Stiffness Modulation and Pulsatile Release in Dual Responsive Hydrogels.

Inspired by nature, self-regulation can be introduced in synthetic hydrogels by incorporating chemo-mechanical signals or coupled chemical reactions to maintain or adapt the material's physico-chemical properties when exposed to external triggers. In this work, we present redox and light dual stimuli responsive hydrogels capable of rapidly adapting the polymer crosslinking network while maintaining hydrogel stability. Upon irradiation with UV light, polymer hydrogels containing redox responsive disulfide crosslinks and light responsive ortho-nitrobenzyl moieties show a release of payload accompanied by adaptation of the hydrogel network towards higher stiffness due to in situ crosslinking by S-nitrosylation. Whereas the hydrogel design allows the network to either become softer in presence of reducing agent glutathione or stiffer upon UV irradiation, simultaneous application of both stimuli induces network self-regulation resulting in a pulsatile form of payload release from the hydrogel. Finally, adaptive stiffness was used to make tunable hydrogels as substrates for different cell lines.

Force-induced changes of α-catenin conformation stabilize vascular junctions independently of vinculin.

Cadherin-mediated cell adhesion requires anchoring via the ß-catenin-α-catenin complex to the actin cytoskeleton, yet, α-catenin only binds F-actin weakly. A covalent fusion of VE-cadherin to α-catenin enhances actin anchorage in endothelial cells and strongly stabilizes endothelial junctions in vivo, blocking inflammatory responses. Here, we have analyzed the underlying mechanism. We found that VE-cadherin-α-catenin constitutively recruits the actin adaptor vinculin. However, removal of the vinculin-binding region of α-catenin did not impair the ability of VE-cadherin-α-catenin to enhance junction integrity. Searching for an alternative explanation for the junction-stabilizing mechanism, we found that an antibody-defined epitope, normally buried in a short α1-helix of the actin-binding domain (ABD) of α-catenin, is openly displayed in junctional VE-cadherin-α-catenin chimera. We found that this epitope became exposed in normal α-catenin upon triggering thrombin-induced tension across the VE-cadherin complex. These results suggest that the VE-cadherin-α-catenin chimera stabilizes endothelial junctions due to conformational changes in the ABD of α-catenin that support constitutive strong binding to actin.

Design, synthesis and evaluation of biotin decorated inulin-based polymeric micelles as long-circulating nanocarriers for targeted drug delivery.

Here, long-circulating behaviors of Inulin-based nanomicelles are demonstrated for the first time in vivo. We show the synthesis and evaluation of biotin (BIO)-decorated polymeric INVITE micelles constituted of substances of natural origin, Inulin (INU) and Vitamin E (VITE), as long-circulating carriers for receptor-mediated targeted drug delivery. The resulting INVITE or INVITE-BIO micelles, nanometrically sized, did not reveal any cytotoxicity after 24h of incubation with Caco-2 cells. Moreover, in vitro studies on Caco-2 cells monolayers indicated that the transport of INVITE-BIO micelles was faster than surface unmodified INVITE micelles. In vivo optical imaging studies evidenced that, upon intravenous administration, INVITE-BIO micelles were quantitatively present in the body up to 48h. Instead, after oral administration, the micelles were not found in the systemic circulation but eliminated with the normal intestinal content. In conclusion, INVITE-BIO micelles may enhance drug accumulation in tumor-cells over-expressing the receptor for biotin through receptor mediated endocytosis.

Inulin-D-α-tocopherol succinate (INVITE) nanomicelles as a platform for effective intravenous administration of curcumin.

The aim of this work was to evaluate the potential of INVITE-based nanomicelles, an amphiphilic polymer constituted by inulin (INU) and vitamin E (VITE), as a platform for improving the biopharmaceutical properties of hydrophobic drugs. For this purpose, curcumin was selected as a model and curcumin-INVITE nanomicelles were prepared. This drug delivery system was characterized both in vitro for what concerns the physicochemical properties, blood compatibility, and cellular uptake, and in vivo for the evaluation of the pharmacokinetic profile. It was found that these nanomicelles released curcumin in a controlled manner, and they were able to penetrate cellular membrane. Moreover, they showed an improved pharmacokinetic profile after intravenous administration. In conclusion, INVITE micelles might constitute promising nanocarriers for improving the biopharmaceutical performance of hydrophobic drugs.

Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials.

Mucoadhesive properties and interaction with P-glycoprotein (P-gp) of thiolated-chitosans and -glycol chitosans and corresponding parent polymers: a comparative study.

The aim of the present work was to compare the mucoadhesive and efflux pump P-glycoprotein (P-gp) interacting properties of chitosan (CS)- and glycolchitosan (GCS)-based thiomers and corresponding unmodified parent polymers. For this purpose, the glycol chitosan-N-acetyl-cysteine (GCS-NAC) and glycol chitosan-glutathione (GCS-GSH) thiomers were prepared under simple and mild conditions. Their mucoadhesive characteristics were studied by turbidimetric and zeta potential measurements. The P-gp interacting properties were evaluated measuring the effects of thiolated- and unmodified-polymers on the bidirectional transport (BA/AB) of rhodamine-123 across Caco-2 cells as well as in the calcein-AM and ATPase activity assays. Although all the thiomers and unmodified polymers showed optimal-excellent mucoadhesive properties, the best mucoadhesive performances have been obtained by CS and CS-based thiomers. Moreover, it was found that the pretreatment of Caco-2 cell monolayer with GCS-NAC or GCS restores Rho-123 cell entrance by inhibiting P-gp activity. Hence, GCS-NAC and GCS may constitute new biomaterials useful for improving the bioavailability of P-gp substrates.

Symptomatic and asymptomatic long-term recurrences following transcatheter atrial fibrillation ablation.

BACKGROUND: Atrial fibrillation (AF) relapses, following transcatheter AF ablation, are frequently reported based on patients' symptoms, scheduled electrocardiograms (ECGs), or 24-hour Holter recordings. The aim of this study is to determine the incidence of asymptomatic and symptomatic AF recurrences, using continuous subcutaneous ECG monitoring, in the long-term follow-up of patients with paroxysmal or persistent AF undergoing transcatheter ablation. METHODS AND RESULTS: In total 113 consecutive patients symptomatic for paroxysmal or persistent AF were enrolled. All patients underwent pulmonary vein isolation plus left linear lesions. The insertable cardiac monitor (ICM), subcutaneously implanted during the ablation procedure, recorded the amount of AF per day (daily burden) and per last follow-up period (total AF burden). Based on symptoms and on scheduled 12-lead ECG performed during follow-up, 40 patients (35.4%) suffered AF recurrences. By means of ICM data, however, arrhythmia relapses were recorded within 75 patients (66.3%), of whom 35 (46.7%) were asymptomatic. Patients suffering symptomatic AF recurrences resulted, at univariate analysis, older (66.6 ± 8.4 years vs 61.6 ± 10.7 years) and suffering greater AF burden (88.8 ± 26.9% vs 8.0 ± 8.0%). CONCLUSIONS: AF ablation outcome based on patients' symptoms and/or scheduled ECGs underestimated relapses, as up to half of the patients, during a long-term follow-up, suffer asymptomatic recurrences.

Indications and contraindications of auditory brainstem implants: systematic review and illustrative cases.

The number of non-neurofibromatosis type 2 (NF2) indications for auditory brainstem implant (ABI) in the literature is increasing. The objective of this study was to analyze and discuss the indications for ABI. Retrospective chart review and systematic review were conducted at Quaternary referral skull base center and referring centers. Analysis of ABI cases with non-NF2 indications and systematic review presenting non-NF2 ABI cases were performed. Fourteen referred cases with ABI were identified. All cases had unsatisfactory results of ABI and all could have been rehabilitated with a cochlear implant (CI). Of these 14 cases, 9 improved with a cochlear implant, and 2 with a hearing aid, two are still planned for CI, one received bilateral CI, no ABI. In literature, we found 31 articles presenting 144 non-NF2 ABI cases with at least 7 different indications other than NF2. ABI should be restricted to those patients who have no other rehabilitation options. Patency of the cochlea and evidence of an intact cochlear nerve should be examined with imaging and electrophysiologic testing. Sometimes a CI trial should be planned prior to proceeding with ABI. We have shown that in many cases a CI is still possible and CI provided better results than ABI. In vestibular schwannoma in the only hearing ear, cochlear otosclerosis, temporal bone fractures, (presumed) bilateral traumatic cochlear nerve disruption, auto-immune inner ear disease and auditory neuropathy primarily CI are indicated. Traumatic bilateral cochlear nerve disruption is exceptionally unlikely. In cochlear nerve aplasia, testing should be performed prior to meeting indications for ABI. In malformations, ABI is indicated only in severe cochlear hypoplasia or cochlear aplasia.

Matrix Resistance Toward Proteolytic Cleavage Controls Contractility-Dependent Migration Modes During Angiogenic Sprouting.

Tissue homeostasis and disease states rely on the formation of new blood vessels through angiogenic sprouting, which is tightly regulated by the properties of the surrounding extracellular matrix. While physical cues, such as matrix stiffness or degradability, have evolved as major regulators of cell function in tissue microenvironments, it remains unknown whether and how physical cues regulate endothelial cell migration during angiogenesis. To investigate this, a biomimetic model of angiogenic sprouting inside a tunable synthetic hydrogel is created. It is shown that endothelial cells sense the resistance of the surrounding matrix toward proteolytic cleavage and respond by adjusting their migration phenotype. The resistance cells encounter is impacted by the number of covalent matrix crosslinks, crosslink degradability, and the proteolytic activity of cells. When matrix resistance is high, cells switch from a collective to an actomyosin contractility-dependent single cellular migration mode. This switch in collectivity is accompanied by a major reorganization of the actin cytoskeleton, where stress fibers are no longer visible, and F-actin aggregates in large punctate clusters. Matrix resistance is identified as a previously unknown regulator of angiogenic sprouting and, thus, provides a mechanism by which the physical properties of the matrix impact cell migration modes through cytoskeletal remodeling.

Slightly viscous dispersions of mucoadhesive polymers as vehicles for nasal administration of dopamine and grape seed extract-loaded solid lipid nanoparticles.

With the aim to find an alternative vehicle to the most used thermosensitive hydrogels for efficient nanotechnology-based nose-to-brain delivery approach for Parkinson's disease (PD) treatment, in this work we evaluated the Dopamine (DA) and the antioxidant grape seed-derived pro-anthocyanidins (Grape Seed Extract, GSE) co-loaded solid lipid nanoparticles (SLNs) put in slight viscous dispersions (SVDs). These SVDs were prepared by dispersion in water at low concentrations of mucoadhesive polymers to which SLN pellets were added. For the purpose, we investigated two polymeric blends, namely Poloxamer/Carbopol (PF-127/Carb) and oxidized alginate/Hydroxypropylmethyl cellulose (AlgOX/HPMC). Rheological studies showed that the two fluids possess Newtonian behaviour with a viscosity slightly higher that water. The pH values of the SVDs were mainly within the normal range of nasal fluid as well as almost no osmotic effect was associated to both SVDs. All the SVDs were capable to provide DA permeation through nasal porcine mucosa. Moreover, it was found that PF-127/Carb blend possesses penetration enhancer capability better than the Alg OX/HPMC combination. Flow cytometry studies demonstrated the uptake of viscous liquids incorporating fluorescent SLNs by human nasal RPMI 2650 cell in time-dependent manner. In conclusion, the SVD formulations may be considered promising alternatives to thermosensitive hydrogels strategy. Moreover, in a broader perspective, such SVD formulations may be also hopeful for treating various neurological diseases beyond PD treatment.

Targeting of the translocator protein 18 kDa (TSPO): a valuable approach for nuclear and optical imaging of activated microglia.

The aim of the present review is to give a concise and updated analysis of the imaging tools for the visualization of activated microglia. After an overview on the important pathologies where activated microglia are involved, we first describe the role played by the translocator protein-18 kDa (TSPO) as an important target for the visualization of activated microglia. Second, imaging tools based on TSPO ligands radiolabeled for positron emission tomography (PET) are summarized with particular emphasis to the TSPO ligands alternative to the standard radioligand [(11)C]PK11195 or (R)-[(11)C]PK11195. In this regard, an updated list of (11)C- and (18)F-labeled TSPO radioligands is shown. Moreover, a detailed analysis based on TSPO ligands bearing fluorescent probes for fluorescence microscopy is also provided. This last optical imaging technique represents an area of large and increasing interest due to the advantages offered by the use of simple instrumentation and safer experimental conditions. The scope and limitations of the nuclear and optical imaging techniques are discussed. Finally, a perspective on the plausible advances in this area is also presented.

Preoperative protective stenting of the internal carotid artery in the management of complex head and neck paragangliomas: long-term results.

OBJECTIVES: To investigate the long-term results of preoperative stenting of the internal carotid artery (ICA) in complex head and neck paragangliomas (HNP) as well as to report on indications and technical details of the procedure. METHOD: A comprehensive retrospective review of patients affected by HNP, consecutively operated on and preoperatively treated with stenting of the ICA in a quaternary referral skull base center, was performed. RESULTS: Nineteen patients affected by complex HNP were identified, on whom 21 preoperative stenting procedures were performed. The mean follow-up period after stent insertion was 53.8 months; the patients' age ranged from 33 to 56 years. Fourteen patients were affected by tympanojugular paragangliomas, 4 by vagal paragangliomas and 1 by bilateral carotid body tumors. Five patients presented with recurrent tumors, while 7 presented with multiple or bilateral HNP. There were no complications associated with endovascular procedures. Total tumor removal was accomplished in 52.4% of the cases with 1 recurrence. An advanced stage was the main factor conditioning total removal. Clinical control was obtained in 80% of the patients with residual disease. Total tumor removal from and around the ICA was obtained in 95.2% of the cases. Long-term stent patency was evident in 20 of 21 cases. CONCLUSIONS: Preoperative stenting of the ICA represents a safe and effective procedure in selected cases, obviating the need for balloon occlusion or bypass procedures and reducing the risk of intraoperative vascular injury.

Vestibular schwannoma in the only hearing ear: role of cochlear implants.

OBJECTIVES: We sought to delineate the role of cochlear implantation in the management of vestibular schwannoma or other cerebellopontine angle tumors in the only hearing ear. METHODS: We performed a retrospective analysis in a quaternary referral skull base center of all patients who were affected by vestibular schwannoma (or other lesions of the cerebellopontine angle) in the only hearing ear and received a cochlear implant before or after tumor treatment (surgery or radiotherapy) or during the wait-and-scan follow-up. We also performed a systematic review of the English-language literature. RESULTS: The clinical and audiological results of 10 patients are reported. All patients were managed with contralateral cochlear implantation. In 7 patients, cochlear implantation was performed before tumor removal, while hearing in the ear with the tumor was still present. In 3 patients, the implant was placed after curative surgery. Nine of the 10 patients routinely use their implant with subjective benefit and fairly good auditory performance (median disyllabic word recognition, 90%; median sentence comprehension, 75%). The literature search retrieved no major series with assessment of the long-term efficacy of cochlear implantation in this rare clinical scenario. CONCLUSIONS: Patients affected by vestibular schwannoma in their only hearing ear may significantly benefit from a cochlear implant on the contralateral side prior to tumor removal. Recent and significant hearing deterioration and tumor growth represent the main indications for cochlear implantation.

Tunable Synthetic Hydrogels to Study Angiogenic Sprouting.

Angiogenic sprouting, the formation of new blood vessels from pre-existing vasculature, is tightly regulated by the properties of the surrounding tissue microenvironment. Although the extracellular matrix has been shown to be a major regulator of this process, it is not clear how individual biochemical and mechanical properties influence endothelial cell sprouting. This information gap is largely due to the lack of suitable in vitro models that recapitulate angiogenic sprouting in a 3D environment with independent control over matrix properties. Here, we present protocols for the preparation of endothelial cell spheroid-laden synthetic, dextran-based hydrogels, which serve as a highly tunable 3D scaffold. The adjustment of the hydrogels' adhesiveness, stiffness, and degradability is demonstrated in detail. Finally, we describe assays to elucidate how individual matrix properties regulate angiogenic sprouting, including their analysis by immunofluorescence staining and imaging. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synthesis of methacrylated dextran (DexMA) Basic Protocol 2: Generation of endothelial cell spheroids in microwells Basic Protocol 3: Endothelial cell sprouting in hydrogels of tunable stiffness Basic Protocol 4: Endothelial cell sprouting in hydrogels of tunable adhesiveness Basic Protocol 5: Endothelial cell sprouting in hydrogels of tunable degradability Basic Protocol 6: Imaging of endothelial cell spheroid-laden hydrogels Support Protocol 1: Preparation of pro-angiogenic cocktail for endothelial cell sprouting.

Cavitating Lesions around the Cochlea Can Affect Audiometric Threshold and Clinical Practice.

There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disorder due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, we have collected five cases presenting this characteristic; their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the oval window (OW) away from the basilar membrane.

Carboxymethyl chitosan dopamine conjugates: Synthesis and evaluation for intranasal anti Parkinson therapy.

With respect to the Parkinson's disease (PD), herein, we aimed at synthetizing and characterizing two novel macromolecular conjugates where dopamine (DA) was linked to N,O-carboxymethyl chitosan or O-carboxymethyl chitosan, being both conjugates obtained from an organic solvent free synthetic procedure. They were characterized by FT-IR, 1H NMR spectroscopies, whereas thermal analysis (including Differential Scanning Calorimetry and Thermal Gravimetric Analysis) revealed good stability of the two conjugates after exposure at temperatures close to 300 °C. Release studies in simulated nasal fluid elucidated that a faster release occurred since O-carboxymethyl chitosan-DA conjugate maybe due to the less steric hindrance exerted by the polymeric moiety. The CMCS-DA conjugates prepared in aqueous medium may self-assembly to form polymeric micelles and/or may form polymeric nanoparticles. TEM and Photon correlation spectroscopy lent support for polymeric nanoparticle formation. Moreover, such CMCS-DA conjugates showed antioxidant activity, as demonstrated by DPPH radical scavenging assay. Finally, cytocompatibility studies with neuroblastoma SH-SY5Y cells showed no cytotoxicity of both conjugates, whereas their uptake increased from 2.5 to 24 h and demonstrated in 40-66 % of cells.

Novel Nanoparticles Based on N,O-Carboxymethyl Chitosan-Dopamine Amide Conjugate for Nose-to-Brain Delivery.

A widely investigated approach to bypass the blood brain barrier is represented by the intranasal delivery of therapeutic agents exploiting the olfactory or trigeminal connections nose-brain. As for Parkinson's disease (PD), characterized by dopaminergic midbrain neurons degeneration, currently there is no disease modifying therapy. Although several bio-nanomaterials have been evaluated for encapsulation of neurotransmitter dopamine (DA) or dopaminergic drugs in order to restore the DA content in parkinsonian patients, the premature leakage of the therapeutic agent limits this approach. To tackle this drawback, we undertook a study where the active was linked to the polymeric backbone by a covalent bond. Thus, novel nanoparticles (NPs) based on N,O-Carboxymethylchitosan-DA amide conjugate (N,O-CMCS-DA) were prepared by the nanoprecipitation method and characterized from a technological view point, cytotoxicity and uptake by Olfactory Ensheating Cells (OECs). Thermogravimetric analysis showed high chemical stability of N,O-CMCS-DA NPs and X-ray photoelectron spectroscopy evidenced the presence of amide linkages on the NPs surface. MTT test indicated their cytocompatibility with OECs, while cytofluorimetry and fluorescent microscopy revealed the internalization of labelled N,O-CMCS-DA NPs by OECs, that was increased by the presence of mucin. Altogether, these findings seem promising for further development of N,O-CMCS-DA NPs for nose-to-brain delivery application in PD.

The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells.

(1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in parkinsonian syndrome; (2) Methods: CIT-SLNs were prepared by the melt homogenization method using the self-emulsifying lipid Gelucire® 50/13 as lipid matrix. Solid-state features on CIT-SLNs were obtained with FT-IR, thermal analysis (DSC) and X-ray powder diffraction (XRPD) studies. (3) Results: CIT-SLNs showed a mean diameter of 201 nm, -2.20 mV as zeta potential and a high percentage of entrapped CIT. DSC and XRPD analyses evidenced a greater amorphous state of CIT in CIT-SLNs. On confocal microscopy, fluorescent SLNs replacing unlabeled CIT-SLNs released the dye selectively in the cytoplasm. Biological evaluation showed that pre-treatment of SH-SY5Y dopaminergic cells with CIT-SLNs (50 µM) before the addition of 40 µM 6-hydroxydopamine (6-OHDA) to mimic Parkinson's disease's degenerative pathways counteracts the cytotoxic effects induced by the neurotoxin, increasing cell viability with the consistent maintenance of both nuclear and cell morphology. In contrast, pre-treatment with CIT 50 and 60 µM or plain SLNs for 2 h followed by 6-OHDA (40 µM) did not significantly influence cell viability. (4) Conclusions: These data suggest an enhanced protection exerted by CIT-SLNs with respect to free CIT and prompt further investigation of possible molecular mechanisms that underlie this difference.

New fluorescent probes targeting the mitochondrial-located translocator protein 18 kDa (TSPO) as activated microglia imaging agents.

PURPOSE: To evaluate the utility of new Translocator protein 18 kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia. METHODS: Compounds 2-4 were synthesized; their stability and affinity for TSPO were determined. Compounds 2-4 were incubated both with Ra2 cells in the presence of LPS, a potent activator of microglia, and with tissue sections of normal and chemically injured brains. Compounds 2-4 were injected into carotid artery or directly in striatum of mice. Cells and tissue sections from these in vitro and in vivo studies were observed by fluorescence microscopy after histochemical treatments. RESULTS: Compounds 2-4 are stable in both buffer and physiological medium and showed high affinity for TSPO and were found to stain live Ra2 microglial cells effectively. Double staining with Mito Tracker Red suggested that binding sites of compounds 2 and 3 may exist on mitochondria. In vivo studies showed that compounds 2-4 may penetrate in part into brain; moreover, cells in mouse striatum were stained with compounds 2-4 and microglial marker CD11b. CONCLUSION: Compounds 2-4 can fluorescently label activated microglia in vitro and in vivo.

Griseofulvin/carrier blends: application of partial least squares (PLS) regression analysis for estimating the factors affecting the dissolution efficiency.

The main aim of the present study was to estimate the carrier characteristics affecting the dissolution efficiency of griseofulvin (Gris) containing blends (BLs) using partial least squares (PLS) regression analysis. These systems were prepared at three different drug/carrier weight ratios (1/5, 1/10, and 1/20) by the solvent evaporation method, a well-established method for preparing solid dispersions (SDs). The carriers used were structurally different including polymers, a polyol, acids, bases and sugars. The BLs were characterised at the solid-state by spectroscopic (Fourier transform infrared spectroscopy), thermoanalytical (differential scanning calorimetry) and X-ray diffraction studies and their dissolution behaviours were quantified in terms of dissolution efficiencies (log DE/DE(Gris)). The correlation between the selected descriptors, including parameters for size, lipophilicity, cohesive energy density, and hydrogen bonding capacity and log DE/DE(Gris) (i.e., DE and DE(Gris) are the dissolution efficiencies of the BLs and the pure drug, respectively) was established by PLS regression analysis. Thus two models characterised by satisfactory coefficient of determination were derived. The generated equations point out that aqueous solubility, density, lipophilic/hydrophilic character, dispersive/polar forces and hydrogen bonding acceptor/donor ability of the carrier are important features for dissolution efficiency enhancement. Finally, it could be concluded that the correlations developed may be used to predict at a semiquantitative level the dissolution behaviour of BLs of other essentially neutral drugs possessing hydrogen bonding acceptor groups only.