Combined therapy can be a highly promising strategy efficacy in the treatment of cancer with minimum side effects. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has recently gained much attention due to its selective and localized therapeutic effects by light irradiation. The contrast agents for photo-based therapy should have a large absorption coefficient in the near-infrared region (NIR) (700–2500 nm) where the light has its maximum depth of penetration in tissues. In this work, we reported a multifunctional nanoparticle that has strong NIR absorbing capability for the combination of PTT and PDT. Methylene blue (MB) is a common photosensitizer for PDT in clinical use. Polypyrrole (PPy) is a super material for PTT because of its superior inherent features including strong NIR absorption, photothermal stability, low cost, and biocompatibility. For the first time, methylene blue (MB) was conjugated with photothermal material polypyrrole (PPy) to form a novel NIR photo-absorber. A fast and cost-effective method was developed to prepare the MB-PPy nanoparticles. The in vitro test evidenced that PPy–MB NPs able to kill the cancer cells with the assistance of the NIR laser. Therefore, the novel PPy–MB NPs could be considered as promising single multifunctional nanoplatforms for further applications of photo-induced therapy.

Electrospun biomaterials for in situ tissue regeneration are advantageous as drug delivery systems because they can be used to regulate the acute inflammatory response to establish a regenerative microenvironment. Neutrophils are the first inflammatory cell recruited to an electrospun biomaterial, and their release of neutrophil extracellular traps (NETs) and secretion of inflammatory and regenerative signals modulate the microenvironment around the biomaterial. In this work, chloroquine diphosphate, an anti-inflammatory drug shown to decrease NET release, was electrospun into polydioxanone (PDO) fibers for local delivery and immunomodulation of biomaterial-interacting neutrophils. Electrospinning was optimized so that the eluted concentration of chloroquine reached a previously reported, therapeutic concentration of 10 µM within one hour. Subsequently, acute neutrophil-template interactions were evaluated in vitro with freshly isolated human peripheral blood neutrophils for 3 and 6 hours. NET release was quantified through detection of NET-derived MPO with an ELISA, and the secretion of inflammatory and regenerative factors was quantified with an immunomagnetic multiplex assay. The results indicate that the chloroquine-eluting templates significantly reduced NET release within the first 3 hours, but had no effect at 6 hours, suggesting a therapeutic window for modulating acute NET release or temporal changes in cell viability. Additionally, the elution of chloroquine increased the secretion of regenerative factors HGF, VEGF-A, and IL-22 while suppressing inflammatory signals MMP-9 and IL-8 at 3 and 6 hours, indicating a shift towards a pro-healing neutrophil phenotype. Together, these data suggest that chloroquine-eluting PDO biomaterials may modulate the acute neutrophil response from inflammatory to pro-healing, which may significantly enhance in situ tissue regeneration. Future work includes in vivo studies to evaluate long-term effects on tissue integration and regeneration in a physiological environment. Ultimately, these electrospun biomaterials may function as immunomodulatory drug delivery systems that regulate the neutrophil response and enhance the potential for in situ tissue regeneration.

The aim of the following research work is to develop the n-propylgallate encapsulated solid lipid nanoparticles (PG-SLNs). And than loading of these PG-SLNs onto Hyaluronic acid based hydrogel suitable for intranasal delivery via applying Risk assessment and QbD methodology. Simple modified solvent injection technique was used for the preparation of the solid lipid nano-particles and response surface quadratic model was employed to get an optimized formulation. The developed nano-formulation (PG-SLNs) were characterized and loaded into Hyaluronic acid based hydrogel. In vitro release and permeation studies were also performed on optimized formulation. The PG-SLNs with an average size of 103±46.04 nm were obtained with PDI of 0.16±0.001, Zeta potential of -36±4.78 mv obtained with percentage yield of NPs was found to be 80.78±0.0125% and encapsulation efficiency was found to be 84±0.477% with loading capacity was about 60±0.034%. Characterization of hydrogel including pH, drug contents measurement, viscosity, swelling index etc studies were also performed. In vitro muco-adhesivity study, in vitro release and permeation study was also performed on final formulation. Release study describe diffusion based release kinetics from hydrogel. Permeation of these nano-carriers from hydrogel showed significant permeation of PG through artificial membrane. It can be concluded that PG-SLNs loaded hydrogel have potential to be delivered through intranasal route.

The creation of co-crystals as a route to create new pharmaceutical phases with modified or defined physicochemical properties is an area of intense research. Much of the current research has focused on creating new phases for numerous active pharmaceutical ingredients (APIs) to alter physical properties such as low solubilities, enhancing processability or stability. Such studies have identified suitable co-formers and common bonding motifs to aid with the design of new co-crystals but understanding how the changes in molecular structure of the components are reflected in the packing and resulting properties is still lacking. This lack of insight means that the design and growth of new co-crystals is still a largely empirical process with co-formers selected and then attempts to grow the different materials undertaken to evaluate the resulting properties. This work will report on the results of a combination of crystal structure database analysis with computational chemistry studies to identify what structural features are retained across a selection of families of co-crystals with common components. The competition between different potential hydrogen bonding motifs was evaluated using ab initio quantum mechanical calculations and this was related to the commonality in the packing motifs when observed. It is found while the stronger local bonding motifs are often retained within systems, the balance of weaker long range packing forces gives rise to many subtle shifts in packing leading to greater challenges in the prediction of final crystal structures.

Cyclodextrins (CDs) are cyclic oligosaccharides able to modify the solubility, stability and the aggregation behaviour of a large variety of molecules via complexation. Thanks to their water solubility and biocompatibility, CDs are particularly well-considered as building-blocks for the construction of nanodevices within the nanomedicine field, such as biomolecular sensors and gene/drug delivery systems. CDs have been widely utilized as pharmaceutical excipients and have been recently rediscovered as API in form of (2-hydroxypropyl)-β-cyclodextrin and Sugammadex.

In order to achieve specific purposes, these versatile sugars can be ad-hoc chemically modified with additional functionalities such as fluorescent moieties, photosensitive groups and units targeting biological systems. However, the controlled and regioselective functionalization is quite often challenging due to the large number of hydroxyl groups present on the macrocycles and the substantial differences in their reactivities according to their position on the ring. Thus, well-defined synthetic pathways must be thoroughly planned for each target derivative and the development of versatile synthetic procedures is highly desirable in this field.

In this contribution, the syntheses and the possible uses of CD-based fluorescent systems in imaging processes will be presented through several examples. In particular, the synthetic approaches towards rhodaminyl, fluoresceinyl, nitrobenzofuranyl and anthracenyl CD-based systems will be described and their applications in the visualization and/or targeting of biological process will be discussed.

The preparation of CD-based architectures combining molecules able to release singlet oxygen (¹O₂) and nitric oxide (NO) will be disclosed together with their utility in photodynamic therapy (PDT). In particular, the synergistic effect of modified CDs and photosensitizers such as porphyrins, xanthene dyes and trifluoromethyl-nitroanilines will be shown.

Green synthetic methods for the production of active-targeting delivery systems such as folate-appended CDs will be discussed and the manufacture of amphiphilic CDs for the effective stabilization and complexation of DNA and RNA will be elucidated. Finally, the syntheses of the two CD-based APIs, (2-hydroxypropyl)-β-cyclodextrin and Sugammadex will be analysed and examined with particular attention to the industrial scale-up.

Pterostilbene (3,5-dimethoxy-4¢-hydroxystilbene, PTB) is a natural dietary polyphenol, occurring primarily in blueberries and Pterocarpus marsupium heartwood. In recent years, this compound has attracted increasing interest owing to its antioxidant, anti-inflammatory and anticarcinogenic properties and its capacity to reduce and regulate cholesterol and sugar blood levels.

It is a methoxylated derivative of resveratrol, a class II compound in the Biopharmaceutics Classification System. The low aqueous solubility of pterostilbene is one factor that limits its utility, and among the different methods available for its improvement is its complexation with cyclodextrins (CDs), the subject of this study.

CDs are natural macrocyclic oligomers composed of a-D-glucose units linked by a-1,4 glycosidic bonds to form torus-shaped molecules. This conformation is responsible for inclusion complex formation with organic molecules, the latter generally being included within the hydrophobic CD cavity. In addition to enhancing the solubility of guest molecules, CD complexation can be used to improve other physicochemical properties such as stability, to prevent gastrointestinal irritation, to reduce or eliminate unpleasant odours and flavours, and to prevent drug-drug or drug-excipient interactions.

In this study, various methods used to prepare inclusion complexes between PTB and three natural cyclodextrins (a-CD, b-CD and g-CD) are described. In addition, the isolation of single crystals of complexes of PTB with b-CD and g-CD was pursued to determine the nature of their host-guest interactions using X-ray diffraction. The structure of a hydrated b-CD·PTB complex crystallizing in the monoclinic space group C2 was successfully resolved, revealing two disordered, diad-related PTB molecules encapsulated within a b-CD dimer. A microcrystalline product obtained by kneading g-CD and PTB was investigated by powder X-ray diffraction, which showed unequivocally that it is an inclusion complex crystallizing in the tetragonal space group P42₁2. Further characterization of these complexes was performed using thermogravimetry, differential scanning calorimetry and ¹H NMR spectroscopy.

Recent scientific publications have already demonstrated that co-grinding appears as an efficient, solvent-free technique for preparing cyclodextrin complexes and improving physicochemical properties of active ingredients. The improvement of solubility and dissolution rate could enhance the biopharmaceutical properties of the active ingredients in solid pharmaceutical products. Furthermore stable, amorphous, organic solvent-free inclusion complexes could be formed efficiently in the industrial environment. In this study terbinafine hydrochloride (TER), an antifungal BCS II drug was chosen as a model drug.

The aim of this study was the follow-through of inclusion complex preparation by co-grinding using several analytical methods.

TER and amorphous cyclodextrin derivatives (hydroxypropyl-β-cyclodextrin; heptakis(2,6-di-O-methyl)-β-cyclodextrin) were used for the preparation of products. The thermoanalytical behavior was analyzed by differential scanning calorimetry (DSC), the occurred changes in crystalline properties were investigated by X-ray powder diffractometry (XRPD) and hot-humidity stage X-ray powder diffractometry (HOT-XRPD). Chemical interactions between the components were analyzed by Raman spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Dissolution studies of TER and products were also carried out.

Cyclodextrin-TER complexes were prepared in the 1:1 molar ratio. DSC and XRPD studies suggested that the crystallinity of products gradually decreased by the increasing grinding time, and after 75 minutes of co-grinding the products were completely amorphous. HOT-XRPD studies revealed that the amorphous product containing hydroxypropyl-β-cyclodextrin did not change with increasing temperature. However, in the same process, the heptakis(2,6-di-O-methyl)-β-cyclodextrin containing product recrystallized in a new crystalline phase. Raman and FT-IR spectroscopy confirmed the molecular interactions between the components. Dissolution studies showed that the dissolution rate of complexes improved, and the solubility of TER increased both in simulated gastric and intestinal fluid, depending on the pH of the dissolution medium.

Iloperidone (Ilo) is a second-generation antipsychotic drug, is the first-line treatment, and approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and its derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) with the aim of improving its solubility and dissolution. Complexation was done by the kneading method. Characterization of SEβCD complexes with Iloperidone was done by FTIR, DSC, saturation solubility, etc. Multimedia dissolution of the complex was carried out and compared with the plain drug. Significant improvement in drug release was found from SEβCD complexes in all media when compared with drug alone.

Acknowledgment

This research was supported by the Science and Engineering Research Board, File Number: CRG/2018/003176. The authors would like to acknowledge the help provided by Cyclolab in the form of gift sample of SEBCD.

1) background: The desire to live longer lives demans novel strategies to perform this target. For that reason, in this work [1] the increase of the Caenorhabditis elegans (C.elegans) lifespan extension using hyper-branched cyclodextrin-based nanosponges (CD-NS) complexing oxyresveratrol (OXY) was evaluated. 2) Methods: The titration displacement of fluorescein was used to calculate the apparent complexation constant (K_F) between CD-NS and OXY. Moreover, PDE4 was expressed, purified and refolded in presence of cyclodextrins (CDs) to study its possible inhibition as pharmacological target of OXY. 3) Results: The effect of OXY on PDE4 displayed a competitive in vitro inhibition corroborated in silico. A maximum increase of the in vivo life expectancy of about 9.6% of using OXY/CD-NS complexes in comparison with the control was obtained without toxicity. 4) Conclusions: These results as a whole represent new opportunities to use OXY and CD-NS in lifespan products.

Montelukast sodium (MLK) is a worldwide anti asthmatic drug. Commercial formulations still have some issues with solubility and instability to light and humidity. To overcome them, the present work reports inclusion compounds of MLK and g-cyclodextrin (g-CD). As a molecular capsule, CDs have the ability to protect the inclusion guest from degradation, enhance its solubility and alter the pharmacokinetic parameters. MLK×g-CD inclusion compounds were prepared by mechanochemistry. Without using any solvent, g-CD was pre-milled and then co-milled with an equimolar quantity of MLK, in a ball mill at 600 cycles.min-1. After 120 min of milling, the formation of MLK·g-CD inclusion compounds was confirmed by powder X Ray diffraction and scanning electron microscopy. Additional studies, performed under Pharmacopeia guidelines, showed that the prepared MLK×g-CD inclusion compounds can indeed increase the dissolution of MLK drug when in ultra-pure water or simulated intestinal fluid (without pancreatin). This way, the MLK×g-CD inclusion compounds that are presented in this work are a promising solution for improving the therapeutic effectiveness of MLK drug.