Degradable Alternating Copolymers by Radical Copolymerization of 2-Methylen-1,3-dioxepane and Crotonate Esters.

Producing backbone degradable copolymers via free-radical copolymerization is a promising, yet challenging method to develop more sustainable materials for many applications. In this work, we present the copolymerization of 2-methylen-1,3-dioxepane (MDO) with crotonic acid derivative esters. MDO can copolymerize by radical ring-opening polymerization incorporating degradable ester moieties in the polymer backbone, although this can often be difficult due to the very unfavorable reactivity ratios. Crotonic acid derivatives, on the other hand, can be easily produced completely from biomass but are typically very difficult to (co)polymerize due to low propagation rates and very unfavorable reactivity ratios. Herein, we present the surprisingly easy copolymerization between MDO and butyl crotonate (BCr), which shows the ability to form alternating copolymers. The alternating nature of the copolymer was characterized by MALDI-TOF and supported by the reactivity ratios calculated experimentally (rMDO = 0.105 and rBCr = 0.017). The alternating nature of the copolymers favored the degradability that could be achieved under basic conditions (in 2 h, all chains have molar masses smaller than 2 kg/mol). Last, the work was expanded to other crotonate monomers to expand the portfolio and show the potential of this copolymer family.

3D-printed boluses for radiotherapy: influence of geometrical and printing parameters on dosimetric characterization and air gap evaluation.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry.

Role of the Polymer Microstructure in Controlling Colloidal and Thermo-Responsive Properties of Nano-Objects Prepared Via RAFT Polymerization in a Non-polar Medium.

After having demonstrated their potential in biomedical applications, thermo-responsive block copolymers that are able to self-assemble into nano-objects in response to temperature modifications are becoming more and more appealing in other sectors, such as the oil and gas and lubricant fields. Reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly has been demonstrated as a valuable strategy for producing nano-objects from modular block copolymers in non-polar media, required for the mentioned applications. Although the influence of the nature and size of the thermo-responsive block of these copolymers on the properties of the nano-objects is extensively studied in the literature, the role of the solvophilic block is often neglected. In this work, we elucidate the role of the main microstructural parameters, including those of the solvophilic portion, of block copolymers produced by RAFT polymerization in the hydrocarbon blend decane/toluene 50:50 v/v on the thermo-responsive behavior and colloidal properties of the resulting nano-objects. Two long-aliphatic chain monomers were employed for the synthesis of four macromolecular chain transfer agents (macroCTAs), with increasing solvophilicity according to the number of units (n) or length of the alkyl side chain (q). Subsequently, the macroCTAs were chain-extended with different repeating units of di(ethylene glycol) methyl ether methacrylate (p), leading to copolymers that are able to self-assemble below a critical temperature. We show that this cloud point can be tuned by acting on n, p, and q. On the other hand, the colloidal stability, expressed in terms of area of the particle covered by each solvophilic segment, is only a function of n and q, which provides a way for controlling the size distribution of the nano-objects and to decouple it from the cloud point.

Health care-associated infections: Controlled delivery of cationic antiseptics from polymeric excipients.

Nowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented.

Synthesis and Characterization of a "Clickable" PBR28 TSPO-Selective Ligand Derivative Suitable for the Functionalization of Biodegradable Polymer Nanoparticles.

Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions. Several TSPO ligands have been developed and validated, so far. Among these, PBR28 has been widely adopted for PET imaging at both preclinical and clinical levels, thanks to its high brain penetration and high selectivity. For this reason, PBR28 represents a good candidate for functionalization strategies, where this ligand could be exploited to drive selective targeting of TSPO-expressing cells. Since the PBR28 structure lacks functional moieties that could be exploited for derivatization, in this work we explored a synthetic pathway for the synthesis of a PBR28 derivative carrying an alkyne group (PBR-alkyne), enabling the fast conjugation of the ligand through azide-alkyne cycloaddition, also known as click-chemistry. As a proof of concept, we demonstrated in silico that the derivatized PBR28 ligand maintains the capability to fit into the TSPO binding pocked, and we successfully exploited PBR-alkyne to decorate zwitterionic biodegradable polymer nanoparticles (NPs) resulting in efficient internalization in cultured microglia-like cell lines.

Limonene-in-water Pickering emulsion and on-demand separation using thermo-responsive biodegradable nanoparticles.

In the last few decades, Pickering emulsions have regained attention due to the possibility of forming stable oil-in-water emulsions with interesting interfacial properties. As an example, the more and more stringent regulations on the products for home and personal care are pushing the market towards the use of biodegradable materials in order to reduce their environmental impact. In this scenario, an appealing opportunity is offered by the use of biodegradable polymeric nanoparticles (NPs) for the stabilization of fragrance oils in water. In this work, modular biodegradable NPs have been synthesized through a combination of ring opening polymerization and reversible addition-fragmentation chain transfer emulsion polymerization and used to produce limonene-in-water Pickering emulsions. This strategy allowed controlling independently the NP size, polymer molecular weight, and hydrophobicity acting on the microstructure of the constituting copolymers. Stable limonene-in-water Pickering emulsions could be obtained, with the size of the oil phase and the wetting by limonene that can be strictly controlled by tuning the NP physico-chemical properties. Finally, the adoption of thermo-responsive polymer chains within the shell of the Pickering emulsifiers enabled the on-demand destabilization of the emulsions and hence the selective dispensing of limonene by simply increasing the temperature.

Influence of the Polymer Microstructure over the Phase Separation of Thermo-Responsive Nanoparticles.

Thermo-responsive nanoparticles (NPs), i.e., colloids with a sharp and often reversible phase separation in response to thermal stimuli, are coming to the forefront due to their dynamic behavior, useful in applications ranging from biomedicine to advanced separations and smart optics. What is guiding the macroscopic behavior of these systems above their critical temperature is mainly the microstructure of the polymer chains of which these NPs are comprised. Therefore, a comprehensive understanding of the influence of the polymer properties over the thermal response is highly required to reproducibly target a specific behavior. In this study, we synthesized thermo-responsive NPs with different size, polymeric microstructure and hydrophilic-lipophilic balance (HLB) and investigated the role of these properties over their phase separation. We first synthesized four different thermo-responsive oligomers via Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization of poly(ethylene glycol)methyl ether methacrylate. Then, exploiting the RAFT living character, we chain-extended these oligomers with butyl methacrylate obtaining a library of NPs. Finally, we investigated the NP thermo-responsive behavior, their physical state above the cloud point (Tcp) as well as their reversibility once the stimulus is removed. We concluded that the solid content plays a minor role compared to the relative length of the two blocks forming the polymer chains. In particular, the longer the stabilizer, the more favored the formation of a gel. At the same time, the reversibility is mainly achieved at high HLB, independently from the absolute lengths of the block copolymers.

A Graphene-Based Supramolecular Nanoreactor for the Fast Synthesis of Imines in Water.

The confinement of organic synthesis within waterborne nanoreactors is regarded with increasing attention to improve its yield and reduce the environmental impact. However, many catalysts, such as graphene, are barely dispersible in aqueous media and many chemical reactions cannot be performed in the presence of water due to thermodynamic limitations. Therefore, there is an urgent need to develop novel strategies to carry out these processes in more sustainable conditions. To pursue this goal, in this work, a waterborne supramolecular nanoreactor is developed. The system comprises a polymeric micelle obtained from the self-assembly of pyrrole-based amphiphilic block copolymers. The active catalytic component is represented by few graphene layers, functionalized with pyrrole to enhance their interaction with the micelle core and hence their nanoencapsulation. Using this nanoreactor, it is possible to synthesize imines starting from primary amines and aldehydes or ketones with high yield and in short time (Y = 90% after 5 min) at room temperature. Moreover, an efficient strategy to recycle the reactor is proposed, thus increasing the potential of this technology.

Current trends in the production of biodegradable bioplastics: The case of polyhydroxyalkanoates.

The global pollution caused by plastics and microplastics is stimulating intense research towards more environmentally friendly materials, preserving the remarkable application characteristics of the currently available polymers. Among these, polyhydroxyalkanoates (PHAs) have been hailed as the solution to replace conventional, oil-based plastics. Given their biodegradable nature and mechanical properties, their use can be envisioned in a wide range of applications reducing the environmental footprint. Several types of processes have been proposed for their production, which can be grouped in three main classes: (i) microbiological, (ii) enzymatic and (iii) chemical processes. Given the significant amount of literature available on this topic, this review aims to critically analyse what has been proposed so far in each of these classes, with specific reference to their potential to provide bioplastics that can actually replace the currently available materials. A comparison is made, based on the following aspects: achievable molecular structures (such as molecular weight and composition distributions), raw-material and production costs and availability of large-scale production technologies. Finally, some considerations and ideas on what should be further investigated and implemented to realize the economically sustainable production of PHA are brought forward.

Concentration of Polymer Nanoparticles Through Dialysis: Efficacy and Comparison With Lyophilization for PEGylated and Zwitterionic Systems.

Biodegradable polymeric nanoparticles (NPs) are attracting increasing attention as carriers for drug delivery. However, one of the main factors limiting their transition to the market is their premature degradation and release of the payload during the storage. Therefore, for increasing the formulation shelf-life, the removal of water is of paramount importance. In this work, we synthesized both polyethylene glycol (PEG)-stabilized and zwitterionic NPs via Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerization. We demonstrated that lyophilization leads the PEGylated NPs to irreversible aggregation, while the stability of the zwitterionic NPs was preserved only using a cryoprotectant. Therefore, we developed an alternative method for the NP concentration, based on the dialysis against a concentrated PEG solution. This method was optimized in terms of concentration factor (Fc), the ratio between the final and initial NP concentration, by acting on the PEG concentration in the dialysis medium, on its volume and on the initial NP concentration. With this approach, Fc up to 40 can be achieved in less than 10 h, preserving the possibility of redispersing the NPs to their original particle size distribution. Therefore, the dialysis proposed herein is a valuable alternative to lyophilization for the concentration of polymer NPs preserving their stability.

Surfactant-free and rinsing-resistant biodegradable nanoparticles with high adsorption on natural fibers for the long-lasting release of fragrances.

Synthetic polymers are attracting growing attention as additives for laundry and personal care products. In particular, the high volatility of many common fragrances requires the development of polymeric particles for their encapsulation and controlled release. Unfortunately, the vast majority of these carriers is made from polymers that are not biodegradable. This poses severe concerns about the accumulation of nano- and microplastics. Hence, such particles are expected to be banned from the market in the coming years. Therefore, biodegradable particles enabling a long-lasting release of the fragrances are urgently needed. In this work, we produced biodegradable nanoparticles (NPs) that are structurally composed of lactones, i.e. well known perfumes that occur naturally and that are already considered safe by regulatory agencies. We polymerized these lactones via ring opening polymerization (ROP) using an ionizable tertiary amine as initiator to produce in a single step amphiphilic oligoesters able to directly self-assemble into NPs once nanoprecipitated in water. In this way, we can produce biodegradable NPs with a perfume loading up to 85 % w/w without the need for additional surfactants. Subsequently we show that the ionizable group is able to confer a positive charge to our nanoparticles and, in turn, a high adsorption capacity on natural fibers (i.e. hairs and cotton fabric). Finally, we demonstrate the nanoparticle resistance to rinsing and their ability to confer a long-lasting fragrance perception to treated hair swatches for at least 3 weeks.

Readily Adsorbable Thermoresponsive Polymers for the Preparation of Smart Cell-Culturing Surfaces on Site.

The efficacy of several cell therapy products is directly impacted by trypsinization, which can diminish the engrafting capacity of transplanted cells by cleaving cell surface receptors. Thermoresponsive surfaces can alleviate this drawback, enabling temperature-driven and enzyme-free cell harvesting. However, the production of thermoresponsive surfaces relies on dedicated and complex equipment, often involving protocols dependent on high surface activation energies that prevent the development of scalable and universal platforms. In this work, we developed thermoresponsive copolymers incorporating styrene units that enable the copolymer adsorption on tissue culture polystyrene surfaces from an alcoholic solution in a short time, regardless of the vessel size and geometry, and without any particular equipment. In this way, the procedure can be performed with minimal effort by the end user on any surface. The thermoresponsive copolymers were synthesized via reversible addition-fragmentation chain transfer polymerization, providing high control over the polymer microstructure, a key parameter for tuning its cloud point and architecture. Block copolymers comprising a thermoresponsive segment and a polystyrene block exhibited optimal adhesion on conventional cell culture surfaces and permitted a more efficient temperature-mediated harvesting of adipose-derived stromal cells and Chinese hamster ovary cells compared to their statistical counterparts. To expand the application of this polymer deposition protocol to serum-free cell culture, we also considered the polymer modification with the tripeptide arginine-glycine-aspartic acid, known to promote the cell adhesion to synthetic substrates. The incorporation of this peptide enabled the collection in serum-free conditions of intact cell sheets from surfaces prepared shortly before their usage.

Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury.

Astrogliosis has a very dynamic response during the progression of spinal cord injury, with beneficial or detrimental effects on recovery. It is therefore important to develop strategies to target activated astrocytes and their harmful molecular mechanisms so as to promote a protective environment to counteract the progression of the secondary injury. The challenge is to formulate an effective therapy with maximum protective effects, but reduced side effects. In this study, a functionalized nanogel-based nanovector was selectively internalized in activated mouse or human astrocytes. Rolipram, an anti-inflammatory drug, when administered by these nanovectors limited the inflammatory response in A1 astrocytes, reducing iNOS and Lcn2, which in turn reverses the toxic effect of proinflammatory astrocytes on motor neurons in vitro, showing advantages over conventionally administered anti-inflammatory therapy. When tested acutely in a spinal cord injury mouse model, it improved motor performance, but only in the early stage after injury, reducing the astrocytosis and preserving neuronal cells.

Biodegradable zwitterionic nanoparticles with tunable UCST-type phase separation under physiological conditions.

Thermo-responsive polymeric nanoparticles (NPs) are emerging as a powerful tool in nanomedicine for the fabrication of advanced drug delivery systems. In addition to their size and biodegradation rate, phase separation of NPs upon application of a thermal stimulus provides an additional switch to control the rate of release of active components. Among the materials currently developed for biomedical applications, NPs stabilized by zwitterionic polymers are gaining increasing interest due to their high stability and ability to escape the body immune response. Yet, biodegradable zwitterionic NPs with temperature response under physiological conditions are currently not available. Here, we develop a new class of biodegradable zwitterionic NPs that exhibit UCST phase transition in the biological temperature range (T = 30-45 °C) and in physiological solution (i.e. 0.9% w/w NaCl). We design a strategy that relies on the self-assembly of block copolymers produced via reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. These copolymers comprise a zwitterionic portion exhibiting an upper critical solution temperature (UCST) and a biodegradable hydrophobic block consisting of oligoesters functionalized with a vinyl group. This modular macromolecular architecture allows us to independently control a variety of NP properties by modifying the individual components of the copolymer. In particular, the zwitterionic block of the copolymers controls the UCST-type phase separation behavior, while the number of the oligoester repeating units governs the size of the NPs and the length of the oligoester dictates the degradation rate. After demonstrating the synthesis of highly controlled degradable NPs, we show the potential of this new class of materials in the context of drug delivery by controlling the release of a drug-mimic molecule upon temperature variations in a broad time range from few minutes to 20 hours.

Thermo-responsive polymers: Applications of smart materials in drug delivery and tissue engineering.

Synthetic polymers are attracting great attention in the last decades for their use in the biomedical field as nanovectors for controlled drug delivery, hydrogels and scaffolds enabling cell growth. Among them, polymers able to respond to environmental stimuli have been recently under growing consideration to impart a "smart" behavior to the final product, which is highly desirable to provide it with a specific dynamic and an advanced function. In particular, thermo-responsive polymers, materials able to undergo a discontinuous phase transition or morphological change in response to a temperature variation, are among the most studied. The development of the so-called controlled radical polymerization techniques has paved the way to a high degree of engineering for the polymer architecture and properties, which in turn brought to a plethora of sophisticated behaviors for these polymers by simply switching the external temperature. These can be exploited in many different fields, from separation to advanced optics and biosensors. The aim of this review is to critically discuss the latest advances in the development of thermo-responsive materials for biomedical applications, including a highly controlled drug delivery, mediation of cell growth and bioseparation. The focus is on the structural and design aspects that are required to exploit such materials for cutting-edge applications in the biomedical field.

Biodegradable polymeric nanoparticles administered in the cerebrospinal fluid: Brain biodistribution, preferential internalization in microglia and implications for cell-selective drug release.

Cell-selective drug release in the central nervous system (CNS) holds great promise for the treatment of many CNS disorders but it is still challenging. We previously demonstrated that polymeric nanoparticles (NPs) injected intra-parenchyma in the CNS can be internalized specifically in microglia/macrophages surrounding the injection site. Here, we explored NPs administration in the cerebrospinal fluid (CSF) to achieve a wider spreading and increased cell targeting throughout the CNS; we generated new NPs variants and studied the effect of modifying size and surface charge on NPs biodistribution and cellular uptake. Intra-cerebroventricular administration resulted in prevalent localization of the NPs in proximity to stem-cell niches, such as around the lateral ventricles, the subventricular zone and the rostral migratory stream. NPs internalization occurred preferentially in brain myeloid cells/microglia. We demonstrated that brain biodistribution and extent of internalization in microglia are influenced by NPs dimensions and can be improved by applying a transient disruption of the blood-brain barrier with mannitol, leading to NPs internalization in up to 25% of brain myeloid/microglia cells. A fraction of the targeted cells was positive for markers of proliferation or stained positive for stemness/progenitor-cell markers such as Nestin, c-kit, or NG2. Interestingly, through these newly formulated NPs we obtained controlled and selective release of drugs otherwise difficult to formulate (such as busulfan and etoposide) to the target cells, preventing unwanted side effects and the toxicity obtained by direct brain delivery of the not encapsulated drugs. Overall, these data provide proof of concept of the applicability of these novel NP-based drug formulations for achieving internalization not only in mature microglia but also possibly in more immature myeloid cells in the brain and pave the way for brain-restricted microglia-targeted drug delivery regimens.

Self-Assembling PCL-Based Nanoparticles as PTX Solubility Enhancer Excipients.

The advent of nanotechnology in medicine has allowed to eliminate the toxic excipients that are often necessary to formulate lipophilic drugs in clinics. An example is paclitaxel, one of the most important chemotherapeutic drugs developed so far, where the Cremophor EL has been eliminated in the Genexol and Abraxane formulations. However, the complex procedures to synthesize these formulations hamper their cost-effective use and, in turn, their distribution among the patient population. For this reason, a simplified method to formulate this drug directly at the bed of the patient has been adopted. It requires only the use of a syringe and it starts from a native dry amphiphilic biodegradable and biocompatible block-copolymer obtained via the combination of the reversible addition-fragmentation chain transfer polymerization and ring-opening polymerization. In this way, a novel paclitaxel formulation with the same drug pharmacological properties, but without the use of the Cremophor EL, can be produced. In addition, as long as these nanoparticles are engineered to act as solubility enhancers, a lower burden for its approval from the pharmaceutical regulatory agencies is also expected.

Hydrazone linked doxorubicin-PLA prodrug nanoparticles with high drug loading.

An optimal drug delivery system should be characterized by biocompatibility, biodegradability, high drug loading and favorable drug release profile. To achieve this goal a hydrazone linked doxorubicin-poly(lactic acid) prodrug (PLA-DOX) was synthesized by the functionalization of a short polymer chain produced by ring opening polymerization. The hydrophobic prodrug generated in this way was nanoprecipitated using a block copolymer to form polymeric nanoparticles (NPs) with a quantitative loading efficiency and a high and tunable drug loading. The effects of the concentration of the PLA-DOX prodrug and surfactant were studied by dynamic light scattering showing a range of NP size between 50 and 90 nm and monodispersed size distributions with polydispersity indexes lower then 0.27 up to a maximum DOX concentration of 27% w/w. The release profile of DOX from these NPs, tested at different pH conditions, showed a higher release rate in acidic conditions, consistent with the nature of the hydrazone bond which was used to conjugate the drug to the polymer. In vitro cytotoxicity studies performed on BV2 microglia-like cell line highlighted a specific cytotoxic effect of these NPs suggesting the maintenance of the drug efficacy and a modified release profile upon encapsulation of DOX in the NPs.

Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin.

The improvement of the pharmacological profile of lipophilic drug formulations is one of the main successes achieved using nanoparticles (NPs) in medicine. However, the complex synthesis procedure and numerous post-processing steps hamper the cost-effective use of these formulations. In this work, an approach which requires only a syringe to produce self-assembling biodegradable and biocompatible poly(caprolactone)-based NPs is developed. The effective synthesis of monodisperse NPs has been made possible by the optimization of the block-copolymer synthesized via a combination of ring opening polymerization and reversible addition-fragmentation chain transfer polymerization. These NPs can be used to formulate lipophilic drugs that are barely soluble in water, such as trabectedin, a potent anticancer therapeutic. Its biodistribution and antitumor activity have been compared with the commercially available formulation Yondelis®. The results indicate that this trabectedin NP formulation performs with the same antitumor activity as Yondelis®, but does not have the drawback of severe local vascular toxicity in the injection site.

Synthesis and characterization of pH-sensitive drinkable nanoparticles for oral delivery of ibuprofen.

Ibuprofen (IBU) is a widespread drug used to treat both acute and chronic disorders. It is generally taken orally but the free drug can induce the irritation of the gastric mucosa due to its acid nature. In literature, different approaches have been adopted to prevent the release in the stomach, such as physical entrapment with film-coated tablets and drug-conjugates. Nevertheless, these solutions have many disadvantages, including the fast release of the drug and the difficulty to swallow the tablet, especially for children who may vomit or refuse the tablet. For this reason, in this work, novel formulations are proposed that do not require the encapsulation of the drug into a solid form and, in turn, their assumption as a pill. IBU has been linked to different types of methacrylates via ester bond in order to produce pH-responsive macromolecular monomers. The novelty is related to the use of these drug-conjugates macromonomer for the production of nanoparticles (NPs) via emulsion polymerization (EP), using water as solvent. The final emulsion is able to load up to 30 mg ml-1 of IBU, so less than 10 ml is required to be assumed to reach the minimum therapeutic dose of the drug (200 mg). Finally, the release of IBU from these novel drinkable formulations has been investigated in the gastric and intestinal simulated fluids to show the preferential release of IBU from the NPs in basic conditions. A comparison with an existing oral suspension has been performed to highlight the slower release in acid environment of these new formulations. Afterwards, the IBU loaded NPs were tested in vitro showing lower toxicity compared to the free drug.