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Covalent drugs can offer significant advantages over non-covalent drugs in terms of pharmacodynamics (i.e., target-binding properties). However, the development of covalent drugs is sometimes hampered by pharmacokinetic limitations (e.g., low bioavailability, rapid metabolism and toxicity due to off-target binding). Polymeric nanoparticles offer a potential solution to these limitations. Delivering covalent drugs via polymeric nanoparticles provides myriad benefits in terms of drug solubility, permeability, lifetime, selectivity, controlled release and the opportunity for synergistic administration alongside other drugs. In this short review, we examine each of these benefits in turn, illustrated through multiple case studies. [ABSTRACT FROM AUTHOR]

This review discusses the underexploited potential of renewable glycerol and its derivatives for the preparation of active pharmaceutical ingredients, some of which are on the World Health Organization list of essential medicines. The regulatory challenges faced by industries regarding the replacement of petro-based building blocks with renewably sourced ones are described before diving into pharmaceutical ingredients that could potentially incorporate these bio-based atoms. The active pharmaceutical ingredients (APIs) are sorted by their therapeutical potential, including entities treating cardiovascular diseases, musculoskeletal drugs and compounds endowed with anti-infective properties. Finally, polymeric drugs and more eclectic substrates such as dietary supplements, radiosensitizers or chemotherapeutical agents are considered in the last two sub-sections. The broad spectrum of presented substrates relying on glycerol or potentially glycerol-derived reagents in their synthetic pathway emphasizes the potential contribution of bio-based substrates in already developed industrial processes. The examples in this review hint toward a future chemical development in which APIs may be constructed with increasing percentages of bio-sourced atoms. [ABSTRACT FROM AUTHOR]

In the production of polymeric drug delivery devices, dissolution profile and mechanical properties of the drug loaded polymeric matrix are considered important Critical Quality Attributes (CQA) for quality assurance. However, currently the industry relies on offline testing methods which are destructive, slow, labour intensive, and costly. In this work, a real-time method for predicting these CQAs in a Hot Melt Extrusion (HME) process is explored using in-line NIR and temperature sensors together with Machine Learning (ML) algorithms. The mechanical and drug dissolution properties were found to vary significantly with changes in processing conditions, highlighting that real-time methods to accurately predict product properties are highly desirable for process monitoring and optimisation. Nonlinear ML methods including Random Forest (RF), K-Nearest Neighbours (KNN) and Recursive Feature Elimination with RF (RFE-RF) outperformed commonly used linear machine learning methods. For the prediction of tensile strength RFE-RF and KNN achieved R2 values 98% and 99%, respectively. For the prediction of drug dissolution, two time points were considered with drug release at t = 6 h as a measure of the extent of burst release, and t = 96 h as a measure of sustained release. KNN and RFE-RF achieved R2 values of 97% and 96%, respectively in predicting the drug release at t = 96 h. This work for the first time reports the prediction of drug dissolution and mechanical properties of drug loaded polymer product from in-line data collected during the HME process. [ABSTRACT FROM AUTHOR]

The presented experiments aimed to synthesize multi-targeted polymeric antibody-microparticles for the treatment of CD19+/CD20+ cancers. It is hypothesized that (1) targeting multiple tumor specific antigen (TSA) improves drug delivery by increasing binding in patients with low TSA expression and (2) polymeric drug encapsulation enables controlled drug release. Protein-bound paclitaxel was successfully entrapped in biotin-avidin-antibody coated poly(lactic-co-glycolic acid) (PLGA). Targeting layers and antibody attachment did not negatively impacted drug release in vitro. Cell viability was reduced after administration in target cell lines. The presented technology forms a foundation for further investigation of multi-targeted polymeric antibody-microparticle conjugates capable of optimizing cancer treatment. [ABSTRACT FROM AUTHOR]

Intratumor microbes have attracted great attention in cancer research due to its influence on the tumorigenesis, progression and metastasis of cancer. However, the therapeutic strategies targeting intratumoral microbes are still in their infancy. Specific microorganisms, such as Fusobacterium nucleatum (F. nucleatum), are abundant in various cancer and always result in the CRC progression and chemotherapy resistance. Here, a combined anticancer and antibacterial therapeutic strategy is proposed to deliver antitumor drug to the tumors containing intratumor microbiota by the antibacerial polymeric drug carriers. We construct oral tellurium-containing drug carriers using a complex of tellurium-containing polycarbonate with cisplatin (PTE@CDDP). The results show that the particle size of the prepared nanoparticles could be maintained at about 105 nm in the digestive system environment, which is in line with the optimal particle size of oral nanomedicine. In vitro mechanism study indicates that the tellurium-containing polymers are highly effective in killing F.nucleatum through a membrane disruption mechanism. The pharmacokinetic experiments confirmed that PTE@CDDP has the potential function of enhancing the oral bioavailability of cisplatin. Both in vitro and in vivo studies show that PTE@CDDP could inhibit intratumor F.nucleatum and lead to a reduction in cell proliferation and inflammation in the tumor site. Together, the study identifies that the CDDP-loaded tellurium-containing nanoparticles have great potential for treating the F.nucleatum -promoted colorectal cancer (CRC) by combining intratumor microbiota modulation and chemotherapy. The synergistic therapeutic strategy provide new insight into treating various cancers combined with bacterial infection. The synthesized antibacterial polymer was first employed to remodel the intratumor microbes in tumor microenvironment (TME). Moreover, it was the first report of tellurium-containing polymers against F.nucleatum and employed for treatment of the CRC. A convenient oral dosage form of cisplatin (CDDP)-loaded tellurium-containing nanoparticles (PTE@CDDP) was adopted here, and the synergistic antibacterial/chemotherapy effect occurred. The PTE@CDDP could quickly and completely eliminate F.nucleatum in a safe dose. In the CRC model, PTE@CDDP effectively reversed the inflammation level and even restored the intestinal barrier damaged by F.nucleatum. The ultrasensitive ROS-responsiveness of PTE@CDDP triggered the fast oxidation and efficient drug release of CDDP and thus a highly efficient apoptosis of the tumors. Therefore, the tellurium-containing polymers are expected to serve as novel antibacterial agents in vivo and have great potential in the F.nucleatum -associated cancers. The achievements provided new insight into treating CRC and other cancers combined with bacterial infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Sequential NanoPrecipitation (SNaP) is a nascent controlled precipitation process for the tunable formation of polymeric particles for drug delivery and bioimaging. While SNaP utilizes the same self‐assembly principles as one‐step Flash NanoPrecipitation, SNaP is a two‐step assembly process in which the particle core formation is initiated during a first mixing step followed by particle stabilization in a second mixing step. Current SNaP experimental set‐ups use commercial millifluidic mixers connected in series, which have several limitations, including the inability to access short inter‐mixer delay times (Td). A robust, 3D‐printed, modular mixer design that enables access to short Td's (〈 25 ms) not previously accessible is reported. For the first time, it is demonstrated that decoupling the assembly steps improves control over particle size, expanding the attainable size range to include both nanoparticles and microparticles. It is empirically proven that inter‐mixer Td is a key parameter for particle size control and that particle size scales with Td in agreement with Smoluchowski's model of diffusion‐limited growth. The formation of particles ranging in size from 160 nm to 1.2 µm is shown. Finally, the applicability of the new mixers is established by encapsulating fluorophores and therapeutics into particles for the first time via SNaP. [ABSTRACT FROM AUTHOR]

This study explores the impact of varying temperatures on the release behavior of Triptorelin Acetate (TA) from a PLGA-based in-situ forming implant (ISFI) and polymer degradation. Formulations were prepared using the in situ forming method in an acetate buffer (pH = 6.8) and then exposed to temperatures of 4 to 60 °C. The drug release and polymeric depot behavior were evaluated using HPLC, SEM, GPC, Rheometer, and pH measurements. A modified Gallagher-Corrigan Model-based mathematical model was applied to fit the in-vitro data, and the activation energy for peptide release in diffusional and erosional phases was calculated using the Arrhenius equation. The results revealed that matrices formed at 37, 45, and 53 °C exhibited a highly porous structure, resulting from rapid phase inversion and surface pore closing. This led to a reduction in TA burst release, observed as 38%, 27%, and 15% at 37 °C, 45 °C, and 53 °C respectively. Conversely, matrices at 4 and 25 °C demonstrated a faster initial release, followed by the formation of dense structures. The accelerated drug release profiles at 45 and 53 °C showed a shortened ultimate drug release duration and a good correlation with the real-time results at 37 °C. Due to the discernible PLGA matrices degradation at different temperatures, biphasic and tri-phasic release patterns were observed. The experimental release results aligned well with the proposed mathematical model, and the drug release kinetic parameters were estimated. Thus, in in-vitro studies, the release medium temperature plays a significant role in the drug-release behavior of ISFIs. [ABSTRACT FROM AUTHOR]

Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property. [ABSTRACT FROM AUTHOR]

Studies in which polymeric nanoparticles are used in drug delivery have been one of the subjects of interest in recent years. In this study, histidine-containing polymeric nanoparticles [poly(2-hydroxyethyl methacrylate-co-N-methacryloylamido histidine methyl ester)] were synthesized by surfactant free emulsion polymerization method. Ciprofloxacin was loaded onto the HPCNs surface [CIP-HCPNs]. In the characterization of CIP-HCPNs, scanning electron microscopy, Fourier-infrared analysis, surface area calculations and zeta potential analysis were used. FT-IR data of histidine-free polymeric nanoparticles [HFPNs] and HCPNs demonstrated the successful addition of Histidine to polymeric nanoparticles. SEM images showed that CIP-HCPNs had a size of 131.2 nm with a spherical shape. As a result of Zeta potential studies, the polydispersity index (PDI) of CIP-HCPNs was found to be 0.11, indicating that CIP-HCPNs have a narrowly spaced size distribution. CIP release from CIP-HCNPs showed slow-release properties. At pH 7.4, cumulative CIP release from CIP-HCPNs was 96% (283.35 mg/g) within 6 h, with full drug release achieved at 24 h. It was stated that the drug release kinetic data obtained from CIP release experiments fit the Hixson-Crowell model, and in this model, CIP release from CIP-HCPNs occurred as the square root of the time dependent process based on Fickian diffusion. As a result, CIP-HCNPs developed in the current study, it can be said that it is suitable for drug release. [ABSTRACT FROM AUTHOR]

[Display omitted] Implantation of a biomaterial entails a form of injury where the integration of the implant into the host tissue greatly depends on the proper healing of the wound. Wound healing, itself, consists of a number of physiological processes, each occurring within a characteristic time window. A composite, multilayered polymeric drug delivery carrier for adhesion to the wound site and its supply with molecules released at precise time windows at which the stages in the healing process that they target occur is conceptualized here. We also present a simplified version of one such multilayered composite fabricated by a combination of solvent casting and dip coating, comprising the base poly(ε-caprolactone) layer reinforced with hydroxyapatite nanoparticles, poly(glutamic acid) mesolayer and poly- l -lysine surface layer, each loaded with specific small molecules and released at moderately distinct timescales, partially matching the chronology of wound healing. To that end, the base layer proved suitable for the delivery of an anti-inflammatory molecule or an angiogenic agent, the mesolayer appeared appropriate for the delivery of an epithelialization promoter or a granulation factor, and the adhesive surface layer interfacing directly with the site of injury showed promise as a carrier of a vasodilator. The drug release mechanisms were diffusion-driven, suggesting that the drug/carrier interaction is a key determinant of the release kinetics, as important as the nature of the polymer and its hydrolytic degradation rate in the aqueous medium. Morphological and phase composition analyses were performed, along with the cell compatibility ones, demonstrating solid adhesion and proliferation of both transformed and primary fibroblasts on both surfaces of the composite films. The design of the multilayered composite drug delivery carriers presented here is prospective, but requires further upgrades to achieve the ideal of a perfect timing of the sequential drug release kinetics and a perfect resonance with the physiological processes defining the chronology of wound healing. [ABSTRACT FROM AUTHOR]

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review. [ABSTRACT FROM AUTHOR]

Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague–Dawley rats. Nanoparticle delivery significantly reduced the IC50 of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC50 (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 μg/mL) was substantially higher than in plasma (0.7 ± 0.05 μg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure. [ABSTRACT FROM AUTHOR]

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011–0.063 mg/mL to 0.027–0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy. [ABSTRACT FROM AUTHOR]

Gambogic acid (GA) and combretastatin A-4 (CA-4) were used as antitumor drugs to prepare three-armed polymers (TPs) by reversible addition–fragmentation chain-transfer polymerization, atom-transfer radical polymerization and click polymerization. Gel permeation chromatography characterization showed that the molecular weights of glucose cyanine 7.5 (Cy7.5), carboxyl-terminated chain transfer agent (C7A) and polyethylene glycol (PEG) in CTA-PEG5k-Lys-AzMA-Cy7.5-C7A TP were 5000. The grain size of GA and CA-4 embedded in 10 mg TP and linear polymer (LP) is 3.2 mg. The toxicity of CA-4 is low, while the toxicity of GA is high. For the LP and TP, a higher apoptosis rate is produced under laser irradiation. The polymers are aggregated at the tumor site, which indicates that the polymer system has a better in vivo distribution effect, and the aggregation effect of the TP is better than that of the LP. The TP prepared by this research has good antitumor effect and biological effect and can be popularized and applied in the targeted treatment of tumor diseases. [ABSTRACT FROM AUTHOR]

The article discusses the application of polymeric micelles for drug and gene delivery. Polymeric micelles are colloidal particles composed of a hydrophobic core surrounded by a hydrophilic shell, formed by the aggregation of amphiphilic block copolymers in an aqueous solution. These micelles can effectively solubilize hydrophobic drugs, provide controlled and targeted drug release, and protect the drug from biological invasion. The article presents recent research on the use of polymeric micelles for delivering anticancer therapeutics, antibiotics, immunosuppressants, and nucleic acids. It also highlights the ability of polymeric micelles to co-deliver multiple therapeutics and reviews the advancements in polymeric micelle design for the delivery of biomolecules. [Extracted from the article]

Polymeric micelles (PM) are amphiphilic block copolymers that can form nanoscopic core/shell structures, making them highly effective for drug delivery systems (DDS). Multi‐armed starshaped poly(ethylene glycol) (PEG) polymers, a promising type of PM, provide a regulated release of drugs and can be integrated with numerous endpoints to create multifunctional drug delivery systems capable of transporting a large number of drugs. Star‐PEG polymers can also be cross‐linked to create three dimensional hydrogels with variable functionalities and sizes, increasing blood flow and reducing unanticipated drug release. In this review, we present state‐of‐the‐art computational tools for analyzing drug pharmacokinetic profiles and identifying molecular interactions critical for successful drug encapsulation in star‐PEG PM. By taking into account the features described, academic and industrial researchers can identify novel interrelationships in PM and maximize their capabilities as DDSs for systemic administration, ultimately enhancing the medicinal qualities of drug delivery. [ABSTRACT FROM AUTHOR]

Drug-eluting stents (DES) are the best choice of the current era to open the occluded arteries. Its success depends upon the concentration of the drug and overall release kinetics, which in turn is subjected to the polymeric drug carrier and mechanism of drug release at the target area. Each generation of DES possess different characteristics based on different aspects i.e., polymer type, coating layer thickness, and drug concentration have been discussed. This review paper discusses all the polymers utilized in DES systems and their release profiles when combined with multiple drugs for the treatment of coronary heart disease. Drug-coated metal stents are used to support and improve the quality of life of patients with cardiovascular diseases. This review describes the properties of drug-eluting stent from different generations and challenges they offered. Nature of polymeric drug carriers affects the inflammation, lesion healing, rate of restenosis, and thrombosis. Ongoing research in DES technology aims to avoid the challenges offered by non-erodible polymeric drug carriers. Third-generation DES utilizes PLA-based polymers which are biocompatible, flexible, and erodible. Bioresorbable DES is future of DES technology; however, it is still in primitive stages and overcoming the issues of mechanical strength and corrosion. [ABSTRACT FROM AUTHOR]

The significance of 3D printing has risen exponentially in biomedical and pharmaceutical applications. Its potential in the field of fabricating drug delivery systems, by virtue of processing biocompatible polymers, has been very lucrative. This work aims to tap the interstitial drug delivery kinetics that are often inaccessible through machine‐specific infill patterns in additive manufactured tablets fabricated using PVA biopolymer as an excipient. In this regard, a myo‐inositol containing tablet has been printed using Fused Deposition Modeling preceded by Hot Melt Extrusion drug loading route. Two machine‐specific infill patterns were taken, namely straight and grid. Later, these two distinct patterns were juxtaposed to obtain novel hybrid infill patterns in the tablets. Then, these tablets and their filament were subjected to various thermal, mechanical, imaging and pharmaceutical characterization tests to assess the feasibility of the research attempt. Finally, dissolution tests were conducted to evaluate their dissolution behavior over a time period. The characterization tests proved the scientific viability of this attempt along with amorphous existence of drug in the polymeric filament. The dissolution results showed favorable drug release by achieving interstitial dissolution timings with surface area/volume (SA/V) ratio being found to be the principal factor. [ABSTRACT FROM AUTHOR]

Breast cancer comprises approximately 20% of all malignant neoplasm cases globally. Due to the limitations associated with conventional therapeutic approaches, extensive investigations have been undertaken to develop novel treatments that exhibit enhanced specificity and minimized adverse effects. Consequently, the application of polymeric nanoformulations for targeted drug delivery has gained significant attention within the biomedical field. Therefore, the primary objective of this study was to explore the inherent advantages and efficacy of employing polymeric nanoformulations for drug delivery in breast cancer treatment, as compared to traditional therapies. A comprehensive literature search was conducted across prominent databases including PubMed/MEDLINE, Embase, and Scopus, utilizing specific search strings. This meticulous approach yielded a total of 12 relevant articles for in-depth analysis and discussion. The findings from the selected studies underscore the effectiveness of employing polymeric nanoparticles as a drug delivery strategy, showcasing noteworthy improvements in cellular uptake and sustained intracellular retention of encapsulated therapeutic agents. Additionally, these nanoformulations exhibited superior efficacy, safety, and drug delivery capabilities. The utilization of polymeric nanoparticles in drug delivery has demonstrated a substantial enhancement in treatment efficacy, with the ability to achieve higher concentrations of active ingredients within tumor tissues, augment cellular uptake and drug concentrations, and sustain intracellular retention. Consequently, this innovative approach prolongs drug release in lower quantities, ultimately contributing to improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5–50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5–7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications. [ABSTRACT FROM AUTHOR]

Copper nanoparticles have been utilized in a variety of therapeutic applications because of their inexpensive manufacturing and unique characteristics. In the current study, novel nanocomposites are developed to carry bioactive agents in a controlled manner. Copper nanoparticles (Cu‐NPs) were synthesized from copper sulfate using a leaf extract of Phyllanthus virgatus as a reducing agent. The obtained Cu‐NPs are loaded into the polymeric matrix of sodium alginate and locust bean gum to generate microbeads. The developed microbeads were characterized by Fourier‐transform infrared (FTIR), X‐ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and scanning electron microscope (SEM). Swelling and in vitro release studies were performed at pH 2.0 and 7.4 at 37 °C. Metronidazole (MTD) was used as a model agent, and the antibacterial activity of microbeads was tested against Streptococcus mutans, Klebsiella pneumoniae, and Bacillus subtilis. The release kinetics and MTD release pattern were analyzed by employing the MTD release data into Korsmeyer‐Peppas equation and other kinetic models. [ABSTRACT FROM AUTHOR]

Although essential nanosystems such as nanoparticles and nanocarriers are desirable options for transporting various drug molecules into the biological environment, they rapidly remove from the circulatory system due to their interaction with multiple in vivo barriers, especially the immune barrier, which will result in their short-term effects. In order to improve their effectiveness and durability in the circulatory system, the polymer coatings can use to cover the surface of nanoparticles and nanocarriers to conceal them from the immune system. Due to their different properties (like charge, elasticity, and hydrophilicity/hydrophobicity), these coatings can improve drug delivery nanosystem durability and therapeutic applications. The mentioned coatings have different types and are divided into various categories, such as synthetic polymers, polysaccharides, and zwitterionic polymers. Each of these polymers has unique properties based on its category, origin, and chemical structure that make them suitable for producing stealth drug delivery nanocarriers. In this review article, we have tried to explain the importance of these diverse polymer coatings in determining the fate of drug nanocarriers and then introduced the different types of these coatings and, finally, described various methods that directly and indirectly analyze the nanocoatings to determine the stability of nanoparticles in the body. Graphical Abstract [ABSTRACT FROM AUTHOR]

In this study, novel materials have been obtained via a dual covalent and ionic crosslinking strategies, leading to the formation of a fully interpenetrated polymeric network with remarkable mechanical performances as drug delivery platforms for dermal patches. The polymeric network was obtained by the free-radical photopolymerization of N-vinylpyrrolidone using tri(ethylene glycol) divinyl ether as crosslinker in the presence of sodium alginate (1%, weight%). The ionic crosslinking was achieved by the addition of Zn2+, ions which were coordinated by the alginate chains. Bentonite nanoclay was incorporated in hydrogel formulations to capitalize on its mechanical reinforcement and adsorptive capacity. TiO2 and ZnO nanoparticles were also included in two of the samples to evaluate their influence on the morphology, mechanical properties and/or the antimicrobial activity of the hydrogels. The double-crosslinked nanocomposite hydrogels presented a good tensile resistance (1.5 MPa at 70% strain) and compression resistance (12.5 MPa at a strain of 70%). Nafcillin was loaded into nanocomposite hydrogel films with a loading efficiency of up to 30%. The drug release characteristics were evaluated, and the profile was fitted by mathematical models that describe the physical processes taking place during the drug transfer from the polymer to a PBS (phosphate-buffered saline) solution. Depending on the design of the polymeric network and the nanofillers included, it was demonstrated that the nafcillin loaded into the nanocomposite hydrogel films ensured a high to moderate activity against S. aureus and S. pyogenes and no activity against E. coli. Furthermore, it was demonstrated that the presence of zinc ions in these polymeric matrices can be correlated with the inactivation of E. coli. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the potential of low‐generation polyamidoamine (PAMAM) dendrimers as drug nanocarriers for 5‐fluorouracil (5‐FU), an anticancer drug, and to determine the type of dendrimer generation (half or full) with the highest drug load capacity and slowest release rate. For this, PAMAM dendrimers (up to 2.0 generation) were synthesized and characterized by means of spectroscopic techniques and thermal analysis. Then, 5‐FU was successfully incorporated into dendrimers, and the resulting complexes were characterized in terms of their, elemental composition, spectroscopy, thermal behavior, and loading efficacy. In addition, in vitro release studies of 5‐fluorouracil from complexes were conducted using phosphate‐buffered saline; and the 5‐FU release kinetics was also modeled. The successful synthesis of PAMAM dendrimers was confirmed by Fourier transform infrared spectroscopy (FTIR), 1H‐NMR, UV–vis, dynamic light scattering and thermogravimetric analysis (TGA) analysis. Energy‐dispersive X‐ray spectroscopy (EDX), FTIR, UV–vis and TGA results confirmed the complexation phenomena among PAMAM dendrimers and 5‐FU drug. It was found that the encapsulation efficiency and drug release rate are a function of generation type, and that the full‐generation dendrimers showed the best results. The Korsmeyer‐Peppas model best described the kinetics of drug release for all complexes. These results confirm that the proposed low‐generation dendrimers are suitable polymeric nanocarriers for drug delivery applications. [ABSTRACT FROM AUTHOR]

Here, super-macroporous cryogel from a natural polysaccharide, pullulan was synthesized using a cryo-crosslinking technique with divinyl sulfone (DVS) as a crosslinker. The hydrolytic degradation of the pullulan cryogel in various simulated body fluids (pH 1.0, 7.4, and 9.0 buffer solutions) was evaluated. It was observed that the pullulan cryogel degradation was much faster in the pH 9 buffer solution than the pH 1.0 and 7.4 buffer solutions in the same time period. The weight loss of the pullulan cryogel at pH 9.0 within 28 days was determined as 31% ± 2%. To demonstrate the controllable drug delivery potential of pullulan cryogels via degradation, an antibiotic, ciprofloxacin, was loaded into pullulan cryogels (pullulan-cipro), and the loading amount of drug was calculated as 105.40 ± 2.6 µg/mg. The release of ciprofloxacin from the pullulan-cipro cryogel was investigated in vitro at 37.5 °C in physiological conditions (pH 7.4). The amount of drug released within 24 h was determined as 39.26 ± 3.78 µg/mg, which is equal to 41.38% ± 3.58% of the loaded drug. Only 0.1 mg of pullulan-cipro cryogel was found to inhibit half of the growing Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) colonies for 10 min and totally eradicated within 2 h by the release of the loaded antibiotic. No significant toxicity was determined on L929 fibroblast cells for 0.1 mg drug-loaded pullulan cryogel. In contrast, even 1 mg of drug-loaded pullulan cryogel revealed slight toxicity (e.g., 66% ± 9% cell viability) because of the high concentration of released drug. [ABSTRACT FROM AUTHOR]

The development of biocompatible and efficient polymeric micelles for drug delivery has been drawing great attention. Herein, amphiphilic molecules (PMPC) were synthesized with zwitterionic linear polyethyleneimine (PEI) as the hydrophilic segment and mercapto-paclitaxel as the hydrophobic segment. The chemotherapeutic doxorubicin (DOX) was encapsulated in the PMPC micelles formed through self-assembly to prepare DOX-loaded micelles (PMPC–DOX micelles). The results showed that the prepared PMPC–DOX micelles exhibited good stability in protein solution. The release rate of DOX reached 48.12% within 36 h at pH 5.5. More importantly, the tumor targeting ability and the antitumor effect of PMPC–DOX micelles were better than those of free DOX, and the tumor inhibition rate of mice was 89.7% after 14 days of treatment. The as-prepared PEI-based drug-loaded micelles provide a new approach for the design of nanodrug delivery systems. [ABSTRACT FROM AUTHOR]

Continuous drug delivery modification is the scientific approach and is a basic need for the efficient therapeutic efficacy of active drug molecules. Polymer-drug conjugates have long been a hallmark of the drug delivery sector, with various conjugates on the market or in clinical trials. Improved drug solubilization, extended blood circulation, decreased immunogenicity, controlled release behavior, and increased safety are the advantages of conjugating drugs to the polymeric carrier like polyethylene glycol (PEG). Polymer therapies have evolved over the last decade, resulting in polymer-drug conjugates with diverse topologies and chemical properties. Traditional nondegradable polymeric carriers like PEG and hydroxy propyl methacrylate have been clinically employed to fabricate polymer-drug conjugates. Still, functionalized polymer-drug conjugates are increasingly being used to increase localized drug delivery and ease of removal. Researchers have developed multifunctional carriers that can "see and treat" patients using medicinal and diagnostic chemicals. This review focused on the various conjugation approaches for attaching the doxorubicin to different polymers to achieve enhanced therapeutic efficacy, that is, increased bioavailability and reduced adverse effects. [ABSTRACT FROM AUTHOR]

(1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltrative cancerous cells, with minimum toxic effects toward normal tissue. (2) Methods: MIP reservoirs were synthesized by precipitation polymerization using acrylamide, trifluoromethacrylic acid, methacrylic acid, and styrene as monomers. Drug release profiles were evaluated by real-time and accelerated release studies in phosphate-buffered solution as a release medium. The cytotoxicity of polymers and free monomers was evaluated in vitro on GBM C6 cells using the Alamar Blue assay, optical microscopy, and CCK8 cell viability assay. (3) Results: Among the four synthesized MIPs, trifluoromethacrylic acid-based polymer (MIP 2) was superior in terms of loading capacity (69.9 μg RUX/mg MIP), drug release, and efficacy on GBM cells. Accelerated drug release studies showed that, after 96 h, MIP 2 released 42% of the loaded drug at pH = 7.4, with its kinetics fitted to the Korsmeyer–Peppas model. The cell viability assay proved that all studied imprinted polymers provided high efficacy on GBM cells. (4) Conclusions: Four different drug-loaded MIPs were developed and characterized within this study, with the purpose of obtaining a drug delivery system (DDS) embedded in a fibrin-based hydrogel for the local, post-surgical administration of RUX in GBM in animal models. MIP 2 emerged as superior to the others, making it more suitable and promising for further in vivo testing. [ABSTRACT FROM AUTHOR]

Proteins-derived polymeric micelles have gained attention and revolutionized the biomedical field. Proteins are considered a favorable choice for developing micelles because of their biocompatibility, harmlessness, greater blood circulation and solubilization of poorly soluble drugs. They exhibit great potential in drug delivery systems as capable of controlled loading, distribution and function of loaded agents to the targeted sites within the body. Protein micelles successfully cross biological barriers and can be incorporated into various formulation designs employed in biomedical applications. This review emphasizes the recent advances of protein-based polymeric micelles for drug delivery to targeted sites of various diseases. Most studied protein-based micelles such as soy, gelatin, casein and collagen are discussed in detail, and their applications are highlighted. Finally, the future perspectives and forthcoming challenges for protein-based polymeric micelles have been reviewed with anticipated further advances. [ABSTRACT FROM AUTHOR]

The alliance between 3D printing and nanomaterials brings versatile properties to pharmaceuticals, but few studies have explored this approach in the development of skin delivery formulations. In this study, clobetasol propionate (CP) was loaded (about 25% w/w) in mesoporous silica nanomaterial (MSN) to formulate novel bioadhesive and hydrophilic skin delivery films composed of pectin (5% w/v) and carboxymethylcellulose (5% w/v) by 3D printing. As a hydrophobic model drug, CP was encapsulated in MSN at a 3:1 (w/w) ratio, resulting in a decrease of CP crystallinity and an increase of its dissolution efficiency after 72 h (65.70 ± 6.52%) as compared to CP dispersion (40.79 ± 4.75%), explained by its partial change to an amorphous form. The CP-loaded MSN was incorporated in an innovative hydrophilic 3D-printable ink composed of carboxymethylcellulose and pectin (1:1, w/w), which showed high tensile strength (3.613 ± 0.38 N, a homogenous drug dose (0.48 ± 0.032 mg/g per film) and complete CP release after 10 h. Moreover, the presence of pectin in the ink increased the skin adhesion of the films (work of adhesion of 782 ± 105 mN·mm). Therefore, the alliance between MSN and the novel printable ink composed of carboxymethylcellulose and pectin represents a new platform for the production of 3D-printed bioadhesive films, opening a new era in the development of skin delivery systems. [ABSTRACT FROM AUTHOR]

Introduction: Class II drugs represent a high percentage of the molecules in the biomedical research phase. This group has attracted research in recent years, since its low aqueous solubility conditions its absorption in vivo, which poses a challenge for pharmaceutical technology. Solid dispersion design (SD) is a technique that has been successful and is based on the dispersion of the drug in a polymeric carrier, promoting the amorphous state of the former. One of the methods of obtaining SD is melting, which can be carried out in sophisticated equipment, but high shear mixers (HSM) are also an alternative to obtain granules by melting. Aim: The objective of this work is to review if melt granulation processes have been reported using HSM for the manufacture of SD and to analyze the strengths, weaknesses, opportunities and threats of this equipment in said process. Method: In a documentary review methodology, 90 publications from the PubMed, ScienceDirect and Google Scholar databases from the last 20 years were pre-selected, of which eight describe the use of the fusion granulation method in HSM. Results: As results, it was seen that 100% of these cases reported higher solubility and dissolution speed than the pure drug. It is concluded that local companies that have HSM have the potential to launch successful SD manufacturing processes in HSM, with the advantage of not making an additional investment. [ABSTRACT FROM AUTHOR]

Cholic acid based biodegradable reverse polymeric micelles have been widely utilized as preclinically suitable drug delivery system for poorly water-soluble drugs. In this report, we developed N -acetylcysteine functionalized cholic acid based triarmed poly (D l -lactide) (ACyCA-triarmed (DLL) n as reversed polymeric micelles for drug delivery studies. ACyCA was synthesized via thiol-yne click reaction and subsequently used as an initiator for the synthesis of ACyCA-triarmed (DLL) n through ring opening polymerization (ROP) using Sn (Oct) 2 as a catalyst. The synthesized ACyCA-triarmed (DLL) n was characterized using GPC, FT-IR, 1H NMR, 13C NMR, spectrofluorometer, HR-TEM, DSC, TGA, XRD, DLS, and zeta potential techniques. The reverse critical micellar concentration of the polymer was determined to be 1.99 mg/mL using a spectrofluorometer. The synthesized reverse micelles (RMs) were utilized as a reducing and capping agent for the preparation of AuNPs under sunlight exposure. The formed AuNPs exhibited spherical in shape with an average size of ∼ 23.4 nm and D h was found to be 86.8 ± 1.3 nm as evidenced by the TEM and DLS analysis. Furthermore, the antimicrobial activity, hemolytic activity, anti-oxidant activity, and in-vitro drug release studies were examined for the RMs-AuNPs and compared with RMs. The hydrophobic nature of RMs and RMs-AuNPs had better haemocompatibility at above the reversed CMC. The antioxidant activity RMs-AuNPs showed better inhibitory effect in a dose-dependent manner as compared to RMs. The RMs-AuNPs formulation act as reservoir for solubilization of hydrophobic doxorubicin (Dox.HCl) drugs and can be used as therapeutic platform for slow and sustained release of drugs in biological medium. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Long-acting parenteral drug products are a popular choice for therapeutic areas requiring long term treatment. These products range from dispersed systems such as drug suspensions and polymeric microspheres to in situ forming polymeric implants. The lack of reliable drug release testing methods for these drug products not only impedes the development of new drug products but also affects generic drug development. Current release methods suffer from a range of problems such as high variability, poor reproducibility, poor discriminatory ability, lack of depot-like structure formation (that could mimic the in vivo situation). Moreover, shorter duration (less than a week) of release renders them unsuitable for in vitro-in vivo correlations (IVIVCs). To overcome these issues, novel adapters were developed for both USP-type-II & IV apparatus. These adapters were validated and assessed using the long-acting injectable (LAI) suspension drug product Depo Provera 150® as well as its Q1/Q2 equivalents. For USP-type-IV apparatus, two open adapter designs (conical and ellipsoidal shaped cavity with volume capacities of 50 µl and 1 ml, respectively) were developed. A closed conical adapter design with a volume capacity of 0.05 ml was developed for USP apparatus type-II. All three novel adapter designs effectively retained the suspensions, achieved release durations of 3–6 weeks with good reproducibility, minimal variability (RSD≤5%) and had good discriminatory ability. Based on this, the adapter-based dissolution methods were deemed suitable for IVIVC development of long-acting injectables. A successful Level A IVIVC was developed for Depo SubQ Provera 104® and its Q1Q2 equivalents using USP apparatus type IV with a conical adapter design. The closed adapter design for apparatus type-II was also investigated for suitability with risperidone in situ forming implants. The adapter was able to securely retain and maintain the shape of the in situ forming implants and resulted in release profiles of up to one month with good discriminatory ability and low standard error (RSD≤5%). These novel adapters hold promise of wide use for in vitro release testing of different long-acting parenteral drug products. [ABSTRACT FROM AUTHOR]

[Display omitted] • The novel PDEAAm- g -HbPG graft copolymers possess reversible thermoresponsive behavior in water and PBS, affected by the composition and the concentration of the macromolecules. • Highly efficient encapsulation of curcumin by the graft copolymers takes place even at room temperature, and the drug loading content increases with temperature up to 25%. • The PDEAAm- g -HbPG graft copolymers exhibit excellent colloidal stability and biocompatibility, and by using these graft copolymers as drug carriers, the antiproliferative effect of curcumin is advantageously enhanced. Due to solubilization, encapsulation, stability and delivery difficulties of various drugs and drug candidates, investigating polymeric nanoparticles for drug delivery formulations is an extremely vital and challenging task. The ideal polymers should have biocompatibility, controlled drug uptake/release properties and colloidal stability over a wide temperature range. In this study, we propose poly(N , N -diethylacrylamide)- g -(hyperbranched polyglycerol) (PDEAAm- g -HbPG) thermoresponsive graft copolymers as candidates for drug formulations satisfying all the above-mentioned requirements. The PDEAAm- g -HbPG copolymers were synthesized by grafting amino-monofunctional HbPG onto PDEAAm chains containing pendant succinimide active ester groups. It has been found that the PDEAAm- g -HbPG graft copolymers are non-toxic to human monocytic cells, and do not cause haemolysis of human red blood cells. Furthermore, these grafts possess temperature-dependent reversible aggregation-disaggregation, i.e. thermoresponsive transitions, in water and PBS. The specific nanoassembling architecture of the copolymers resulted in enhanced encapsulation of curcumin with high drug loading content exceeding 25 % at 37 °C. The hydrophilic HbPG side chains provide high colloidal stability for the formulated drug dispersions from room temperature up to 45 °C as well as sustained release of curcumin. Formulating curcumin with these novel graft copolymers significantly enhanced its anticancer activity against HT-29 colorectal adenocarcinoma cells and the cell internalization of the drug. These properties of PDEAAm- g -HbPG copolymers make them superior compared to other hydrophilically modified polymer carriers indicating their great potential as advanced drug delivery systems. [ABSTRACT FROM AUTHOR]

Muco-adhesive drug delivery systems continue to be one of the most studied for controlled pharmacokinetics and pharmacodynamics. Briefly, muco-adhesive polymers, can be described as bio-polymers that adhere to the mucosal (mucus) surface layer, for an extended residency period of time at the site of application, by the help of interfacial forces resulting in improved drug delivery. When compared to traditional drug delivery systems, muco-adhesive carriers have the potential to enhance therapeutic performance and efficacy, locally and systematically, in oral, rectal, vaginal, amongst other routes. Yet, the achieving successful muco-adhesion in a novel polymeric drug delivery solution is a complex process involving key physico-chemico-mechanical parameters such as adsorption, wettability, polymer chain length, inter-penetration and cross-linking, to list a few. Hence, and in light of accruing progress, evidence and interest, during the last decade, this review aims to provide the reader with an overview of the theories, principles, properties, and underlying mechanisms of muco-adhesive polymers for pharmaceutics; from basics to design to characterization to optimization to evaluation to market. A special focus is devoted to recent advances incorporating bio-inspired polymers for designing controlled muco-adhesive drug delivery systems. [ABSTRACT FROM AUTHOR]

Researchers are increasingly thinking smaller to solve some of the biggest challenges in nanomedicine: the control of drug encapsulation. Although recent years have witnessed a significant increase in the development and characterization of polymeric drug nanocarriers, several key features are still to be addressed: Where is the drug located within each nanoparticle (NP)? How much drug does each NP contain? Is the drug loading homogeneous on an individual NP basis? To answer these questions, individual NP characterization was achieved here by using atomic force microscopy-infrared spectroscopy (AFM-IR). A label-free quantification methodology was proposed to estimate with a nanoscale resolution the drug loadings of individual poly(lactic acid) (PLA) NPs loaded with an anticancer drug. First, a drug loading calibration curve was established using conventional IR microspectroscopy employing PLA/drug homogeneous films of well-known compositions. Then, single NPs were investigated by AFM-IR acquiring both IR mappings of PLA and drug as well as local IR spectra. Besides, drug location within single NPs was unravelled. The measured drug loadings were drastically different (0 to 21 wt%) from one NP to another, emphasizing the particular interest of this methodology in providing a simple quantification method for the quality control of nanomedicines. [ABSTRACT FROM AUTHOR]

Rizatriptan (RZT) is an efficient anti-migraine drug which belongs to the class of selective 5 HT (1B/1D) serotonin receptor agonists. Nevertheless, RZT elicits several adverse effects and RZT nasal sprays have a limited half-life, requiring repeated doses that could cause patient noncompliance or harm to the nasopharynx and cilia. The current research aimed to develop orally disintegrating films (ODFs) of RZT employing maltodextrin (MTX) and pullulan (PUL) as film-forming polymers, as well as propylene glycol (PG) as a plasticizer. The ODFs were prepared by solvent casting method (SCM). The technique was optimized using Box–Behnken design (BBD), contemplating the ratios of PUL: MTX and different levels of PG (%) as factor variables. The influence of these factors was systematically analyzed on the selected dependent variables, including film thickness, disintegration time (D-time), folding endurance (FE), tensile strength (TS), percent elongation (%E), moisture content (%), and water uptake (%). In addition, the surface morphology, solid state analysis, drug content uniformity (%), drug release (%), and pH of the RZT-ODFs were also studied. The results demonstrated a satisfactory stable RZT-ODFs formulation that exhibited surface homogeneity and amorphous RZT in films with no discernible interactions between the model drug and polymeric materials. The optimized film showed a rapid D-time of 16 s and remarkable mechanical features. The in vitro dissolution kinetics showed that 100% RZT was released from optimized film compared to 61% RZT released from conventional RZT formulation in the initial 5 min. An animal pharmacokinetic (PK) investigation revealed that RZT-ODFs had a shorter time to achieve peak plasma concentration (Tmax), a higher maximum plasma concentration (Cmax), and area under the curve (AUC0−t) than traditional oral mini capsules. These findings proposed a progressive approach for developing anti-migraine drugs that could be useful in reducing the complications of dysphagia in geriatric and pediatric sufferers. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative musculoskeletal disorder affecting the whole synovial joint and globally impacts more than one in five individuals aged 40 and over, representing a huge socioeconomic burden. Drug penetration into and retention within the joints are major challenges in the development of regenerative therapies for OA. During the recent years, polymeric nanoparticles (PNPs) have emerged as promising drug carrier candidates due to their biodegradable properties, nanoscale structure, functional versatility, and reproducible manufacturing, which makes them particularly attractive for cartilage penetration and joint retention. In this review, we discuss the current development state of natural and synthetic PNPs for drug delivery and OA treatment. Evidence from in vitro and pre-clinical in vivo studies is used to show how disease pathology and key cellular pathways of joint inflammation are modulated by these nanoparticle-based therapies. Furthermore, we compare the biodegradability and surface modification of these nanocarriers in relation to the drug release profile and tissue targeting. Finally, the main challenges for nanoparticle delivery to the cartilage are discussed, as a function of disease state and physicochemical properties of PNPs such as size and surface charge. [ABSTRACT FROM AUTHOR]

With the rapid development of biomaterials and biotechnologies, various functional materials-based drug delivery systems (DDS) are developed to overcome the limitations of traditional drug release formulations, such as uncontrollable drug concentration in target organs/tissues and unavoidable adverse reactions. Polymer nanofibers exhibit promising characteristics including easy preparation, adjustable features of wettability and elasticity, tailored surface and interface properties, and surface-to-volume ratio, and are used to develop new DDS. Different kinds of drugs can be incorporated into the polymer nanofibers. Additionally, their release kinetics can be modulated via the preparation components, component proportions, and preparation processes, enabling their applications in several fields. A timely and comprehensive summary of polymeric nanofibers for DDS is thus highly needed. This review first describes the common methods for polymer nanofiber fabrication, followed by introducing controlled techniques for drug loading into and release from polymer nanofibers. Thus, the applications of polymer nanofibers in drug delivery were summarized, particularly focusing on the relation between the physiochemical properties of polymeric nanofibers and their DDS performance. It is ended by listing future perspectives. [ABSTRACT FROM AUTHOR]

Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anti-cancer drugs due to the lack of tumour-targeting activity in conventional pharmaceuticals. Poly(caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles have attracted significant attention as a potential drug carrier intended for human use. Since their first discovery, the Food and Drug Administration (FDA)-approved polymers have been studied extensively for various biomedical applications, specifically cancer therapy. The application of PCL-PEG micelles in different cancer therapies has been recorded in countless research studies for their efficacy as drug cargos. However, systematic studies on the effectiveness of PCL-PEG micelles of specific cancers for pharmaceutical applications are still lacking. As breast cancer is reported as the most prevalent cancer worldwide, we aim to systematically review all available literature that has published research findings on the PCL-PEG-based micelles as drug cargo for therapy. We further discussed the preparation method and the anti-tumour efficacy of the micelles. Using a prearranged search string, Scopus and Science Direct were selected as the databases for the systematic searching strategy. Only eight of the 314 articles met the inclusion requirements and were used for data synthesis. From the review, all studies reported the efficiency of PCL-PEG-based micelles, which act as drug cargo for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin's, delivery to various cancer sites. The drug's severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose–demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups' cappings with small molecular entities, as well as structural modifications of the SPIONs' surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs–based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs' magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs' versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development. [ABSTRACT FROM AUTHOR]

A microdevice that offers glucagon supplements in a safe, non‐invasive, and glucose‐responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold‐assisted microfabrication of biomedical materials or devices typically needs high‐resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing‐based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing‐assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose‐responsive transdermal glucagon microneedle patch through matrix volume change‐mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue‐induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post‐fabrication purifications of biomedical materials. [ABSTRACT FROM AUTHOR]

A suite of four drug deliverance formulations grounded on 5-fluorouracil enclosed in a chitosan-founded intercellular substance was produced by 3,7-dimethyl-2,6-octadienal with in situ hydrogelation. The formulations have been examined from a morphological and structural point of view by Fourier transform infrared (FTIR) spectroscopy and microscopy with polarized light, respectively. The polarized optical microscopy (POM) pictures of the three representative formulations obtained were investigated by fractal analysis. The fractal dimension and lacunarity of each of them were thus calculated. In this paper, a novel theoretical method for mathematically describing medicament deliverance dynamics in the context of the polymeric medicament constitution limit has been advanced. Assuming that the polymeric drug motion unfolds only on the so-called non-differentiable curves (considered mathematically multifractal curves), it looks like in a one-dimensional hydrodynamic movement within a multifractal formalism, the drug-release physics models are provided by isochronous kinetics, but at a scale of resolution necessarily non-differentiable. [ABSTRACT FROM AUTHOR]

Nanoparticles have been utilized in a variety of biomedical applications owing to their ability to achieve systemic stability and targeted drug delivery. In the present work, a new form of nanoparticle-embedded polymeric microbeads has been developed for controlled drug delivery applications. Copper nanoparticles are synthesized using copper sulfate pentahydrate via chemical reduction method. Using gelation technique microbeads are synthesized by combining copper nanoparticles with sodium alginate/badam gum polymeric matrix. The generated microbeads were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transition electron microscopy (TEM), selected area electron diffraction (SAED), and scanning electron microscopy (SEM). Ofloxacin used as model bioactive agent and studied the release and swelling studies at pH 2.0 and 7.4 at 37°C. Upon loading OFLX in to microbeads antibacterial activity were tested against S. mutans, K. pneumonia, and B. subtilis. The release kinetics and mechanism was analyzed by fitting the release data into different kinetic models and Korsmeyer–Peppas equation. [ABSTRACT FROM AUTHOR]

Optimal vision remains one of the most essential elements of the sensory system continuously threatened by many ocular pathologies. Various pharmacological agents possess the potential to effectively treat these ophthalmic conditions; however, the use and efficacy of conventional ophthalmic formulations is hindered by ocular anatomical barriers. Recent novel designs of ophthalmic drug delivery systems (DDS) using nanotechnology show promising prospects, and ophthalmic formulations based on nanotechnology are currently being investigated due to their potential to bypass these barriers to ensure successful ocular drug delivery. More recently, stimuli-responsive nano drug carriers have gained more attention based on their great potential to effectively treat and alleviate many ocular diseases. The attraction is based on their biocompatibility and biodegradability, unique secondary conformations, varying functionalities, and, especially, the stimuli-enhanced therapeutic efficacy and reduced side effects. This review introduces the design and fabrication of stimuli-responsive nano drug carriers, including those that are responsive to endogenous stimuli, viz., pH, reduction, reactive oxygen species, adenosine triphosphate, and enzymes or exogenous stimuli such as light, magnetic field or temperature, which are biologically related or applicable in clinical settings. Furthermore, the paper discusses the applications and prospects of these stimuli-responsive nano drug carriers that are capable of overcoming the biological barriers of ocular disease alleviation and/or treatment for in vivo administration. There remains a great need to accelerate the development of stimuli-responsive nano drug carriers for clinical transition and applications in the treatment of ocular diseases and possible extrapolation to other topical applications such as ungual or otic drug delivery. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the bloodbrain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Polymeric micelles (PMs) have made significant progress in drug delivery applications. A robust core–shell structure, kinetic stability and the inherent ability to solubilize hydrophobic drugs are the highlights of PMs. This review presents the recent advances and understandings of PMs with a focus on the latest drug delivery applications. The types, methods of preparation and characterization of PMs are described along with their applications in oral, parenteral, transdermal, intranasal and other drug delivery systems. The applications of PMs for tumor-targeted delivery have been provided special attention. The safety, quality and stability of PMs in relation to drug delivery are also provided. In addition, advanced polymeric systems and special PMs are also reviewed. The in vitro and in vivo stability assessment of PMs and recent understandings in this area are provided. The patented PMs and clinical trials on PMs for drug delivery applications are considered indicators of their tremendous future applications. Overall, PMs can help overcome many unresolved issues in drug delivery. [ABSTRACT FROM AUTHOR]

On-demand designed theranostics nanoagents show promising applications for next-generation precision-and-personalized oncotherapy. Researchers have since aimed to develop nanoplatforms that can efficiently deliver drugs and contrast medium to tumor and release active ingredients in response to tumor microenvironment (TME) conditions. Herein, we propose a modular strategy, and develop a series of nanoplatforms based on metal-coordinated-polyprodrugs for cancer theranostics. The polyprodrugs were synthesized through a click-reaction between amino acid and doxorubicin (DOX) with dipropiolate. The backbones of the polyprodrugs had intrinsic sensitivities to pH and/or GSH, and provided abundant -COOH, -NH2, or -S-S- to chelate with functional metal ions and further self-assembled to form different morphologies. Dicysteine, which contains disulfide bond (-S-S-), was chosen to copolymerize with DOX and triethylene glycol dipropiolate (TEP) to prepare the pH/GSH dual-responsive polyprodrug poly(dicysteine-co-TEP-co-DOX) (pDTD), then separately coordinated with Gd3+, Fe3+, and Mn2+ to construct nanoplatforms pDTD@M (M representing the metal ions). In vitro and in vivo investigations suggest the metal-coordinated-polyprodrug nanoplatforms have good magnetic resonance imaging (MRI) ability and efficient tumor-growth inhibition with high safety. The design strategy of nanoplatforms based on metal-coordinated-polyprodrugs provides a new idea for on-demand construction of promising theranostics agents. Compared to small molecule antitumor drugs, polymeric drugs have high drug loading ratio and are easily enriched at the tumor site to achieve improved therapy efficacy. This work utilizes click reactions to link amino acids with anticancer drugs to produce polymeric drugs that are degraded in response to tumor microenvironment and released small molecule antitumor drugs mainly in tumor sites, and subtly utilizes the coordination of amino acid to chelate MRI functional metal ion to realize enhanced MRI imaging mediated tumor therapy. This strategy provides a new idea for the convenient construction of polymeric drugs for tumor theranostics. [Display omitted] [ABSTRACT FROM AUTHOR]

Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2). It is used in the management and treatment of diabetes mellitus (type 2). Till now the research done suggests that nano delivery systems may be the choice of drug delivery which can reduce dosing frequency and improve patient compliance. Hence, it was proposed to prepare nanoparticles of Empagliflozin. In this work, it was attempted to prepare nanoparticles of Empagliflozin using Eudragit and HPMC as polymers by solvent evaporation technique. Among the formulations, F1 and F4 have exhibited the best results. Drug loading capacity was between 13.20 to 19.96 percent. Encapsulation efficiency (%) of drug-polymer containing nanoparticles in various ratios was in-between 68.38 to 95.82. It is increased as the polymer quantity increased. For 10 hours, in vitro dissolution testing showed the drug release percentage for all formulations in the range between 89.75 and 97.93 per cent. In vitro studies have concluded that nanoparticles of Eudragit are superior for Empagliflozin delivery than HPMC based nanoparticles. The polymeric nano particles were evaluated for anti-diabetic Activity. All the formulations showed optimum results of which formulation containing higher concentration of Eudragit shown the better results in all the evaluated parameters. The polymeric nano particles were evaluated by in-vitro and in-vivo anti-diabetic methods and shown potential anti-diabetic activity. Thus, F1 can be concluded as the ideal batch of formulation. [ABSTRACT FROM AUTHOR]