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Advanced polymeric controlled delivery systems are designed to effectively treat chronic diseases by adjusting the temporal profile of drug release. Most conventional controlled‐release carriers provide a constant and sustained‐release profile of therapeutics for an extended time. Although these systems have improved the patients’ compliance and adherence and have reduced the administration frequency, they cannot be used for optimal treatment of diseases that require variable patterns of drug release in the treatment regimen. These patterns and the specific rhythms of medical conditions determined by both the body's internal biological clock cycles (i.e., circadian rhythm) and each patient's characteristics call for patient‐specific controlled drug‐delivery systems that can provide adjustable drug release profiles. The importance of individualized therapy and the variety of biodegradable polymers with tunable physicochemical properties promote the design and manufacturing of polymeric delivery systems that release therapeutics at controllable rates. In the past two decades, novel biomaterials and fabrication methods have been utilized to improve the traditional drug‐delivery design and manufacturing technologies. This review article provides a critical discussion of emerging polymeric controlled‐release systems and the mechanisms through which they release their therapeutic agents. Advances and challenges in the design and the fabrication processes of polymeric drug‐delivery systems, particularly solid oral dosage forms and implantable microchips, with controllable release profiles of drugs, are reviewed, focusing on the application of microtechnology and 3D printing techniques in their manufacturing. The specific rhythms of medical conditions determined by the body's internal biological clock cycles (i.e., circadian rhythm) and each patient's characteristics call for patient‐specific drug‐delivery systems that can provide adjustable drug release profiles. The importance of individualized therapy and the variety of biodegradable polymers with tunable physicochemical properties promote the design and manufacturing of polymeric delivery systems that release therapeutics at controllable rates. This review article provides a critical discussion of emerging controlled‐release systems and the mechanisms through which they release their therapeutic agents. Advances and challenges in the design and the fabrication processes of drug‐delivery systems, particularly solid oral dosage forms and implantable microchips, with controllable release profiles of drugs, are reviewed, focusing on the application of microtechnology and 3D printing techniques in their manufacturing.

A series of hydrophilic copolymers were prepared using 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) from free radical polymerization at different feed monomer ratios using ammonium persulfate (APS) initiators in water at 70 °C. The herbicide 2,4-dichlorophenoxy acetic acid (2,4-D) was grafted to Poly(HEMA-co-IA) by a condensation reaction. The hydrolysis of the polymeric release system, Poly(HEMA-co-IA)-2,4-D, demonstrated that the release of the herbicide in an aqueous phase depends on the polymeric system’s pH value and hydrophilic character. In addition, the swelling behavior (Wt%) was studied at different pH values using Liquid-phase Polymer Retention (LPR) in an ultrafiltration system. The acid hydrolysis of the herbicide from the conjugates follows a first-order kinetic, showing higher kinetic constants as the pH increases. The base-catalyzed hydrolysis reaction of the herbicide follows a zero-order kinetic, where the basic medium acts as a catalyst, accelerating the release rate of the herbicide and showing higher kinetic constants as the pH increases. The differences in the release rates found for the hydrogel herbicide at different pH values can be correlated with the difference in their swelling capacity, where the release rate generally increases with an increase in the swelling capacity from water solution at higher pH values. The study of the release process revealed that all samples in distilled water at a pH of 10 are representative of agricultural systems. It showed first-order swelling kinetics and an absorption capacity that conforms to the parameters for hydrogels for agricultural applications, which supports their potential for these purposes.

An approach for providing feedback control for polypeptide drugs in a polymeric controlled-release system uses a trigger molecule and a polymer-bound enzyme that, in the presence of that trigger molecule, will cause an acid or a base to form. When the pH inside the polymer system changes, the solubility of the drug shifts dramatically, which changes the diffusion or dissolution driving force, and hence the release rate changes correspondingly. This concept was tested using a controlled-release system of ethylene/vinyl acetate copolymer containing insulin and immobilized glucose oxidase. The enzymatic reaction of glucose to gluconic acid reduces the pH in the polymer microenvironment. Since insulin solubility increases with decreasing pH (at physiologic pH, this is true for an insulin with an isoelectric point of 7.4 or higher), the release of insulin increases in response to glucose concentration. The feasibility of this concept has been shown using trilysyl insulin with an isoelectric point of 7.4. Multiple exposures to buffered glucose solutions over several weeks caused insulin release to reversibly increase during each exposure. Polymer-implanted diabetic rats infused with glucose solutions showed a significant increase in insulin concentration in 30 min--an effect not observed in three different sets of control rats.

In the last few decades, several natural bioactive agents have been widely utilized in the treatment and prevention of many diseases owing to their unique and versatile therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and neuroprotective action. However, their poor aqueous solubility, poor bioavailability, low GIT stability, extensive metabolism as well as short duration of action are the most shortfalls hampering their biomedical/pharmaceutical applications. Different drug delivery platforms have developed in this regard, and a captivating tool of this has been the fabrication of nanocarriers. In particular, polymeric nanoparticles were reported to offer proficient delivery of various natural bioactive agents with good entrapment potential and stability, an efficiently controlled release, improved bioavailability, and fascinating therapeutic efficacy. In addition, surface decoration and polymer functionalization have opened the door to improving the characteristics of polymeric nanoparticles and alleviating the reported toxicity. Herein, a review of the state of knowledge on polymeric nanoparticles loaded with natural bioactive agents is presented. The review focuses on frequently used polymeric materials and their corresponding methods of fabrication, the needs of such systems for natural bioactive agents, polymeric nanoparticles loaded with natural bioactive agents in the literature, and the potential role of polymer functionalization, hybrid systems, and stimuli-responsive systems in overcoming most of the system drawbacks. This exploration may offer a thorough idea of viewing the polymeric nanoparticles as a potential candidate for the delivery of natural bioactive agents as well as the challenges and the combating tools used to overcome any hurdles.

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.

Polymeric nanoparticles (PNPs) represent a groundbreaking advancement in targeted drug delivery, offering significant benefits over conventional systems. This includes their versatility, biocompatibility, and ability to encapsulate diverse therapeutic agents and provide controlled release, improving efficacy while minimizing side effects. The polymers used in PNP formulations are critical, as they influence the nanoparticles’ physicochemical properties such as size, shape, surface charge, and drug-loading capacity. Recent developments in polymer chemistry and nanotechnology have led to the creation of smart PNPs that can respond to specific stimuli, enabling precise drug release in targeted environments. This review explores the mechanisms of drug delivery, innovations in polymeric formulations, and the fabrication and characterization techniques that enhance drug delivery systems. Additionally, it discusses challenges and future directions in the field, highlighting the potential for personalized medicine and the role of artificial intelligence in optimizing nanoparticle design. By examining the relationship between polymer characteristics and PNP performance, the review aims to promote innovative therapeutic strategies in modern medicine. Despite the promise of polymer-based drug delivery systems, challenges such as toxicity, stability, scalability, and regulatory compliance must be addressed. Future research should focus on rigorous testing, clear risk communication, and sustainable practices to support clinical translation and commercial viability. Overall, the integration of these elements is crucial for advancing PNPs in therapeutic applications.

Nanoparticle systems integrating alginate and chitosan emerge as a promising avenue to tackle challenges in leveraging the potency of pharmacological active agents. Owing to their intrinsic properties as polysaccharides, alginate and chitosan, exhibit remarkable biocompatibility, rendering them conducive to bodily integration. By downsizing drug particles to the nano-scale, the system enhances drug solubility in aqueous environments by augmenting surface area. Additionally, the system orchestrates extended drug release kinetics, aligning well with the exigencies of chronic drug release requisite for antibacterial therapeutics. A thorough scrutiny of existing literature underscores a wealth of evidence supporting the utilization of the alginate-chitosan nanoparticle system for antibacterial agent delivery. Literature reviews present abundant evidence of the utilization of nanoparticle systems based on a combination of alginate and chitosan for antibacterial agent delivery. Various experiments demonstrate enhanced antibacterial efficacy, including an increase in the inhibitory zone diameter, improvement in the minimum inhibitory concentration, and an enhancement in the bacterial reduction rate. This enhancement in efficacy occurs due to mechanisms involving increased solubility resulting from particle size reduction, prolonged release effects, and enhanced selectivity towards bacterial cell walls, stemming from ionic interactions between positively charged particles and teichoic acid on bacterial cell walls. However, clinical studies remain limited, and there are currently no marketed antibacterial drugs utilizing this system. Hence, expediting clinical efficacy validation is crucial to maximize its benefits promptly.

The aim of the study was to design and formulate an antibody-mediated targeted, biodegradable polymeric drug delivery system releasing drug in a controlled manner to achieve a therapeutic goal for the effective treatment of breast cancer. Antibody-mediated paclitaxel-loaded PLGA polymeric nanoformulations were prepared by the solvent evaporation method using different experimental parameters and compatibility studies. The optimized formulations were selected for in vitro and in vivo evaluation and cytotoxicity studies. The in vitro drug release studies show a biphasic release pattern for the paclitaxel-loaded PLGA nanoparticles showing a burst release for 24 h followed by an extended release for 14 days; however, a more controlled and sustained release was observed for antibody-conjugated polymeric nanoparticles. The cytotoxicity of reference drug and paclitaxel-loaded PLGA nanoparticles with and without antibody was determined by performing MTT assay against MCF-7 cells. Rabbits were used as experimental animals for the assessment of various in vivo pharmacokinetic parameters of selected formulations. The pharmacokinetic parameters such as C max (1.18–1.33 folds), AUC 0-t (39.38–46.55 folds), MRT (10.04–12.79 folds), t 1/2 (3.06–4.6 folds), and V d (6.96–8.38 folds) have been increased significantly while clearance (4.34–4.61 folds) has been decreased significantly for the selected nanoformulations as compared to commercially available paclitaxel formulation (Paclixil ® ). The surface conjugation of nanoparticles with trastuzumab resulted in an increase in in vitro cytotoxicity as compared to plain nanoformulations and commercially available conventional brand (Paclixil ® ). The developed PLGA-paclitaxel nanoformulations conjugated with trastuzumab have the desired physiochemical characteristics, surface morphology, sustained release kinetics, and enhanced targeting.

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10–80 μg/ml), and MTT cytotoxic assay (concentration range of 10–90 μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

Scientists are focusing immense attention on polymeric nanocarriers as a prominent delivery vehicle for several biomedical applications including diagnosis of diseases, delivery of therapeutic agents, peptides, proteins, genes, siRNA, and vaccines due to their exciting physicochemical characteristics which circumvent degradation of unstable drugs, reduce toxic side effects through controlled release, and improve bioavailability. Polymers-based nanocarriers offer numerous benefits for in vivo drug delivery such as biocompatibility, biodegradability, non-immunogenicity, active drug targeting via surface modification, and controlled release due to their pH—and thermosensitive characteristics. Despite their potential for medicinal use, regulatory approval has been achieved for just a few. In this review, we discuss the historical development of polymers starting from their initial design to their evolution as nanocarriers for therapeutic delivery of drugs, peptides, and genes. The review article also expresses the applications of polymeric nanocarriers in the pharmaceutical and medical industry with a special emphasis on oral, ocular, parenteral, and topical application of drugs, peptides, and genes over the last two decades. The review further examines the practical, regulatory, and clinical considerations of the polymeric nanocarriers, their safety issues, and directinos for future research.