Polymeric Drug Delivery Systems Research Articles

An Approach to 3D Printing Techniques, Polymer Materials, and Their Applications in the Production of Drug Delivery Systems

Three-dimensional printing (3DP) technologies are characterized as a set of innovative manufacturing techniques that allow for the creation of complex and/or personalized three-dimensional physical objects on the work surface of a 3D printing machine (based on the computer-aided design (CAD) project designs of these parts). Three-dimensional printing techniques are widely used in various areas of knowledge, such as education, engineering, and biomedicine. Polymeric materials are widely used for these applications, mainly due to their desirable workability during part manufacturing, compatibility with other chemical materials, the wide range of polymers with different physical and chemical characteristics, and the possibility for recycling. The development of polymeric drug delivery systems (DDSs) by 3D printing is currently an active field of research, both in academia and industry, given the potential of this technique for medical purposes. In this context, this work reviews potential polymers for the production of drug delivery systems via 3D printing techniques. The demonstrations of the main 3DP techniques used for drug delivery applications include their working principles and advantages and how the technologies develop the final product. In addition, potential synthetic and natural polymers that are currently used in 3DP drug delivery devices are presented and discussed based on recent scientific studies.

Sodium Chloride Induced pH and Temperature Responsive Biocompatible Hydrogel of Choline Oleate for Transdermal Drug Delivery of Doxorubicin

AbstractNanodrug carriers have various biological and pharmaceutical applications, and among all the transdermal drug delivery is fascinating, specifically for localized medication therapy to a specific diseased organ or limited diseased area of the body, such as breast cancer cells or carcinoma cells. This way the efficacy of drug can be enhanced and its side effect to other healthy organs can be reduced to great extent. To ameliorate the limitations of traditional polymeric drug delivery systems, such as limited quantity and heterogeneity of the loaded drug, we developed a NaCl induced biocompatible gel of wormlike micelles of surface active ionic liquid (SAIL) i. e. choline oleate ([Ch][Ol]). Apart from the pH and temperature responsive mechanical properties, the designed gel also show good skin permeability, biocompatibility, adhesive qualities, stretchability, and viscoelasticity. The gel was tested for encapsulation of anticancer drug doxorubicin (DOX) and its transdermal delivery at pH=7.4 and pH=5.2. This system exhibits tremendous transdermal permeability of DOX and selective release more amount of the drug at 5.2 pH. Hence for localised and targeted delivery of an anticancer drug, this system can be proven to be suitable.

Ultra-high-performance liquid chromatography with tandem mass spectrometry method for cellular toxicity and pharmacokinetic study of PEG1K polymers.

Polyethylene glycol (PEG) is one of the most commonly used polymers in drug delivery systems. The investigation of the pharmacokinetic behavior of PEG is important for revealing the toxicity and efficiency of PEG-related Nano-drug delivery systems. A high through-put and selective ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method coupled with collision-induced dissociation (CID) in source technique was developed and validated to determine PEG1K polymers in cellular samples in this study. The countless precursor ions of PEG1K are dissociated in the source to generate numerous product ions which have different numbers of subunits. The transition of [M+H]+ precursor ions → product ions at m/z 177.1 (four subunits)→89.1 (two subunits) was selected to determine PEG1K due to its high sensitivity. The UHPLC-MS/MS method coupled with CID in the source showed good linearity over the range of 0.1-10μg/mL. Intra-day and inter-day accuracies and precisions of the assay were all within±12.39%. The assay was successfully applied to a cellular pharmacokinetic study of PEG1K in human breast cancer cells. The cytotoxicity of PEG1K polymers was also studied and the results indicated that the cytotoxicity of PEG1K was not significant in the range of 5-1200μg/mL.

Re-engineering lysozyme solubility and activity through surfactant complexation

Hydrophobic ion-pairing is an established solubility engineering technique that uses amphiphilic surfactants to modulate drug lipophilicity and facilitate encapsulation in polymeric and lipid-based drug delivery systems. For proteins, surfactant complexation...

Anti-cancer activity of capsaicin and its analogs in gynecological cancers.

Capsaicin is the hot and pungent ingredient of chili peppers. It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams. Several convergent studies reveal that capsaicin displays growth-suppressive activity in human cancers in vitro and in vivo. Apart from its growth-suppressive activity (as a single agent), capsaicin has been found to sensitize human cancer cells to the pro-apoptotic effects of chemotherapy and radiation. The first part of this book chapter discusses the anti-cancer activity of capsaicin in gynecological cancers in cell culture experiments and mouse models. Out of all gynecological cancers, the anti-cancer activity of capsaicin (and its analogs) has only been investigated in cervical cancers and ovarian cancers. The clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting. Two strategies have been investigated to overcome these drawbacks of capsaicin. The first is to encapsulate capsaicin in sustained release drug delivery systems. The second strategy is to design non-pungent capsaicin analogs which will retain the anti-tumor activity of capsaicin. The second part of this chapter provides an overview of the anti-neoplastic (and chemosensitization activity) of capsaicin analogs and capsaicin-based sustained release formulations in cervical and ovarian cancers. The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.

A Review on the Role of Polymers in Pharmaceutical Drug Delivery System

Abstract : This review article focuses on polymers of therapeutic agents used in pharmaceuticals. These dosage forms include e.g tablets, patches, tapes, films, semi-solids and powders. As such, polymers are the backbone of pharmaceutical drug delivery systems check the release of the drug from the device. Biodegradable polymers draw attention to its use because they can degrade Based on a biodegradable polymer, non-toxic monomers and, most importantly, a constant drug release rate can be achieved. controlled release device. Natural polymers can be used as a tool to achieve predetermined drug release rates and these Physicochemical properties and easy availability create a platform for its use as a polymer in drug delivery systems. Biodegradable polymers have been widely used in biomedical applications due to their known biocompatibility and biodegradability In the biomedical field, polymers are often used as implants and are expected to function for a long time. These improvements improve the effectiveness of treatment and minimize side effects and other types harm to patients. The main function of the polymer is to protect the drug from the physiological environment and prolong the release of the drug improve its stability. The drug is released from the polymer by diffusion, degradation and swelling. In addition to this review presents Properties and behavior of plant-based and mucoadhesive polymers currently used for drug delivery.

Connected polymeric drug delivery systems: A promise for the future!

Subcutaneous (SC) drug delivery is one of the best routes of drug administration to patients over intravenous (IV) administration due to the ease of application and patient acceptance. The main limitation of using the SC route is administering larger volumes of drug, greater than 3–5 mL for therapeutic dosages. Wearable injectors on body devices are an attractive option for larger-volume drug delivery to patients. Thus, the need for a self-administration strategy at home is growing faster and is required for the next level of time-dependent and high-volume drug delivery. The advances in low-cost, connected on-body delivery systems hold great opportunity for novel ways of delivering home-based drug therapy in the future.

Recent advances in polymeric microparticle-based drug delivery systems for knee osteoarthritis treatment.

Due to the poor bioavailability and high joint clearance of drugs, sustained delivery of therapeutic agents has proven difficult in the treatment of osteoarthritis (OA). Intra-articular (IA) drug delivery strategy is an attractive option for enhancing OA patients' prognosis, for which various polymer materials have been used as drug carriers due to their attractive delivery properties, to slow or even reverse the progress of OA by prolonging the duration of therapeutic agent residence in the joint. This article focuses on the recent developments in natural and synthetic polymer-based microsphere drug delivery systems for treating knee osteoarthritis. It evaluates the translational potential of some novel formulations for clinical application.

Recent Advances in Micro- and Nano-Drug Delivery Systems Based on Natural and Synthetic Biomaterials.

Polymeric drug delivery technology, which allows for medicinal ingredients to enter a cell more easily, has advanced considerably in recent decades. Innovative medication delivery strategies use biodegradable and bio-reducible polymers, and progress in the field has been accelerated by future possible research applications. Natural polymers utilized in polymeric drug delivery systems include arginine, chitosan, dextrin, polysaccharides, poly(glycolic acid), poly(lactic acid), and hyaluronic acid. Additionally, poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable polymers, and bioabsorbable polymers as well as biomimetic and bio-related polymeric systems and drug-free macromolecular therapies have been employed in polymeric drug delivery. Different synthetic and natural biomaterials are in the clinical phase to mitigate different diseases. Drug delivery methods using natural and synthetic polymers are becoming increasingly common in the pharmaceutical industry, with biocompatible and bio-related copolymers and dendrimers having helped cure cancer as drug delivery systems. This review discusses all the above components and how, by combining synthetic and biological approaches, micro- and nano-drug delivery systems can result in revolutionary polymeric drug and gene delivery devices.

Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid)

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

Enzyme-Responsive Branched Glycopolymer-Based Nanoassembly for Co-Delivery of Paclitaxel and Akt Inhibitor toward Synergistic Therapy of Gastric Cancer.

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

Cryo-XPS for Surface Characterization of Nanomedicines.

Nanoparticles used for medical applications commonly possess coatings or surface functionalities intended to provide specific behavior in vivo, for example, the use of PEG to provide stealth properties. Direct, quantitative measurement of the surface chemistry and composition of such systems in a hydrated environment has thus far not been demonstrated, yet such measurements are of great importance for the development of nanomedicine systems. Here we demonstrate the first use of cryo-XPS for the measurement of two PEG-functionalized nanomedicines: a polymeric drug delivery system and a lipid nanoparticle mRNA carrier. The observed differences between cryo-XPS and standard XPS measurements indicate the potential of cryo-XPS for providing quantitative measurements of such nanoparticle systems in hydrated conditions.

Synthesis and properties of novel drug-loaded nano micelles based on Jerusalem Artichoke polysaccharides.

To develop a novel polymeric nano micelle drug delivery system, JAP-based drug-loaded nano micelles (FFC/JAP-HA) were prepared by chemical modification/ultrasound/molecular self-assembly method. The results showed that JAP was connected with hyaluronic acid (HA) by an ester bond, the particle sizes of FFC/JAP-HA were 329.8 ± 2.3 nm, and the critical micelle concentration (CMC) of FFC/JAP-HA was 3.3 × 10−2 mg/mL. The hemolysis results, cytotoxicity test results, and histological results also showed that the FFC/JAP-HA had good biocompatibility. Furthermore, pharmacokinetic results suggested that the retention time (MRTINF_obs) of FFC/JAP-HA could be extended to 918.23 ± 37.25 min, which laid a foundation for the development of a new polymeric nano micelle drug loading system.

Nanomedicines: An approach to treat placental insufficiency and the current challenges.

Preeclampsia and fetal growth restriction are common pregnancy complications that significantly impact perinatal health and offspring development later in life. The origin of these complex syndromes overlap in placental insufficiency. Progress in developing treatments for maternal, placental or fetal health is mainly limited by the risk of maternal and fetal toxicity. Nanomedicines are a promising approach to safely treat pregnancy complications since they can regulate drug interaction with the placenta to enhance efficacy of the treatment while minimizing exposure of the fetus. This narrative review discusses the current developments and challenges of nanomedicines during pregnancy with a focus on preclinical models of placenta insufficiency syndromes. Firstly, we outline the safety requirements and potential therapeutic maternal and placental targets. Secondly, we review the prenatal therapeutic effects of the nanomedicines that have been tested in experimental models of placental insufficiency syndromes. The majority of liposomes and polymeric drug delivery system show promising results regarding the prevention of trans-placental passage nanomedicines in uncomplicated and complicated pregnancies. The others two studied classes, quantum dots and silicon nanoparticles, have been investigated to a limited extent in placental insufficiency syndromes. Characteristics of the nanoparticles such as charge, size, and timing of administration have been shown to influence the trans-placental passage. The few available preclinical therapeutic studies on placental insufficiency syndromes predominantly show beneficial effects of nanomedicines on both maternal and fetal health, but demonstrate contradicting results on placental health. Interpretation of results in this field is complicated by the fact that results are influenced by the choice of animal species and model, gestational age, placental maturity and integrity, and nanoparticle administration route. Nanomedicines form a promising therapeutic approach during (complicated) pregnancies mainly by reducing fetal toxicity and regulating drug interaction with the placenta. Different nanomedicines have been proven to effectively prevent trans-placental passage of encapsulated agents. This can be expected to dramatically reduce risks for fetal adverse effects. Furthermore, a number of these nanomedicines positively impacted maternal and fetal health in animal models for placental insufficiency. Demonstrating that effective drug concentrations can be reached in the target tissue. While these first animal studies are encouraging, more research is needed to better understand the influence of the pathophysiology of this multi-factorial disease before implementation in clinical practice can be considered. Therefore, extensive evaluation of safety and efficacy of these targeted nanoparticles is needed within multiple animal, in vitro, and/or ex vivo models. This may be complemented by diagnostic tools to assess the disease status to identify the best time to initiate treatment. Together these investigations should contribute to building confidence in the safety of nanomedicines for treating mother and child, as safety has, understandably, the highest priority in this sensitive patient groups.

Cyanocobalamin-Modified Colistin-Hyaluronan Conjugates: Synthesis and Bioactivity.

Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 μg/mg vitamin B12 and the CT content was 335 μg/mg; they consisted of particles of two sizes, 98 and 702 nm, with a ζ-potential of approximately -25 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 μg/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30-40% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA-CT-B12 conjugates was 3.5 × 10-6 cm/s, corresponding to an in vivo intestinal absorption of 50-100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties.

A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions.

The eye's intricate anatomical barriers pose significant challenges to the penetration, residence time, and bioavailability of topically applied medications, particularly in managing uveitis and neuro-ophthalmologic conditions. Addressing this issue, polymeric nano-based drug delivery systems (DDS) have surfaced as a promising solution. These systems enhance drug bioavailability in hard-to-reach target tissues, extend residence time within ocular tissues, and utilize biodegradable and nanosized polymers to reduce undesirable side effects. Thus, they have stimulated substantial interest in crafting innovative treatments for uveitis and neuro-ophthalmologic diseases. This review provides a comprehensive exploration of polymeric nano-based DDS used for managing these conditions. We discuss the present therapeutic hurdles posed by these diseases and explore the potential role of various biopolymers in broadening our treatment repertoire. Our study incorporates a detailed literature review of preclinical and clinical studies from 2017 to 2023. Owing to advancements in polymer science, ocular DDS has made rapid strides, showing tremendous potential to revolutionize the treatment of patients with uveitis and neuro-ophthalmologic disorders.

A review of thermoresponsive drug delivery systems based on LCST/UCST polymer nanofibers

Drug delivery systems and thermoresponsive polymers are garnering more interest due to technological advancement. The synthesis, characteristics, and uses of stimuli-responsive polymers in drug delivery systems are discussed in this paper. LCST and UCST polymers, two subtypes of thermoresponsive polymers, are also discussed, along with their processes and biomedical applications. The paper also discusses the use of conventional nanofibers and stimuli-responsive nanofibers for drug delivery systems and the most recent developments in electrospinning technology. The article also analyses the difficulties facing drug delivery systems today. This paper makes the case that novel electrospinning technologies must be developed in addition to further research into drug delivery systems based on UCST polymers with strong biocompatibility and biodegradability.

Interplay between Diffusion and Bond Cleavage Reaction for Determining Release in Polymer-Drug Conjugates.

In conjugated polymeric drug delivery systems, both the covalent bond degradation rate and the diffusion of the freely moving drug particles affect the release profile of the formulation. Using Monte Carlo simulations in spherical matrices, the release kinetics resulting from the competition between the reaction and diffusion processes is discussed. For different values of the relative bond cleavage rate, varied over four orders of magnitude, the evolution of (i) the number of bonded drug molecules, (ii) the fraction of the freely moved detached drug within the polymer matrix, and (iii) the resulting fractional release of the drug is presented. The characteristic release time scale is found to increase by several orders of magnitude as the cleavage reaction rate constant decreases. The two extreme rate-limiting cases where either the diffusion or the reaction dominates the release are clearly distinguishable. The crossover between the diffusion-controlled and reaction-controlled regimes is also examined and a simple analytical formula is presented that can describe the full dependence of the release time on the bond cleavage rate constant. This simple relation is provided simply by the sum of the characteristic time for purely diffusional release and the bond cleavage decay time, which equals the inverse of the reaction rate constant.

Research Progress of a Pesticide Polymer-Controlled Release System Based on Polysaccharides.

In recent years, with the development of the nanomaterials discipline, many new pesticide drug-carrying systems-such as pesticide nano-metal particles, nano-metal oxides, and other drug-carrying materials-had been developed and applied to pesticide formulations. Although these new drug-loading systems are relatively friendly to the environment, the direct exposure of many metal nanoparticles to the environment will inevitably lead to potential effects. In response to these problems, organic nanomaterials have been rapidly developed due to their high-quality biodegradation and biocompatibility. Most of these organic nanomaterials were mainly polysaccharide materials, such as chitosan, carboxymethyl chitosan, sodium alginate, β-cyclodextrin, cellulose, starch, guar gum, etc. Some of these materials could be used to carry inorganic materials to develop a temperature- or pH-sensitive pesticide drug delivery system. Herein, the pesticide drug-carrying system developed based on polysaccharide materials, such as chitosan, was referred to as the pesticide polymer drug-carrying system based on polysaccharide materials. This kind of drug-loading system could be used to protect the pesticide molecules from harsh environments, such as pH, light, temperature, etc., and was used to develop the function of a sustained release, targeted release of pesticides in the intestine of insects, and achieve the goal of precise application, reduction, and efficiency of pesticides. In this review, the recent progress in the field of polysaccharide-based polymer drug delivery systems for pesticides has been discussed, and suggestions for future development were proposed based on the current situation.

3D Printing Technology as a Promising Tool to Design Nanomedicine-Based Solid Dosage Forms: Contemporary Research and Future Scope.

3D printing technology in medicine is gaining great attention from researchers since the FDA approved the first 3D-printed tablet (Spritam®) on the market. This technique permits the fabrication of various types of dosage forms with different geometries and designs. Its feasibility in the design of different types of pharmaceutical dosage forms is very promising for making quick prototypes because it is flexible and does not require expensive equipment or molds. However, the development of multi-functional drug delivery systems, specifically as solid dosage forms loaded with nanopharmaceuticals, has received attention in recent years, although it is challenging for formulators to convert them into a successful solid dosage form. The combination of nanotechnology with the 3D printing technique in the field of medicine has provided a platform to overcome the challenges associated with the fabrication of nanomedicine-based solid dosage forms. Therefore, the major focus of the present manuscript is to review the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology. Utilization of 3D printing techniques in the field of nanopharmaceuticals achieved the successful transformation of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) to solid dosage forms such as tablets and suppositories easily with customized doses as per the needs of the individual patient (personalized medicine). Furthermore, the present review also highlights the utility of extrusion-based 3D printing techniques (Pressure-Assisted Microsyringe-PAM; Fused Deposition Modeling-FDM) to produce tablets and suppositories containing polymeric nanocapsule systems and SNEDDS for oral and rectal administration. The manuscript critically analyzes contemporary research related to the impact of various process parameters on the performance of 3D-printed solid dosage forms.