Polymer-based Drug Delivery Research Articles

Synthetic and Natural Polymers Enhancing Drug Delivery and Their Treatment: A Comprehensive Review

Polymers, both synthetic and natural, play a critical role in modern drug delivery systems by enhancing the efficacy, targeting, and release profiles of therapeutic agents. This comprehensive review delves into the various types of synthetic polymers such as poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and polyvinyl alcohol (PVA), as well as natural polymers like chitosan, alginate, and gelatin. These polymers are explored for their potential to improve solubility, bioavailability, and controlled release of drugs. Moreover, their application in targeted drug delivery, particularly for cancer, cardiovascular, and inflammatory diseases, is highlighted. The review also compares the advantages and limitations of synthetic versus natural polymers, discussing their biodegradability, biocompatibility, and regulatory considerations. Advances in polymer-based drug delivery platforms such as nanoparticles, hydrogels, and micelles are also examined, offering insights into future directions in personalized medicine. The highlights of provide in the review article, initially basics of drug delivery, polymer, polymerization with role of polymer in polymerization. At intermediate, classification, sources of polymer with that some advanced approached in drug delivery and lastly, marketed, recent available products with future challenges and current status in the drug delivery. Keywords: Biodegradable polymer; natural; compatible; drug delivery; treatment; enhancing; polymers.

Role of Natural Polymers in Novel Drug Delivery Systems

Natural polymers have gained significant attention in the field of drug delivery due to their inherent biocompatibility, biodegradability, and low toxicity. This review article aims to provide a comprehensive overview of the diverse roles that natural polymers play in the development of novel drug delivery systems. Beginning with a classification of natural polymers based on their origin (plant, animal, microbial), we explore their unique characteristics and advantages over synthetic counterparts. The review discusses the pivotal role of natural polymers in formulating various drug delivery systems, including sustained/controlled release formulations, targeted delivery platforms, mucoadhesive systems, and nanotechnology-based approaches. Techniques such as emulsification, ionotropic gelation, coacervation, and electrospinning for natural polymer-based drug delivery are elucidated, highlighting their versatility and applicability across different administration routes. Furthermore, we delve into the diverse applications of natural polymers in drug delivery, encompassing oral, transdermal, ocular, injectable, nasal, buccal, and vaginal delivery routes. Recent advances and innovations in combining natural polymers with synthetic counterparts, incorporating stimuli-responsive properties, and personalized medicine approaches are also explored. Despite the numerous advantages offered by natural polymers, challenges such as variability in polymer properties, standardization issues, scale-up challenges, and regulatory considerations are discussed. The review concludes with future perspectives, highlighting emerging trends and opportunities for further research and development in the field of natural polymer-based drug delivery systems. Overall, this review provides valuable insights into the pivotal role of natural polymers in advancing drug delivery technology, paving the way for safer, more efficient, and patient-friendly therapeutic interventions.

Recent Advances and Future Prospects in Polymer-Mediated Drug Delivery Systems: A Comprehensive Review.

Polymer-based drug carriers have revolutionized the pharmaceutical landscape, providing innovative approaches for efficient drug delivery. These advanced systems have significantly mitigated traditional challenges, offering new avenues for targeted and controlled drug release. This paper aims to explore polymers, focusing on their classification, properties, drug release mechanisms, and pharmaceutical applications while emphasizing recent advancements and future prospects in the field. Polymers can be classified based on their origin, biodegradability, and physical properties. Their unique characteristics, such as biocompatibility, flexibility, and ability to modify surface properties, make them ideal for drug delivery applications. The review delves into various drug release mechanisms employed by polymer-based systems, including diffusion, degradation, swelling, and stimuli-responsive release. These mechanisms ensure a controlled and sustained release of therapeutic agents, enhancing efficacy and reducing side effects. The pharmaceutical applications of polymer-based drug carriers are vast, encompassing targeted delivery to specific tissues or cells, sustained-release formulations, and the delivery of complex molecules like proteins and nucleic acids. Despite their advantages, polymer-based drug delivery systems face limitations, including potential toxicity, stability issues, and manufacturing challenges. Addressing these limitations through continued research and development is crucial for advancing the field. Recent advancements, such as smart polymers and nanotechnology integration, hold promise for overcoming these challenges and improving drug delivery efficiency. In conclusion, polymer-mediated drug delivery systems represent a significant leap forward in pharmaceutical technology. This review highlights the importance of polymers in modern medicine, their potential to revolutionize drug delivery, and the ongoing efforts to optimize their use in clinical applications.

The Role of Surface Energy and Wettability in Polymer-Based Drug Delivery Systems: Enhancing Bioadhesion and Drug Release Efficiency

Polymer-based drug delivery systems are pivotal in advancing the precision and efficacy of modern therapeutics. Among the key factors influencing these systems, surface energy and wettability are crucial in determining their interaction with biological tissues and drug release behavior. Surface energy, which governs the adhesive properties of the polymers, plays a significant role in bioadhesion—a critical aspect for drug delivery routes that require prolonged contact with biological surfaces, such as mucosal membranes. Wettability, the extent to which a polymer surface can be wetted by biological fluids, influences both drug loading efficiency and release kinetics. Hydrophilic polymers, characterized by high wettability, typically facilitate rapid drug release, whereas hydrophobic polymers, with low wettability, offer controlled, prolonged release profiles. Additionally, the balance between hydrophilicity and hydrophobicity is essential for optimizing drug-polymer interactions, particularly in systems designed for sustained or targeted drug delivery. Advances in surface modification techniques have enabled precise control over these parameters, allowing for the customization of polymers to meet specific therapeutic requirements. This review discusses the interplay between surface energy, wettability, and drug delivery performance, highlighting how these properties have been manipulated to enhance bioadhesion, drug retention, and release profiles. The review also addresses the challenges in designing polymer wettability, such as maintaining stability, scalability, and regulatory compliance. Finally, it explores emerging trends, including stimuli-responsive polymers and nanotechnology integration, which hold promise for the next generation of drug delivery systems that are more efficient, targeted, and patient-specific, than current systems.

Adapting Ferritin, a Naturally Occurring Protein Cage, to Modulate Intrinsic Agonism of OX40.

Ferritin is a multivalent, self-assembling protein scaffold found in most human cell types, in addition to being present in invertebrates, higher plants, fungi, and bacteria, that offers an attractive alternative to polymer-based drug delivery systems (DDS). In this study, the utility of the ferritin cage as a DDS was demonstrated within the context of T cell agonism for tumor killing. Members of the tumor necrosis factor receptor superfamily (TNFRSF) are attractive targets for the development of anticancer therapeutics. These receptors are endogenously activated by trimeric ligands that occur in transmembrane or soluble forms, and oligomerization and cell-surface anchoring have been shown to be essential aspects of the targeted agonism of this receptor class. Here, we demonstrated that the ferritin cage could be easily tailored for multivalent display of anti-OX40 antibody fragments on its surface and determined that these arrays are capable of pathway activation through cell-surface clustering. Together, these results confirm the utility, versatility, and developability of ferritin as a DDS.

Polymer-Based Drug Delivery Systems for Cancer Therapeutics.

Chemotherapy together with surgery and/or radiotherapy are the most common therapeutic methods for treating cancer. However, the off-target effects of chemotherapy are known to produce side effects and dose-limiting toxicities. Novel delivery platforms based on natural and synthetic polymers with enhanced pharmacokinetic and therapeutic potential for the treatment of cancer have grown tremendously over the past 10 years. Polymers can facilitate selective targeting, enhance and prolong circulation, improve delivery, and provide the controlled release of cargos through various mechanisms, including physical adsorption, chemical conjugation, and/or internal loading. Notably, polymers that are biodegradable, biocompatible, and physicochemically stable are considered to be ideal delivery carriers. This biomimetic and bio-inspired system offers a bright future for effective drug delivery with the potential to overcome the obstacles encountered. This review focuses on the barriers that impact the success of chemotherapy drug delivery as well as the recent developments based on natural and synthetic polymers as platforms for improving drug delivery for treating cancer.

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

Cascade-responsive size/charge bidirectional-tunable nanodelivery penetrates pancreatic tumor barriers.

The pancreatic tumor microenvironment presents multiple obstacles for polymer-based drug delivery systems, limiting tumor penetration and treatment efficacy. Here, we engineer a hyaluronidase/reactive oxygen species cascade-responsive size/charge bidirectional-tunable nanodelivery (btND, G/R@TKP/HA) for co-delivery of gemcitabine and KRAS siRNA, capable of navigating through tumor barriers and augmenting anticancer efficiency. When penetrating the tumor stroma barrier, the hyaluronic acid shell of the nanodelivery undergoes degradation by hyaluronidase in an extracellular matrix, triggering size tuning from large to small and charge tuning from negative to positive, thereby facilitating deeper penetration and cellular internalization. After endocytosis, the nanodelivery protonizes in the endo/lysosome, prompting rapid endo/lysosomal escape, effectively overcoming the lysosome barrier. Intracellular ROS further disrupt the nanodelivery, inducing its size tuning again from small to large and a positive charge decrease for high tumor retention and controlled drug release. The btND shows remarkable antitumor activity in pancreatic cancer mouse models, highlighting the efficacy of this approach in penetrating tumor barriers and enhancing anticancer outcomes.

Self-Report Amphiphilic Polymer-Based Drug Delivery System with ROS-Triggered Drug Release for Osteoarthritis Therapy.

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 μg mL-1 CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.

An overview of nanofibers and microfibers for improved oral delivery of medicines: Challenges and advances

Nanofibers and microfibers are polymer-based drug delivery systems commonly fabricated through the electrospinning technique. They can be fabricated using natural, synthetic, or hybrid polymers. Electrospun nanofibers and microfibers are capable of incorporating various types of active ingredients for drug delivery through different routes of administration. The application of nanofibers and microfibers as oral drug delivery systems is promising as a solubility promoter and for enhancing the rate and extent of bioavailability of poorly water-soluble drugs. These delivery systems exhibit high entrapment efficiency for both hydrophilic and hydrophobic drugs. Additionally, they offer drug protection against the harsh gastrointestinal environment and enable controlled drug release profiles, including immediate burst release, sustained release, biphasic release, pulsatile release, and smart stimuli-responsive drug release. Furthermore, electrospun nanofibers have been utilized as fast-dissolving and gastro-retentive (floating) oral drug delivery systems. Consequently, it appears that fiber technologies, especially nanofibers, with enhanced specific surface area and high encapsulation efficiency, hold promise as drug delivery systems for targeted oral delivery purposes.

Polymer-Based Self-Assembled Drug Delivery Systems for Glaucoma Treatment: Design Strategies and Recent Advances.

Glaucoma has become the world's leading cause of irreversible blindness, and one of its main characteristics is high intraocular pressure. Currently, the non-surgical drug treatment scheme to reduce intraocular pressure is a priority method for glaucoma treatment. However, the complex and special structure of the eye poses significant challenges to the treatment effect and safety adherence of this drug treatment approach. To address these challenges, the application of polymer-based self-assembled drug delivery systems in glaucoma treatment has emerged. This review focuses on the utilization of polymer-based self-assembled structures or materials as important functional and intelligent carriers for drug delivery in glaucoma treatment. Various drug delivery systems, such as eye drops, hydrogels, and contact lenses, are discussed. Additionally, the review primarily summarizes the design strategies and methods used to enhance the treatment effect and safety compliance of these polymer-based drug delivery systems. Finally, the discussion delves into the new challenges and prospects of employing polymer-based self-assembled drug delivery systems for the treatment of glaucoma.

Electrically Controlled Vasodilator Delivery from PEDOT/Silica Nanoparticle Modulates Vessel Diameter in Mouse Brain.

Vascular damage and reduced tissue perfusion are expected to majorly contribute to the loss of neurons or neural signals around implanted electrodes. However, there are limited methods of controlling the vascular dynamics in tissues surrounding these implants. This work utilizes conducting polymer poly(ethylenedioxythiophene) and sulfonated silica nanoparticle composite (PEDOT/SNP) to load and release a vasodilator, sodium nitroprusside, to controllably dilate the vasculature around carbon fiber electrodes (CFEs) implanted in the mouse cortex. The vasodilator release is triggered via electrical stimulation and the amount of release increases with increasing electrical pulses. The vascular dynamics are monitored in real-time using two-photon microscopy, with changes in vessel diameters quantified before, during, and after the release of the vasodilator into the tissues. This work observes significant increases in vessel diameters when the vasodilator is electrically triggered to release, and differential effects of the drug release on vessels of different sizes. In conclusion, the use of nanoparticle reservoirs in conducting polymer-based drug delivery platforms enables the controlled delivery of vasodilator into the implant environment, effectively altering the local vascular dynamics on demand. With further optimization, this technology could be a powerful tool to improve the neural electrode-tissue interface and study neurovascular coupling.

Plasma Modification Techniques for Natural Polymer-Based Drug Delivery Systems.

Natural polymers have attracted significant attention in drug delivery applications due to their biocompatibility, biodegradability, and versatility. However, their surface properties often limit their use as drug delivery vehicles, as they may exhibit poor wettability, weak adhesion, and inadequate drug loading and release. Plasma treatment is a promising surface modification technique that can overcome these limitations by introducing various functional groups onto the natural polymer surface, thus enhancing its physicochemical and biological properties. This review provides a critical overview of recent advances in the plasma modification of natural polymer-based drug delivery systems, with a focus on controllable plasma treatment techniques. The review covers the fundamental principles of plasma generation, process control, and characterization of plasma-treated natural polymer surfaces. It discusses the various applications of plasma-modified natural polymer-based drug delivery systems, including improved biocompatibility, controlled drug release, and targeted drug delivery. The challenges and emerging trends in the field of plasma modification of natural polymer-based drug delivery systems are also highlighted. The review concludes with a discussion of the potential of controllable plasma treatment as a versatile and effective tool for the surface functionalization of natural polymer-based drug delivery systems.

Outcomes of Frontal Sinus Stenting With Steroid Impregnated Microsponge Versus Steroid-Eluting Implant.

Mometasone-eluting poly-L-lactide-coglycolide (MPLG) is available commercially for frontal sinus ostium (FSO) stenting. An alternative chitosan polymer-based drug delivery microsponge is also available at a lower cost per unit. To compare the outcomes of MPLG stents versus triamcinolone-impregnated chitosan polymer (TICP) microsponge in frontal sinus surgery. Patients who underwent endoscopic sinus surgery from December 2018 to February 2022 were reviewed to identify those with the intraoperative placement of TICP microsponge or MPLG stent in the FSO. FSO patency was evaluated by endoscopy at follow-up. Twenty-two-item sinonasal outcome test (SNOT-22) was also recorded, and complications were noted. A total of 68 subjects and 96 FSOs were treated. TICP was first used in August 2021 and MPLG in December 2018. MPLG placement in a Draf 3 cavity was excluded since TICP had not been used during Draf 3 procedure. Both cohorts (TICP 20 subjects, 35 FSOs; MPLG 26 subjects, 39 FSOs) had similar clinical characteristics. At a mean total follow-up of 249.2 days for TICP and 490.4 days for MPLG, FSO patency was 82.9% and 87.1%, respectively (P = .265). At an equivalent follow-up of 130.6 days in TICP and 154.0 days in MPLG, patency was 94.3% and 89.7%, respectively (P = .475). Both groups showed significant reductions in SNOT-22 (P < .001). MPLG demonstrated crusting within the FSO at 1 month (none in TICP). FSO patency for both stents was similar, although TICP had significantly lower costs per unit. Additional comparative trials may be helpful for guiding clinicians on the appropriate clinical situations for the use of these devices.

Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System.

Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications.

Abstract 5261: Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression

Abstract Prostate cancer is the most common cancer in men. Commensurate with risk, current approaches to localized prostate cancer include prostatectomy, prostate radiation with or without radiation therapy or active surveillance. Recent data suggest that systemic anti-androgen therapy with enzalutamide reduced the risk of prostate cancer progression in men on active surveillance but was associated with considerable side effects. We developed a novel polymer-based drug delivery method to provide sustained localized drug administration of anti-androgens selectively to the prostate. In vitro and in vivo mouse and canine studies show that this drug eluting implant delivers sustained high prostate to plasma therapeutic anti-androgen levels for an anticipated range of 2 years while preventing accumulation of anti-androgens in the liver, lungs, heart and brain. We performed a proof of concept study in a canine prostate model implanting an 15mm x 1mm bicalutamide eluting implant into each lobe of the prostate. Bicalutamide levels in the prostate measured near the implant at 6 months were 3250 ± 1622 ng/g, n = 3 compared to 3809 ± 638 ng/g, n = 3 to those achieved at steady-state oral administration. Plasma and other off target levels were over 1000-fold lower in the implant cohort compared to oral administration: Plasma: 5.9 ± 0.2 ng/ml, liver: 11.3 ±4.3 ng/g, and brain: 5.4 ±0.8 ng/g versus plasma: 18170 ± 3820 ng/ml, liver: 35407 ±8510 ng/g, and brain: 8870 ±1797 ng/g. The implants were well tolerated without local toxicity and imaged easily with ultrasound. The design characteristics of the implant facilitates minimally invasive surgical implantation under standard image guidance and withstands the concomitant use of prostate radiation. This novel technology warrants future clinical exploration of prostate specific anti-androgen therapy for (neo)adjuvant therapy or in active surveillance. Tissue Bicalutamide oral (2m)(ng/g) Bicalutamide implant (6m)(ng/g) Plasma 18,170 (3820) 5.9 (0.2) Prostate 3,809 (638) 3,250 (1622) Liver 35,407 (8510) 11.3 (4.3) Cerebrum 8,870 (1797) 5.4 (0.8) Cerebellum 8,737 (1550) 6.2 (1.3) Spleen 7,727 (1288) 4.2 (0.9) Lung 27,013 (2896) 11.3 (4.3) Heart 11,737 (3491) 10.0 (1.9) Kidneys 17,413 (6581) 8.5 (2.0) Citation Format: Pujan Desai, Maithili Rairkar, Nela Pawlowska, Scott Thomas, Pamela N. Munster. Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5261.

Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.

The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophages in vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammation in vivo over 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effects in vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG. STATEMENT OF SIGNIFICANCE: SG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.

Review: emulsion techniques for producing polymer based drug delivery systems

Emulsification method is one of the popular methods for producing materials used inbiosensing, bioimaging and others, especially, drug delivery polymer systems in microsize andnanosize. The concrete techniques related to this method are emulsification, self-emulsification,in a combination with solvent evaporation process, homogenization, or ultranosication. Thestructure of emulsion formulation consists of two phases: an internal phase and an externalphase. Based on the structure and nature of the phases, emulsions can be classified into differenttypes such as two-phase systems (oil in water emulsion (O/W) or water in oil emulsion (W/O))or three-phase systems (water in oil in water triple emulsion (W/O/W) or oil in water in oil tripleemulsion (O/W/O)). The droplet sizes in micro-emulsion systems are often higher than 1 mwhile those in nano-emulsions or mini-emulsions are in the range of 100-500 nm. Some specialnano-emulsion systems can contain droplets with a size of few nanometers. Factors includingsolvents, oil/water phase ratio, droplet oil size, composition ratio, nature of raw materials,emulsifiers, etc. can affect the morphology, properties, and size of the obtained products. Thispaper reviews emulsion techniques which have been applied for producing polymeric drugdelivery systems. The components, properties, characteristics, encapsulation efficiency as wellas drug release rate, water solubility, toxicity and administration efficacy of drug emulsionformulations will be mentioned. Advantages and limitations of emulsion techniques are alsodiscussed.

Exploring the impact of PEGylation on the cell-nanomicelle interactions by AFM-based single-molecule force spectroscopy and force tracing.

PEGylation has been considered the gold standard method for the modification of various drug delivery systems since the last century. However, the impact of PEGylation on the dynamic interaction between drug carriers and cell membranes has not been quantitatively clarified. Herein, the cellular binding and receptor-mediated endocytosis of a model PEGylated polypeptide nanomicelle were systematically investigated at the single-particle level using AFM-based single-molecule force spectroscopy (SMFS) and force tracing. A self-assembled elastin-like polypeptide (ELP) nanomicelle, which is capable of cross-linking, gastrin-releasing peptide (GRP) modification, and PEGylation was prepared. The cross-linked ELP-based nanomicelles exhibited outstanding stability in a broad temperature range of 4-40°C, which facilitate the drug loading, as well as our cell-nanomicelle study at the single particle level. The unbinding force between the cross-linked ELP-based nanomicelles and the GRP receptor (GRPR)-containing cell (PC-3) membranes was quantitatively measured by AFM-SMFS. It is found that the PEGylated GRP-displaying nanomicelles exhibit the highest unbinding force, indicating the enhanced specific binding effect of PEGylation. Furthermore, the receptor-mediated endocytosis of the cross-linked ELP-based nanomicelles was monitored with the help of force tracing based on AFM-SMFS. Our results show that PEGylation decreases the endocytic force, duration, and engulfment depth of the PEGylated GRP-displaying nanomicelles, but increases their endocytic velocity, which results from the elimination of non-specific interactions during endocytosis. These observations demonstrate the diverse and complex roles of PEGylation on the interaction of polypeptide nanomicelles to cell membranes and may shed light on the rational design of organic polymer-based drug delivery systems aiming for active and passive targeting strategies. STATEMENT OF SIGNIFICANCE: A self-assembled elastin-like polypeptide (ELP) nanomicelle, which can be easily cross-linked, gastrin-releasing peptide (GRP) modified, and PEGylated, is designed. The AFM-SMFS experiment shows that PEGylation can enhance specific binding of the nanomicelles to the receptors on cell membranes. The force tracing experiment indicates that PEGylation decreases the endocytic force as well as engulfment depth of the nanomicelles through the elimination of non-specific interactions. PEGylation can benefit the drug delivery systems aiming at active targeting, while might not be an ideal modification for drug carriers designed for passive targeting, whose cellular uptake mainly depends on non-specific interactions.

Structure and dynamics of an active polymer chain inside a nanochannel grafted with polymers.

We use computer simulations to investigate the complex dynamics of a polymer, made of active Brownian particles, inside a channel grafted internally with passive polymer chains. Our simulations reveal that this probe-polymer, if passive, exhibits a compact structure when its interaction is repulsive with the grafted chains as it tends to stay within the hollow space created along the axis of the channel. On increasing the attractive interaction, the passive probe-polymer is pulled towards the grafted polymeric region and adopts an extended structure. By contrast, switching on the activity helps the probe-polymer to escape from the local traps caused by the sticky grafted chains. The interplay between the activity of the probe-polymer and its sticky interaction with the grafted chains results in shrinking, followed by swelling as the activity is increased. To elucidate the dynamics we compute the mean square displacement (MSD) of the center of mass of the probe-polymer, which increases monotonically with activity and displays superdiffusive behavior at an intermediate time and enhanced diffusion at a long time period. In addition, compared with the attractive interaction, the active probe-polymer shows faster dynamics when the interaction is repulsive to the grafted polymers. We believe that our current study will provide insights into the structural changes and dynamics of active polymers in heterogeneous media and will be useful in designing polymer-based drug delivery vehicles.