efficiency can be as low as one percent, making this technique prohibitively costly with even modestly priced materials. Herein, we used containment chambers to separately capture the aerosolized solutions for each step in the spray‐LbL process and analyzed the effect of recycling on multilayer film assembly. With potential biomedical applications, we studied the controlled release films of (Poly 2/heparin/lysozyme/heparin)_n films and tracked the distribution of lysozyme after film assembly. In a “Conventional” Spray‐LbL protocol, only 6% of the aerosolized lysozyme is incorporated into the film. By collecting and returning the expended solutions to their respective reservoirs (Recycle Spray‐LbL), we increased this efficiency to 15%. We also tuned the final distribution of lysozyme by adjusting the spray times (Optimized Spray‐LbL), which minimized the amount of lysozyme lost to non‐specific adsorption and reduced the fraction of lysozyme lost to the wash step from 30% and 75% (Conventional and Recycle Spray‐LbL, respectively) to 13%. Despite the changes in film assembly parameters, each film demonstrated similar controlled release properties. With the inherent limitations of time and cost facing Dip and Conventional Spray‐LbL technologies, respectively, the implementation of recycling to the latter demonstrates improvements in efficiency and time that may make it more attractive for the manufacture of biomedical coatings. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43563.     

Redox- and pH-responsive hydrogels: formulation and controlled drug delivery

A novel drug-delivery carrier, poly(ethylene glycol) methyl ether methacrylate/2-(diethylamino) ethyl methacrylate/bis (2-methacryloxyethyl) disulfide (PEDS) hydrogel, was prepared with poly(ethylene glycol) methyl ether methacrylate (PEGMA) and amine containing 2-(diethylamino)ethyl methacrylate (DMAEMA) monomers and a disulfide-containing cross-linking agent bis(2-methacryloxyethyl) disulfide (DSDMA). The RN(C₂H₅)₂ in poly(2-(diethylamino)ethyl methacrylate) (PDMAEMA) can be protonated in acidic environments, causing the expansion of the polymer network and promotion of drug release. The presence of the biologically available reducing agent glutathione (GSH) induces disulfide bond cleavage in DSDMA, which initiates the expansion of the polymer networks. The inner morphology dependence on redox and pH conditions for PEDS₁ hydrogels was revealed. In neutral solutions without GSH, a pore structure with full, thick walls was observed. In acidic or GSH solutions, the pore structure was destroyed, and the pore cell walls were thin or broken. These changes can induce drug release. Drug release studies were also conducted using berberine as a model drug. The drug released from the hydrogels into the supernatant was measured in both GSH and acidic solutions. PEDS₁ hydrogels exhibited a substantial enhancement in release rates in acidic solutions or neutral GSH solutions, suggesting the drug release from PEDS hydrogels is redox- and pH-dependent.     

A fast pH-responsive IPN hydrogel: Synthesis and controlled drug delivery

A series of fast pH-responsive silk sericin (SS)/poly(methacrylic acid) (PMAA) IPN hydrogels were prepared by the simultaneous-IPN method. The structure of the resultant IPN hydrogels was characterized by fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling experimental of the IPNs revealed that the hydrogels displayed definite pH sensitivity under physiological conditions, as well as sharp changes in the mesh size of their network as a function of the composition and pH of the swelling media. Bovine serum albumin (BSA) was chosen as a model protein to evaluate the permeation profile through the IPNs in both the simulated gastric and intestinal pH conditions. In all cases, it was found that the release rate of BSA was lower in acidic media (pH 2.6) and higher in basic media (pH 7.4).     

Preparation of polymer nanoparticles loaded with doxorubicin for controlled drug delivery

The preparation of polymer nanoparticles loaded with an active principle, commonly used in cancer treatment, is investigated here from the experimental point of view. The main novelty of this work stands in the use of continuous confined impinging jets mixers in combination with realistic materials, notably the biodegradable and biocompatible copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) together with two forms of the drug doxorubicin. To our knowledge this is the first attempt to use for such a system a device that can be operated continuously and can be easily scaled up. Nanoparticles are produced via solvent-displacement experimenting different solvents; the effect of the other operating parameters is also investigated. Nanoparticles are characterized in terms of their size distribution and surface properties; for a limited number of samples prepared with the optimized preparation protocol further characterization (in terms of drug loading, incorporation and release profiles) is also carried out. Collected results show that the overall approach is capable of producing nanoparticles with controlled particle size distribution, drug loading and good reproducibility and that on the contrary of what reported in the literature the presence of the active principle does play an important role.     

Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.     

Development of interpenetrating polymeric network for controlled drug delivery and its evaluation

Abstract

Polymers play vital role in drug delivery systems. Aim of current research work was to elucidate the effect of Hydroxyethyl cellulose (HEC), acrylic acid (AA) and N'N'-methylene bis-acrylamide (MBA) in formulation of pH sensitive nexus for targeted delivery of acid sensitive drug perindopril erbumine (PE). Different feed ratios were employed to prepare nexus via free radical polymerization. FTIR (Fourier transform infrared spectroscopy) depicts efficient grafting. Thermal parameters (DSC, DTA and TGA) were thermodynamically stable and morphological (SEM) analysis represented porous architecture. pH sensitivity was supported by on-off switching in acid and basic media. Hence, HEC-co-AA based design was encouraging for targeted delivery of perindopril erbumine.     

PEGylated hollow pH‐responsive polymeric nanocapsules for controlled drug delivery

Novel pH‐responsive PEGylated hollow nanocapsules (HNCaps) were fabricated through a combination of distillation–precipitation copolymerization and surface thiol–ene ‘click’ grafting reaction. For this purpose, SiO₂ nanoparticles were synthesized using the Stöber approach, and then modified using 3‐(trimethoxysilyl)propyl methacrylate (MPS). Afterward, a mixture of triethyleneglycol dimethacrylate (as crosslinker), acrylic acid (AA; as pH‐responsive monomer) and MPS‐modified SiO₂ nanoparticles (as sacrificial template) was copolymerized using the distillation–precipitation approach to afford SiO₂@PAA core–shell nanoparticles. The SiO₂ core was etched from SiO₂@PAA using HF solution, and the obtained PAA HNCaps were grafted with a thiol‐end‐capped poly(ethylene glycol) (PEG) through a thiol–ene ‘click’ reaction to produce PAA‐g‐PEG HNCaps. The fabricated HNCaps were loaded with doxorubicin hydrochloride (DOX) as a model anticancer drug, and their drug loading and encapsulation efficiencies as well as pH‐dependent drug release behavior were investigated. The anticancer activity of the drug‐loaded HNCaps was extensively evaluated using MTT assay against human breast cancer cells (MCF7). The cytotoxicity assay results as well as superior physicochemical and biological features of the fabricated HNCaps mean that the developed DOX‐loaded HNCaps have excellent potential for cancer chemotherapy. © 2020 Society of Chemical Industry     

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.     

Dual-sensitive and folate-conjugated mixed polymeric micelles for controlled and targeted drug delivery

For this study, we prepared a new type of drug carrier with the characteristics of stimuli-responsive transition and tumor-specific recognition through the co-assembly of two series of amphiphilic block copolymers, poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-methacryloyl caproic acid] and poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-(2-(methacrylamido)ethyl) folatic amide]. The pH-dependent thermal transition and the content of the targeting ligands of the mixed polymeric micelles are well correlated with the chemical structures and compositions of these two copolymers. Doxorubicin-loaded mixed polymeric micelles are stable at body temperature in the neutral condition for prolonged circulation in blood vessels, and demonstrated rapid drug release at acidic pH levels. The cumulative drug release profiles showed a relatively slow release at pH 7.4, and a quick release of 85% in 3 h at pH 5.3. The cytotoxicity tests against FA-positive (HeLa) and FA-negative (HT-29) tumor cell lines suggest that this mixed polymeric micelle system has potential merits as a controlled and targeted drug delivery system.     

One pot preparation of polyurethane-based GSH-responsive core-shell nanogels for controlled drug delivery

In this work, we present a new type of glutathione (GSH)-responsive polyurethane-based core‑shell nanogels (RS-CS-PUNGs) with hydrophilic methoxypolyethylene glycols (mPEG) shell, which was prepared by a one-pot synthetic method. The obtained RS-CS-PUNGs not only show a good size distribution with the hydrodynamic radii around of 20 nm, but also exhibit good stability in the organic solvent. The results demonstrate that GSH (10 mM) trigger the nanogel swelling and accelerate the loaded drug release in PBS (pH = 7.4). Although the RS-CS-PUNGs loaded with DOX show a slower cellular uptake behavior than the free doxorubicin (DOX), which is likely caused by the controlled drug release property of the nanocarrier, the enhanced cellular uptake fluorescence intensity of RS-CS-PUNGs loaded with DOX is still observed compared to the control group. Both MTT and CCK-8 assay indicate that although an obvious lower initial cytotoxicity is observed compared to free DOX at 24 h postincubation, the cytotoxicity of the RS-CS-PUNGs loaded with DOX is obvious enhanced after treated 72 h, which stayed at the similar level with free DOX. Attributing to the easy preparation progress and GSH-responsive property, RS-CS-PUNGs maybe hold the potential for further application in the field of drug delivery. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48473.     

Poly(L-lactide-co-caprolactone)/collagen electrospun mat: Potential for wound dressing and controlled drug delivery

Here we report a novel bioactive electrospun mat based on poly(L-lactide-co-caprolactone) (PLLC) and collagen for wound dressing and sustained drug delivery of gentamicin. PLLC/collagen electrospun mat loaded with 10% gentamicin showed bioactivity for 15 days against Gram-positive and Gram-negative bacteria. The in vitro cell culture of 3T3 fibroblasts confirmed that these electrospun mat provide an increased specific interface area and hydrophilicity to enhance cell attachment, proliferation, and migration. The modified PLLC/collagen mat provided an excellent enhancement in properties of antibacterial wound dressings with a minimum in vitro toxicity and high potency for promoting wound healing stages.