Polymeric Nanoparticles For Drug Delivery Research Articles

Polymeric Nanoparticles for Drug Delivery.

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.

Development of ciprofloxacin-loaded polymeric nanoparticles for drug delivery

Development of ciprofloxacin-loaded polymeric nanoparticles for drug delivery

HA-PEG-PCL Nanoparticles With Paclitaxel Loaded For Targeted Delivery To Colon Cancer

For improved treatment efficacy with no or few adverse effects and higher patient compliance, novel delivery techniques with selective dispersion are required. The biodegradable and biocompatible polymers hyaluronic acid (HA), polyethylene glycol (PEG), and polycaprolactone (PCL) were used to create paclitaxel-loaded nanoparticles. The development and characterisation of a Paclitaxel-loaded HA-PEG-PCL polymeric nanoparticulate drug delivery system were the goals of the current study work in order to increase the therapeutic efficacy and targeted Paclitaxel distribution. The copolymers were chemically created, and IR spectroscopies were used to identify them. Transmission electron microscopy, particle size, percentage of drug entrapment, cell viability studies, stability, and in vitro drug release profile were used to describe the nanoparticles' structure and morphology. To determine whether PTX was crystalline or amorphous inside the polymer matrix, experiments using differential scanning calorimetry and X-ray diffraction were also carried out. Zeta potentials for blank NPs and PTX-HA-PEG-PCL NPs were respectively -15.4±1.23 mV and -18±2.35 mV. In 144 hours, PTX-HA-PEG-PCL NPs demonstrated a 58.08±3.8 release of PTX at pH 7.4. Because HA functions as a ligand for the CD44 receptors that are over expressed on HT-29 cells, the PTX-HA-PEG-PCL NPs demonstrated noticeably more cytotoxicity as a result of better formulation internalization. The proposed nanotechnology’s-controlled drug release behavior showed its potential for colon cancer cell lines

Polymeric nanoparticles for drug delivery in glioblastoma: State of the art and future perspectives.

Glioblastoma (GBM) is an aggressive, fatal and malignant primary brain tumor. Despite the current standard treatment for glioblastoma patients including neurosurgical resection, followed by concomitant radiation and chemotherapy, the median survival rate is only about 15months. An unresolved challenge for current therapies is related to getting drugs through the blood-brain barrier (BBB), which hinders many chemotherapeutic agents from reaching tumors cells. Although a large amount of research has been done to circumvent the BBB and deliver drugs to the brain, with nanoparticles (NPs) taking the lead, the challenge is still high. In this regard, the BBB and how to transfer drug pathways through the BBB, especially using NPs, are introduced here. Afterwards, the latest advances in drug delivery, co-drug delivery, and combination modalities are described specifically for GBM treatments using natural and synthetic polymeric NPs and adjuvant therapies including hyperthermia, photodynamic therapy and also ketogenic regimens. In addition, receptor-mediated endocytosis agents that exist in endothelial capillary cells of the brain are explained. Lastly, future directions to finally deliver drugs through the BBB for GBM treatment are emphasized. It is the hope that this review can provide a number of practical pathways for the future development of BBB permeable nanochemotherapeutics against GBM.

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer's disease: Current trends and future perspectives.

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 blood-brain 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.

Development of salting-out extraction methodology for the determination of piroxicam from polymeric based nanocarriers and biological samples

The aim of the present study is to develop the polymeric nanoparticulate drug delivery systems of piroxicam and to evaluate the in-vitro characteristics such as entrapment efficiency, surface morphology, in-vitro drug release performance, etc. For this reason, a novel HPLC methodology was developed for the determination of piroxicam from its bulk form, pharmaceutical preparation, and nanoparticulate delivery systems. Furthermore, the developed formulation was applied to the rats and the biological samples (plasma, liver, heart, spleen, kidney, and lung homogenates) were analyzed by the developed HPLC method following a salting-out assisted liquid-liquid extraction strategy for the first time in the literature. A Kinetex C18 analytical column (150 mm × 4.6 mm i.d., 5 µm) was used as a stationary phase with a 0.8 mL/min flow rate of acetonitrile: phosphate buffer (40:60, v/v), the column oven was adjusted to 40 °C and detection wavelength is set to 360 nm. Developed method were validated as per selectivity, linearity, LOD, LOQ, precision, and accuracy specified in the International Council for Harmonisation guidelines. As a result of the present study, it has been shown that the analysis of piroxicam from the bulk form, pharmaceutical preparation, developed polymeric-based drug delivery system, and biological samples can be successfully performed and no interferences were observed in any matrix. The developed method was also successfully utilized to study the tissue distribution of piroxicam in rats.

Advantages of the use of polymeric nanoparticles in the treatment of breast cancer: a systematic review

Introduction:Breast cancer is responsible for a fifth of the total number of patients diagnosed with malignant neoplasms worldwide. Given the limitations of conventional treatments, studies are advancing to develop new therapies with more specificity and fewer side effects. Thus, the use of polymeric nanoformulations for the delivery of chemotherapeutic agents has been developed for biomedical applications. Objectives:therefore, the study aimed to investigate the advantages and effectiveness of the use of polymeric nanoformulations in drug delivery in relation to conventional therapies in the treatment of breast cancer. Method:bibliographic searches were performed using specific search strings, totaling 12 articles collected. Result:the results showed the effectiveness of the strategy of using polymeric nanoparticles for drug delivery, highlighting the increase in cellular uptake and sustained intracellular retention of drugs incorporated into the nanoparticles. It was evidenced that in addition to the increased efficacy, the safety and delivery of the drug improved. Conclusion:this strategy improved the performance of the drug, having a higher concentration of the active ingredient in the tissues of cancer patients, in addition to increasing the uptake and cellular concentration of the drug, as well as sustaining its intracellular retention, which increases the effectiveness of the treatment, due to its prolongation linked to the slow release and in smaller amounts of the drug.

Polymeric nanoparticles for dopamine and levodopa replacement in Parkinson's disease.

As the world's population ages, the incidence of Parkinson's disease (PD), the second most common neurological ailment, keeps increasing. It is estimated that 1% of the global population over the age of 60 has the disease. The continuous loss of dopaminergic neurons and the concomitant brain depletion of dopamine levels represent the hallmarks of PD. As a result, current PD therapies primarily target dopamine or its precursor (levodopa). Therapeutic approaches that aim to provide an exogenous source of levodopa or dopamine are hindered by their poor bioavailability and the blood-brain barrier. Nevertheless, the fabrication of many polymeric nanoparticles has been exploited to deliver several drugs inside the brain. In addition to a brief introduction of PD and its current therapeutic approaches, this review covers novel polymeric nanoparticulate drug delivery systems exploited lately for dopamine and levodopa replacement in PD.

Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy.

PurposeIn chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract’s hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells.MethodsfDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29.ResultsfDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and −1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such.ConclusionIn short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.

Targeted Polymeric Nanoparticles for Drug Delivery to Hypoxic, Triple-Negative Breast Tumors

High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA-diazobenzene-PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells' viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.

PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma.

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.

Collagen Nanoparticle-Mediated Brain Silymarin Delivery: An Approach for Treating Cerebral Ischemia and Reperfusion-Induced Brain Injury.

Silymarin is a bioactive constituent isolated from milk thistle (Silybum marinum). Since its discovery, silymarin has been considered a gold standard drug in treating ailments related to the liver, resulting from alcohol consumption and viral hepatitis. This hepatoprotective nature of silymarin arises out of antioxidative and tissue-regenerating properties of silymarin. However, several recent studies have established the neuroprotective link of silymarin, too. Thus, the current investigation was aimed at exploring the neuroprotective effect of nanosilymarin (silymarin encapsulated inside collagen-based polymeric nanoparticulate drug delivery system). The study aimed at bringing out the role of nanoparticles in enhancing the therapeutic effect of silymarin against neuronal injury, originating out of oxidative-stress-related brain damages in focal cerebral ischemia. Collagen-based micellar nanoparticles were prepared and stabilized using 3-ethyl carbodiimide-hydrochloride (EDC-Hcl) and malondialdehyde (MDA) as crosslinkers. Nanoparticles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy techniques, and the size of nanoparticles was found to be around 48 nm. Male albino Wistar rats were pretreated with three different doses of nanosilymarin of 10, 100, and 1,000 μg/kg b.wt and a dose of free silymarin of 100 mg/kg b.wt intraperitoneally (i.p.) for 7 days. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) model on the eighth day for 1 h followed by 24 h reperfusion. The animals were then evaluated for neurobehavioral, infarct analysis, biochemical, histopathological, and immunohistochemical studies. All the above parameters showed remarkable improvement in nanosilymarin-treated groups in comparison to the silymarin-treated group. Nanoparticle encapsulation of drug enhanced neuroprotection by increasing drug bioavailability and targeting. Thus, the present study concluded with satisfactory results, showing the critical role played by nanoparticles in improving the neuroprotection at very low drug doses.

Preparation and Surface Modification of Polymeric Nanoparticles for Drug Delivery: State of the Art.

Nanotechnology is one of the emerging fields in drug delivery for targeting the drug to the site of action. The polymeric nanoparticles as drug delivery systems have gained importance for the last few decades. They offer advantages over liposomes, dendrimers, emulsions etc. Surface engineering of polymeric nanoparticles is widely utilized to effectively target the cells in various diseases such as cancer, HIV infection. Surface modified nanoparticles offer various advantages such as targeted drug delivery, reduction in side effects, dose reduction and improved therapeutic efficacy. Moreover, they can aid in improving physical and biochemical properties, pharmacokinetic and pharmacodynamic profiles of the drug. Surface modified polymeric nanoparticles can provide targeted delivery of drugs into specific cells, especially when targets are intracellularly localized. This approach of surface modification would be more advantageous for the delivery of various anticancer, anti-inflammatory, anti-HIV drugs for more effective therapy. This review focuses on the techniques used for the fabrication of polymeric nanoparticles, the material used for surface modification and their applications.

Small molecules-PEG amphiphilic conjugates as carriers for drug delivery: 1. the effect of molecular structures on drug encapsulation

Conjugates of hydrophilic poly (ethylene glycol) and lipophilic small molecules could self-assemble into polymeric nanoparticles for drug delivery. Herein, three lipophilic molecules including pyrenebutyric acid (Pyr), cholic acid and dehydrocholic acid were immobilized on the terminal groups of methoxy PEG (mPEG) to obtain three amphiphilic conjugates. Four model drugs including β-carotene, naphthalene, doxorubicin hydrochloride (DOX‧HCl), and DOX were employed to study the impact of lipophilic structures in the conjugate on the drug loading capacities. The mPEG-Pyr nanoparticles showed the best drug loading capacity as well as encapsulation efficiency due to the intense interactions between payloads and pyrene. Although the loading contents of β-carotene, naphthalene, and DOX‧HCl were lower than 2%, the DOX loading content in DOX/mPEG-Pyr nanoparticles could be high as ca. 10%. The structure of small molecules in conjugates influenced the self-assembly behaviors and stability of drug-loaded nanoparticles. DOX/mPEG-Pyr showed a size of about 200 nm and the best stability in buffer. In vitro drug release study revealed that DOX was sustainedly released from DOX/mPEG-Pyr and the release speed was accelerated at acidic pH due to the improved solubility of DOX. Furthermore, the cellular uptake of DOX/mPEG-Pyr by HepG2 cells was faster than that of DOX/mPEG-Dcha, resulting in more efficient cancer cell inhibition. Our study revealed that the architectures of lipophilic moieties played an important role in the drug loading capacity, stability, and in vitro anticancer efficacy of PEG-small molecule conjugate nanoparticles.

Nanoparticles loaded in consumable polymeric oral films: A smart dosage form design for oral administration

This review article provides an overview of nanoparticles in polymeric oral thin films as smart, non-parenteral and noninvasive route of drug administration to achieve patient compliance for varied therapeutic applications. The increasing research trend towards developing biocompatible and biodegradable nanoparticles as sustained release mucoadhesive patches with potential to improve pharmacokinetics and bioavailability significantly has given impetus to drug repurposing of existing molecules to new boundaries. Most widely used polymers to prepare nanoparticles include alginate and chitosan as they are biodegradable, biocompatible, demonstrated low toxicity in in vitro and in vivo models and has already been approved for dietary use and wound dressing applications. Chitosan particularly has been used as a carrier for polymeric nanoparticles for drug delivery through various routes of administration. Nanoparticles (NP) prepared using chitosan and chitosan derivatives typically possess a positive surface charge and has mucoadhesive properties such that they can adhere to mucus membranes and release the drug in a sustained release manner. They have various applications for the treatment of cancer, gastrointestinal diseases, pulmonary diseases, drug delivery to the brain and ocular infections through non-parenteral route of drug delivery.

From adsorption to covalent bonding: Apolipoprotein E functionalization of polymeric nanoparticles for drug delivery across the blood-brain barrier.

The blood-brain barrier (BBB) is composed of brain endothelial cells, pericytes, and astrocytes, which build a tight cellular barrier. Therapeutic (macro)molecules are not able to transit through the BBB in their free form. This limitation is bypassed by apolipoprotein E (ApoE)-functionalized polymeric nanoparticles (NPs) that are able to transport drugs (e.g. dalargin, loperamide, doxorubicin, nerve growth factor) across the BBB via low density lipoprotein (LDL) receptor mediated transcytosis. Coating with polysorbate 80 or poloxamer 188 facilitates ApoE adsorption onto polymeric NPs enabling recognition by LDL receptors of brain endothelial cells. This effect is even enhanced when NPs are directly coated with ApoE without surfactant anchor. Similarly, covalent coupling of ApoE to NPs that bear reactive groups on their surface leads to significantly improved brain uptake while avoiding the use of surfactants. Several in vitro BBB models using brain endothelial cells or co-cultures with astrocytes/pericytes/glioma cells are described which provide first insights regarding the ability of a drug delivery system to cross this barrier. In vivo models are employed to simulate central nervous system-relevant diseases such as Alzheimer's or Parkinson's disease and cerebral cancer.

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects.

The complexity of some diseases—as well as the inherent toxicity of certain drugs—has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients—or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included.

PH-Responsive benzaldehyde-functionalized PEG-based polymeric nanoparticles for drug delivery: Effect of preparation method on morphology, dye encapsulation and attachment

Functionalized, pH-responsive and biocompatible polymeric nanoparticles have attracted the interest of many researchers working on novel pharmaceutical formulations. Here, in an effort to develop an efficient drug delivery formulation, all these properties are combined in one polymeric nanoparticle system. More specifically, benzaldehyde-functionalized amphiphilic block copolymers based on PEG-based oligo(ethylene glycol) methacrylate (OEGMA), benzaldehyde-containing para-formyl phenyl methacrylate (pFPMA) and pH-responsive 2-(diisopropyl)aminoethyl methacrylate (DPA) monomers are readily prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. pH-Switch and single emulsion-solvent evaporation post-polymerization processing methods are used to prepare benzaldehyde-functionalized PEGylated pH-responsive nanoparticles with diameters of 180–230 nm. After nanoparticle formation, the benzaldehyde groups on the surface are shown to react with an Alexa Fluor 488 hydroxylamine dye through oxime bond formation, illustrating the potential for these particles to be surface-functionalized with biologically important molecules, such as fluorescent dyes for tracking their intracellular fate or antibodies for targeted therapy. Encapsulation of Nile Red and rhodamine 6G dyes is performed during the post-polymerization processing step for nanoparticle formation. Nanoparticles with a fluorescent cargo were shown to be successfully internalized in both A2780 ovarian cancer and A549 lung epithelial human cells in vitro, further illustrating the potential for these formulations to be used as triggered release therapeutic drug delivery vehicles.

Alginate Nanoparticles for Drug Delivery and Targeting.

Nanotechnology refers to the control, manipulation, study and manufacture of structures and devices at the nanometer size range. The small size, customized surface, improved solubility and multi-functionality of nanoparticles will continue to create new biomedical applications, as nanoparticles allow to dominate stability, solubility and bioavailability, as well controlled release of drugs. The type of a nanoparticle, and its related chemical, physical and morphological properties influence its interaction with living cells, as well as determine the route of clearance and possible toxic effects. This field requires cross-disciplinary research and gives opportunities to design and develop multifunctional devices, which allow the diagnosis and treatment of devastating diseases. Over the past few decades, biodegradable polymers have been studied for the fabrication of drug delivery systems. There was extensive development of biodegradable polymeric nanoparticles for drug delivery and tissue engineering, in view of their applications in controlling the release of drugs, stabilizing labile molecules from degradation and site-specific drug targeting. The primary aim is to reduce dosing frequency and prolong the therapeutic outcomes. For this purpose, inert excipients should be selected, being biopolymers, e.g. sodium alginate, commonly used in controlled drug delivery. Nanoparticles composed of alginate (known as anionic polysaccharide widely distributed in the cell walls of brown algae which, when in contact with water, forms a viscous gum) have emerged as one of the most extensively characterized biomaterials used for drug delivery and targeting a set of administration routes. Their advantages include not only the versatile physicochemical properties, which allow chemical modifications for site-specific targeting but also their biocompatibility and biodegradation profiles, as well as mucoadhesiveness. Furthermore, mechanical strength, gelation, and cell affinity can be modulated by combining alginate nanoparticles with other polymers, surface tailoring using specific targeting moieties and by chemical or physical cross-linking. However, for every physicochemical modification in the macromolecule/ nanoparticles, a new toxicological profile may be obtained. In this paper, the different aspects related to the use of alginate nanoparticles for drug delivery and targeting have been revised, as well as how their toxicological profile will determine the therapeutic outcome of the drug delivery system.

Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery.

Drug delivery systems (DDS) based on functionalized polymeric nanoparticles have attracted considerable attention. Although great advances have been reported in the past decades, the fabrication efficiency and reproducibility of polymeric nanoparticles are barely satisfactory due to the intrinsic limitations of the traditional self-assembly method, which severely prevent further applications of the intelligent DDS. In the last decade, a new self-assembly method, which is usually called polymerization-induced self-assembly (PISA), has become a powerful strategy for the fabrication of the polymeric nanoparticles with bespoke morphology. The PISA strategy efficiently simplifies the fabrication of polymeric nanoparticles (combination of the polymerization and self-assembly in one pot) and allows the fabrication of polymeric nanoparticles at a relatively high concentration (up to 50 wt%), making it realistic for large-scale production of polymeric nanoparticles. In this review, the developments of PISA-based polymeric nanoparticles for drug delivery are discussed.