The interfacial structure of polymeric surfactant stabilised air-in-water foams.

Small-angle neutron scattering was used to probe the interfacial structure of nitrogen-in-water foams created using a series of tri-block polymeric surfactants of the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EOx-POy-EOx) range, from which the nature of the polymeric interface could be characterised. The data follow a pronounced Q(-4) decay, along with a number of inflexions and weak but well-defined peaks. These characteristics were well-described by a model embodying paracrystalline stacks of adsorbed polymer layers, whose formation is induced by the presence of the air-water interface, adsorbed at the flat air-water (film lamellae) interface. A minimum of approximately five paracrystalline polymer layers of thickness of the order of 85-160 Å, interspersed with somewhat thicker (400 Å) films of continuous aqueous phase were found to best fit the data. The thickness of the layer (L) was shown to follow a relationship predicted by anchor block dominated polymer adsorption theories from non-selective solvents, L ∼ EO(1)PO(1/3). The insight gained from these studies should permit a more rational design of polymeric stabilisers for hydrophilic polyurethane foams.

Retrospective descriptive analysis of an urban pediatric collaborative care program.

OBJECTIVE: The prevalence of mental health conditions in pediatric patients in the United States is approximately 15%. Concerningly, nearly half go untreated, with lower treatment rates among children of color. Collaborative care can increase access to care and has an emerging evidence base for pediatrics. We present retrospective results from a collaborative care program that accepted referrals for a variety of conditions. METHODS: Pediatric patients seen in an academic, urban collaborative care program from July 2019 to December 2021 were tracked in a registry. Demographics, presenting problem(s), symptoms, treatment, and discharge dispositions were examined. Descriptive data were analyzed, including changes in reported symptoms via paired t-tests. RESULTS: Three hundred nineteen patients were seen. Racial and ethnic diversity in our clinic's population was similar to that of the surrounding community, with half belonging to a minoritized racial or ethnic group. Symptom comparisons demonstrated clinically and statistically significant improvements from intake to discharge. CONCLUSION: Collaborative care can improve access to care and outcomes for a diverse pediatric population. Our clinic served racial and ethnic patient populations that were representative of the demographics of the metropolitan area. Further study is necessary to determine if collaborative care increases access for these underserved groups.

Long COVID in long-term care: a rapid realist review.

OBJECTIVES: The goals of this rapid realist review were to ask: (a) what are the key mechanisms that drive successful interventions for long COVID in long-term care (LTC) and (b) what are the critical contexts that determine whether the mechanisms produce the intended outcomes? DESIGN: Rapid realist review. DATA SOURCES: Medline, CINAHL, Embase, PsycINFO and Web of Science for peer-reviewed literature and Google for grey literature were searched up to 23 February 2023. ELIGIBILITY CRITERIA: We included sources focused on interventions, persons in LTC, long COVID or post-acute phase at least 4 weeks following initial COVID-19 infection and ones that had a connection with source materials. DATA EXTRACTION AND SYNTHESIS: Three independent reviewers searched, screened and coded studies. Two independent moderators resolved conflicts. A data extraction tool organised relevant data into context-mechanism-outcome configurations using realist methodology. Twenty-one sources provided 51 intervention data excerpts used to develop our programme theory. Synthesised findings were presented to a reference group and expert panel for confirmatory purposes. RESULTS: Fifteen peer-reviewed articles and six grey literature sources were eligible for inclusion. Eleven context-mechanism-outcome configurations identify those contextual factors and underlying mechanisms associated with desired outcomes, such as clinical care processes and policies that ensure timely access to requisite resources for quality care delivery, and resident-centred assessments and care planning to address resident preferences and needs. The underlying mechanisms associated with enhanced outcomes for LTC long COVID survivors were: awareness, accountability, vigilance and empathetic listening. CONCLUSIONS: Although the LTC sector struggles with organisational capacity issues, they should be aware that comprehensively assessing and monitoring COVID-19 survivors and providing timely interventions to those with long COVID is imperative. This is due to the greater care needs of residents with long COVID, and coordinated efficient care is required to optimise their quality of life.

In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy.

Prostate cancer (PCa), one of the leading causes of cancer-related deaths, currently lacks effective treatment for advanced-stage disease. Paclitaxel (PTX) is a highly active chemotherapeutic drug and the first-line treatment for PCa; however, conventional PTX formulation causes severe hypersensitivity reactions and limits PTX use at high concentrations. In the pursuit of high molecular weight, biodegradable, and pH-responsive polymeric carriers, one conjugates PTX to a polyacetal-based nanocarrier to yield a tert-Ser-PTX polyacetal conjugate. tert-Ser-PTX conjugate provides sustained release of PTX over 2 weeks in a pH-responsive manner while also obtaining a degree of epimerization of PTX to 7-epi-PTX. Serum proteins stabilize tert-Ser-PTX, with enhanced stability in human serum versus PBS (pH 7.4). In vitro efficacy assessments in PCa cells demonstrate IC50 values above those for the free form of PTX due to the differential cell trafficking modes; however, in vivo tolerability assays demonstrate that tert-Ser-PTX significantly reduces the systemic toxicities associated with free PTX treatment. tert-Ser-PTX also effectively inhibits primary tumor growth and hematologic, lymphatic, and coelomic dissemination, as confirmed by in vivo and ex vivo bioluminescence imaging and histopathological evaluations in mice carrying orthotopic LNCaP tumors. Overall, the results suggest the application of tert-Ser-PTX as a robust antitumor/antimetastatic treatment for PCa.

Low fluorine content CO2-philic surfactants.

The article addresses an important, and still unresolved question in the field of CO(2) science and technology: what is the minimum fluorine content necessary to obtain a CO(2)-philic surfactant? A previous publication (Langmuir 2002, 18, 3014) suggested there should be an ideal fluorination level: for optimization of possible process applications in CO(2), it is important to establish just how little F is needed to render a surfactant CO(2)-philic. Here, optimum chemical structures for water-in-CO(2) (w/c) microemulsion stabilization are identified through a systematic study of CO(2)-philic surfactant design based on dichain sulfosuccinates. High pressure small-angle neutron scattering (HP-SANS) measurements of reversed micelle formation in CO(2) show a clear relationship between F content and CO(2) compatibility of any given surfactant. Interestingly, high F content surfactants, having lower limiting aqueous surface tensions, γ(cmc), also have better performance in CO(2), as indicated by lower cloud point pressures, P(trans). The results have important implications for the rational design of CO(2)-philic surfactants helping to identify the most economic and efficient compounds for emerging CO(2) based fluid technologies.

Gelation or molecular recognition; is the bis-(α,ß-dihydroxy ester)s motif an omnigelator?

Understanding the gelation of liquids by low molecular weight solutes at low concentrations gives an insight into many molecular recognition phenomena and also offers a simple route to modifying the physical properties of the liquid. Bis-(α,ß-dihydroxy ester)s are shown here to gel thermoreversibly a wide range of solvents, raising interesting questions as to the mechanism of gelation. At gelator concentrations of 5-50 mg ml⁻¹, gels were successfully formed in acetone, ethanol/water mixtures, toluene, cyclohexane and chloroform (the latter, albeit at a higher gelator concentration). A range of neutron techniques - in particular small-angle neutron scattering (SANS) - have been employed to probe the structure of a selection of these gels. The universality of gelation in a range of solvent types suggests the gelation mechanism is a feature of the bis-(α,ß-dihydroxy ester) motif, with SANS demonstrating the presence of regular structures in the 30-40 Å range. A correlation between the apparent rodlike character of the structures formed and the polarity of the solvent is evident. Preliminary spin-echo neutron scattering studies (SESANS) indicated the absence of any larger scale structures. Inelastic neutron spectroscopy (INS) studies demonstrated that the solvent is largely unaffected by gelation, but does reveal insights into the thermal history of the samples. Further neutron studies of this kind (particularly SESANS and INS) are warranted, and it is hoped that this work will stimulate others to pursue this line of research.

Assessing Hand Hygiene and Low-Level Disinfection of Equipment Compliance in an Acute Care Setting: Mixed Methods Approach.

BACKGROUND: Hand hygiene and low-level disinfection of equipment behaviors among hospital staff are some of the leading cost-effective methods to reduce hospital-acquired infections (HAI) among patients. OBJECTIVE: The aim of this study is to examine hand hygiene and low-level disinfection of equipment practices in a central Texas hospital and to explore pertaining gaps, perceptions, and challenges. METHODS: Data were collected using a multipronged mixed methods approach that included the following: (1) observation of hand hygiene and low-level disinfection practices (12 and 8 units during morning and evening shifts, respectively); (2) observation of usability/placement of hand sanitizer dispensers; (3) semistructured interviews; and (4) a follow-up email survey. RESULTS: In total, 222 (156 morning shift and 66 evening shift) staff members were observed. Of 526 hand hygiene and 33 low-level disinfection opportunities, compliance was observed 410 (78%) and 17 (51%) times, respectively. Overall, 6 units (50%) had ≥0.80 (favorable) hand hygiene compliance during the morning shift and 2 units (25%) had ≥0.80 hand hygiene compliance during the evening shift. Aggregated low-level disinfection compliance was 0.54 during the morning and 0.33 during the evening. Overall, the odds of noncompliant hand hygiene behavior were 1.4 times higher among staff who worked during night shifts compared to day shifts; however, this relationship was not statistically significant (95% CI 0.86-2.18; P=.18). Noncompliant behavior was most likely among unit B staff during the evening; however, this relationship was not statistically significant (OR 5.3, 95% CI 0.84-32.9; P=.07) All units, except one, had similar hand sanitizer dispenser usability characteristics. In the qualitative part of the study, the following challenges were identified: "shortage of time while seeing patients," "sometimes the staff forgets," "concern about drying hands," "behavior is difficult or requires reminders," and "there may be issues with resources or access to supplies to perform these behaviors." Staff also stated that "a process that is considered effective is the Stop the Line program," and that the "behavior is easy and automatic." CONCLUSIONS: Hand hygiene and low-level disinfection compliance is dependent on several personal and nonpersonal factors. Issues such as time constraints, peer pressure, work culture, available resources, and understanding of guidelines could influence staff behavior. The information collected through this study can be used to re-examine similar or related issues at a larger scale.

Exploiting in situ NMR to monitor the formation of a metal-organic framework.

The formation processes of metal-organic frameworks are becoming more widely researched using in situ techniques, although there remains a scarcity of NMR studies in this field. In this work, the synthesis of framework MFM-500(Ni) has been investigated using an in situ NMR strategy that provides information on the time-evolution of the reaction and crystallization process. In our in situ NMR study of MFM-500(Ni) formation, liquid-phase 1H NMR data recorded as a function of time at fixed temperatures (between 60 and 100 °C) afford qualitative information on the solution-phase processes and quantitative information on the kinetics of crystallization, allowing the activation energies for nucleation (61.4 ± 9.7 kJ mol-1) and growth (72.9 ± 8.6 kJ mol-1) to be determined. Ex situ small-angle X-ray scattering studies (at 80 °C) provide complementary nanoscale information on the rapid self-assembly prior to MOF crystallization and in situ powder X-ray diffraction confirms that the only crystalline phase present during the reaction (at 90 °C) is phase-pure MFM-500(Ni). This work demonstrates that in situ NMR experiments can shed new light on MOF synthesis, opening up the technique to provide better understanding of how MOFs are formed.

Structural evolution in metallomicroemulsions - the effect of increasing alcohol hydrophobicity.

Small-angle neutron scattering and contrast variation has been employed to quantify how a series of alcohols with increasing hydrophobicity exert different abilities to structure a model toluene based metallomicroemulsion - a microemulsion system stabilised with a metallosurfactant. Classical microemulsion phase evolution and droplet structure are observed, leading to an oil rich core stabilised by a surfactant film containing a highly concentrated, hydrated metal ion layer.

Derivatizing weak polyelectrolytes--solution properties, self-aggregation, and association with anionic surfaces of hydrophobically modified poly(ethylene imine).

The physical properties of weak polyelectrolytes may be tailored via hydrophobic modification to exhibit useful properties under appropriate pH and ionic strength conditions as a consequence of the often inherently competing effects of electrostatics and hydrophobicity. Pulsed-gradient spin-echo NMR (PGSE-NMR), electron paramagnetic resonance (EPR), small-angle neutron scattering (SANS) surface tension, fluorescence, and pH titration have been used to examine the solution conformation and aggregation behavior of a series of hydrophobically modified hyperbranched poly(ethylene imine) (PEI) polymers in aqueous solution, and their interaction with sodium dodecylsulfate (SDS). PGSE-NMR gave a particularly insightful picture of the apparent molecular weight distribution. The presence of the hydrophobes led to a lower effective charge on the polymer at any given pH, compared to the (parent) nonmodified samples. Analysis of the SANS data showed that the propensity to form highly elliptical or rod-like aggregates at higher pHs, reflecting both the changes in protonation behavior induced by the hydrophobic modification and an hydrophobic interaction, but that these structures were disrupted with decreasing pH (increasing charge). The parent samples were not surface active yet the hydrophobically modified samples show pronounced surface activity and the presence of small hydrophobic domains. The surface activity increased with an increase in the degree of modification. On addition of SDS, the onset of the formation of polymer/surfactant complexes was insensitive to the degree of modification with the resultant PEI/SDS complexes resembling the size and shape of simple SDS micelles. Indeed, the presence of the SDS effectively nullifies the effects of the hydrophobe. Hydrophobic modification is therefore a viable option to tailor pH dependent properties, whose effects may be removed by the presence of surfactant.

Provider Perceptions of Treatment Options for Immature Permanent Teeth.

INTRODUCTION: Current treatment options for immature permanent teeth with pulpal necrosis include both apexification and regenerative endodontics. The purpose of this study was to survey endodontists on the use of these 2 treatment options. METHODS: Surveys were created by using Qualtrics and Teleform software and distributed by using the Salant and Dillman method. Endodontists (n = 1615) in 4 geographically and demographically diverse states, North Carolina, New York, Texas, and California, were surveyed. Data were analyzed by using descriptive statistics and χ2 analysis. Level of significance was set at 0.05. RESULTS: A 32.9% response rate was obtained. The majority of responders reported that apexification was the treatment of choice when considering the evidence base supporting the treatment (60%) and the predictability of treatment outcome (77.8%). Apexification was also the preferred treatment by 57.3% of respondents when asked to consider patient compliance, by 51.2% when considering the number of required patient appointments, and by 53.3% when considering the likelihood of tooth discoloration. Regenerative endodontics was reported as the preferred treatment by 89% of respondents when considering continued root development and by 66.7% when considering apical closure. The respondents' age and continuing education courses taken were significantly associated with their preferred treatment option. CONCLUSIONS: The results of our study indicate that endodontists consider both clinical and patient factors when treating immature teeth with pulpal necrosis. Increase in continuing education options may increase adoption of regenerative endodontic therapy.

Do model polymer therapeutics sufficiently diffuse through articular cartilage to be a viable therapeutic route?

The ability of a polymer therapeutic to access the appropriate subcellular location is crucial to its efficacy and is defined to a large part by the many and complex cellular biological and biochemical barriers such that a construct must traverse. It is shown here that model dextrin conjugates are able to pass through a cartilaginous extracellular matrix into chondrocytes, with little perturbation of the matrix structure, indicating that targeting of potential therapeutics through a cartilaginous extracellular matrix should be proven possible. Rapid chondrocytic targeting of drugs which require intra cellularisation for their activity and uniform extracellular concentrations of drugs with an extracellular target, is thus enabled though polymer conjugation.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity.

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency "burstlet" activity that probably is analogous to the previously described in vitro "fast rhythm", which is thought to represent lamprey locomotor activity. However, "burstlet" activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; "burstlet" activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, "burstlet" activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations.

Capturing "Extraordinary" Soft-Assembled Charge-Like Polypeptides as a Strategy for Nanocarrier Design.

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous "ordinary-extraordinary" phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor-localized as well as lymphotropic delivery.

Sir William Dunn (1833-1912): the man, his trust and his legacy to science and medicine.

William Dunn had no direct connections with medicine. He belonged to that Victorian generation of Scottish pioneers who went overseas to make their fortunes and, yet, devoted their money to numerous charitable purposes, mainly at home in the UK. His family origins were modest; born in Paisley, near Glasgow on 1 September 1833, he died in 1912 with an estate valued at 1.3 million pounds sterling. His fortune was made from a large worldwide trading empire with roots in South Africa, where he emigrated as a young man of 19--but later controlled from London. In his will, dated 4 November 1908, the key clause was 'to advance the cause of Christianity, to benefit children and young people, to support hospitals and alleviate human suffering, to encourage education and promote emigration'. After making provision for about half the total, he left the remainder in the hands of trustees. They allotted about 120 small sums to hospitals, nursing homes, orphanages and like institutions, but then decided that larger projects would be more likely to be permanent memorials to Sir William. After consulting the President of the Royal Society, Sir William Hardy, and the Secretary of the Medical Research Committee, Sir Walter Fletcher, the trustees gave 210,000 pounds sterling in 1920 to Sir Frederick Gowland Hopkins in biochemistry in Cambridge and 100,000 pounds sterling in 1922 to Professor Georges Dreyer in pathology in Oxford. Between them, these two laboratories have 'spawned' nine Nobel Prize winners. The 'alleviation of human suffering' achieved would surely have pleased Sir William and his trustees.

Photo-stabilised microemulsions.

Light-induced stabilisation of water-in-heptane microemulsions has been achieved with a UV-sensitive gemini photo-surfactant.

A small-angle neutron scattering study of biologically relevant mixed surfactant micelles comprising 1,2-diheptanoyl-sn-phosphatidylcholine and sodium dodecyl sulfate or dodecyltrimethylammonium bromide.

Small-angle neutron scattering (SANS) has been employed to characterize mixed micelles comprising the surfactants 1,2-diheptanoyl--phosphatidylcholine (DHPC)/sodium dodecyl sulfate (SDS) and 1,2-diheptanoyl--phosphatidylcholine (DHPC)/dodecyltrimethylammonium bromide (DTAB) using the classical model of a micelle consisting of a hydrocarbon core surrounded by a polar shell. Various constraints are applied to the data fitting, specifically the volume of the hydrocarbon core using the aggregation number determined from time-resolved fluorescence quenching (TRFQ) and the degree of micelle hydration as determined from an electron paramagnetic resonance (EPR) experiment. The morphologies of the DHPC/SDS and DHPC/DTAB mixed micelles are largely invariant with composition-as might be expected given the similarity in the tail volumes of the respective surfactants, and the observed behaviour of the aggregation number-with a radius comparable to the fully extended length of a dodecyl chain, the longer of the two hydrophobic moieties. The shell thickness is also largely invariant with composition, indicating that the phosphatidylcholine headgroup lies flat at the interface. For both cases, the degree of counter-ion dissociation extracted from the fitting of the SANS data increases significantly on addition of DHPC, in a manner very similar to that observed for related binary surfactant mixtures, provided there is only a small change in micelle aggregation number (micelle curvature). The coincidence of the degrees of counter-ion dissociation for these quite different systems suggests a common underlying behaviour in which the nonionic species merely dilutes the surface charge associated with the ionic headgroups.

Towards an understanding of adsorption behaviour in non-aqueous systems: adsorption of poly(vinyl pyrrolidone) and poly(ethylene glycol) onto silica from 2H, 3H-perfluoropentane.

The adsorption behaviour of low molecular weight poly(ethylene glycol) (PEG 600) and poly(vinyl pyrrolidone) (PVP K25) to silica particles has been investigated at room temperature (21 degrees C) in the partially fluorinated solvent 2H,3H-perfluoropentane (HPFP). PVP (absorbed amount, Gamma = 12 mg g(-1)) was found to adsorb more strongly than PEG (Gamma = 4 mg g(-1)). Both of these values were higher than observed in water. In a further distinction to the aqueous case, where PVP displaces PEG from the interface, no competitive adsorption effects were observed between these two polymers in HPFP, with the adsorbed amounts of each polymer being unchanged by the presence of the other. The stability of silica suspensions in HPFP was primarily dependent on the presence of PVP; PEG/silica systems were unstable, but PVP/silica and PEG/PVP/silica systems formed stable suspensions. All suspensions were destabilized by the addition of small (0.15 wt%) amounts of water. The observations made in this work would point to a flocculation phenomenon due to the addition of water, and not Ostwald ripening. The mechanism of this destabilization is likely to be water acting as a flocculation bridge between particles.

Explaining the phase behaviour of the pharmaceutically relevant polymers poly(ethylene glycol) and poly(vinyl pyrrolidone) in semi-fluorinated liquids.

Phase behaviour studies of low molecular weight poly(ethylene glycol) (denoted PEG 600 and PEG 1000, corresponding to molecular weights of 600 and 1000 g mol(-1), respectively) have been carried out in 2H,3H-perfluoropentane (HPFP) with and without added poly(vinyl pyrrolidone). The concentration and temperature dependencies of their phase behaviour and the effect of moisture on these systems have been established. Furthermore, the solubility of PEG 600 in binary mixtures of HPFP and perfluoropentane (PFP), as well as HPFP and perfluorodecalin (PFD) have been considered at high HPFP contents. A phase separation phenomenon in fluorinated non-aqueous media is reported for the first time: PEG 600 and PEG 1000 both show a lower critical solution temperature type phase separation boundary. The size of the PEGs was obtained from small-angle neutron scattering (radius of gyration) and pulsed-gradient spin-echo NMR (hydrodynamic radius) measurements. It is shown that polymer conformation follows a regular trend with solution concentration; the size increases from <10 A at 3 wt% in HPFP to 45 +/- 2 A at 20 wt% PEG. On changing the solvent composition by substitution of HPFP by PFP or PFD, the size decreases, consistent with a decrease in the hydrogen-bonding capacity of the solvent mixture. Computer modelling indicates an interaction between the PEG oxygen and the hydrogen of HPFP, an interaction that is absent for the fully fluorinated solvents. This indicates that hydrogen bonding is the driving force for polymer solubility in these solvents.

Polymer-doxycycline conjugates as fibril disrupters: an approach towards the treatment of a rare amyloidotic disease.

The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease, covalently linked to poly-l-glutamic acid (PGA). The conjugates were rationally designed, looking at drug loading and drug release rate by adequate linker design, always considering the physiological conditions at the molecular target site. Conjugation of doxycycline exhibited greater potential towards TTR fibril disaggregation in vitro compared to the parent drug. Exhaustive physico-chemical evaluation of these polymer-drug conjugates concluded that drug release was unnecessary for activity, highlighting the importance of an appropriate linker. Furthermore, biodistribution studies through optical imaging (OI) and the use of radiolabelled polymer-drug conjugates demonstrated conjugate safety profile and renal clearance route of the selected PGA-doxy candidate, settling the adequacy of our conjugate for future in vivo evaluation. Furthermore, preliminary studies in an FAP in vivo model at early stages of disease development showed non-organ toxicity evidences. This nanosized-system raises a promising treatment for advanced stages of this rare amyloidotic disease, and also presents a starting point for possible application within other amyloidosis-related diseases, such as Alzheimer's disease.