Parkinson’s disease model in zebrafish using intraperitoneal MPTP injection

IntroductionParkinson’s disease (PD) is the second most common neurodegenerative disease that severely affects the quality of life of patients and their family members. Exposure to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reflect behavioral, molecular, and proteomic features of PD. This study aimed to assess the protocol for inducing PD following MPTP injection in adult zebrafish.MethodsFish were injected with 100 μg/g of MPTP intraperitoneally once or twice and then assessed on days 1 to 30 post-injection.ResultsBetween one-time and two-time injections, there was no significant difference in most locomotor parameters, expressions of tyrosine hydroxylase-2 (th2) and dopamine transporter (dat) genes, and dopaminergic neurons (tyrosine hydroxylase positive, TH+ cells) counts. However, caspase-3 levels significantly differed between one- and two-time injections on the day 1 assessment.DiscussionOver a 30-day period, the parameters showed significant differences in swimming speed, total distance traveled, tyrosine hydroxylase-1 (th1) and dat gene expressions, caspase-3 and glutathione protein levels, and TH+ cell counts. Days 3 and 5 showed the most changes compared to the control. In conclusion, a one-time injection of MPTP with delayed assessment on days 3 to 5 is a good PD model for animal studies

Supramolecular Luminescent Sensors

There is great need for stand-alone luminescence-based chemosensors that exemplify selectivity, sensitivity, and applicability and that overcome the challenges that arise from complex, real-world media. Discussed herein are recent developments toward these goals in the field of supramolecular luminescent chemosensors, including macrocycles, polymers, and nanomaterials. Specific focus is placed on the development of new macrocycle hosts since 2010, coupled with considerations of the underlying principles of supramolecular chemistry as well as analytes of interest and common luminophores. State-of-the-art developments in the fields of polymer and nanomaterial sensors are also examined, and some remaining unsolved challenges in the area of chemosensors are discussed

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

Photoactivatable (alternatively, photoremovable, photoreleasable, or photocleavable) protecting groups (PPGs), also known as caged or photocaged compounds, are used to enable non-invasive spatiotemporal photochemical control over the release of species of interest. Recent years have seen the development of PPGs activatable by biologically and chemically benign visible and near-infrared (NIR) light. These long-wavelength-absorbing moieties expand the applicability of this powerful method and its accessibility to non-specialist users. This review comprehensively covers organic and transition metal-containing photoactivatable compounds (complexes) that absorb in the visible- and NIR-range to release various leaving groups and gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide). The text also covers visible- and NIR-light-induced photosensitized release using molecular sensitizers, quantum dots, and upconversion and second-harmonic nanoparticles, as well as release via photodynamic (photooxygenation by singlet oxygen) and photothermal effects. Release from photo-activatable polymers, micelles, vesicles, and photoswitches, along with the related emerging field of photopharmacology, is discussed at the end of the review

Novel amphiphilic polymers from renewable feedstock: synthesis, characterisation and applications

Development of novel biodegradable polymers from renewable resources has attracted attention due to the limitations associated with polymers obtained from petroleum resources. The objective of the work presented in this thesis was to develop various novel biodegradable amphiphilic block copolymers from commercially available sustainable feedstocks for drug delivery applications. Synthesis was performed using a reported method under mild reaction conditions. Renewable δ-decalactone was chosen as a key monomer to synthesise novel amphiphilic block copolymers via ROP using PEG as initiator. A diblock (i.e. mPEG-b-PDL) and a triblock (i.e. PDL-b-PEG-b-PDL) copolymer of poly(decalactone) (PDL) was synthesised and purified successfully. Additionally, a novel triblock copolymer (i.e. mPEG-b-PDL-b-PPDL) was synthesised using ω-pentadecalactone as monomer and mPEG-b-PDL as initiator via ROP to generate a copolymer with different physical properties. Further, a di-block copolymer of ε-caprolactone (i.e. mPEG-b-PCL) was synthesised for comparative studies with novel block copolymers. Micelles of synthesised block copolymers were fabricated using a reported nanoprecipitation method. Micelles fabricated from these novel block copolymers were of sizes <200nm and possessed low critical micelle concentration (CMC) values. Curcumin and Amphotericin B were successfully encapsulated in the novel block copolymer micelles via nanoprecipitation method. The results obtained from curcumin loading and release studies suggested that these novel PDL block copolymers could perform in similar fashion when compared with poly(caprolactone) (PCL) block copolymer micelles. However, in subsequent study micelle of mPEG-b-PDL gave high loading content compared to mPEG-b-PCL micelles when amphotericin B was used as a drug. Further, a preliminary in vitro degradation study of mPEG-b-PDL micelles was performed and the results proposed that the ester linkage of PDL chain were susceptible to hydrolytic degradation in physiological condition. Additionally, in vitro cytotoxicity studies performed on HCT-116 human colon cancer cells revealed that the novel mPEG-b-PDL micelles have similar toxicity profiles when compared to the well-established mPEG-b-PCL micelles. Ligand mediated targeting efficiency of novel diblock copolymer micelles was also studied for potential future applications in cancer therapy. Amphiphilic block copolymers using PEG and PDL were synthesised via click chemistry to generate functionalised block copolymers. Folic acid and rhodamine B were used as targeting ligand and tracker dye respectively. Mixed micelles fabricated from functionalised block copolymers (i.e. FA-PEG-b-PDL, RhB-PEG-b-PDL and mPEG-b-PDL) were tested on folate receptor positive (MCF-7 FR+ve) and folate receptor negative (A549 FR-ve) human cancer cell lines for receptor mediated endocytosis. The acquired confocal images demonstrated the nonspecific uptake of the PEG-b-PDL micelles formulations (targeted and non-targeted) in both cell lines selected in current study. The results obtained from this thesis study suggested that the synthesised novel PDL block copolymer micelles have potential to act as a novel drug delivery system. However, further studies have been proposed to explore the possible applications of these renewable block copolymers

Novel amphiphilic polymers from renewable feedstock: synthesis, characterisation and applications

Development of novel biodegradable polymers from renewable resources has attracted attention due to the limitations associated with polymers obtained from petroleum resources. The objective of the work presented in this thesis was to develop various novel biodegradable amphiphilic block copolymers from commercially available sustainable feedstocks for drug delivery applications. Synthesis was performed using a reported method under mild reaction conditions. Renewable δ-decalactone was chosen as a key monomer to synthesise novel amphiphilic block copolymers via ROP using PEG as initiator. A diblock (i.e. mPEG-b-PDL) and a triblock (i.e. PDL-b-PEG-b-PDL) copolymer of poly(decalactone) (PDL) was synthesised and purified successfully. Additionally, a novel triblock copolymer (i.e. mPEG-b-PDL-b-PPDL) was synthesised using ω-pentadecalactone as monomer and mPEG-b-PDL as initiator via ROP to generate a copolymer with different physical properties. Further, a di-block copolymer of ε-caprolactone (i.e. mPEG-b-PCL) was synthesised for comparative studies with novel block copolymers. Micelles of synthesised block copolymers were fabricated using a reported nanoprecipitation method. Micelles fabricated from these novel block copolymers were of sizes <200nm and possessed low critical micelle concentration (CMC) values. Curcumin and Amphotericin B were successfully encapsulated in the novel block copolymer micelles via nanoprecipitation method. The results obtained from curcumin loading and release studies suggested that these novel PDL block copolymers could perform in similar fashion when compared with poly(caprolactone) (PCL) block copolymer micelles. However, in subsequent study micelle of mPEG-b-PDL gave high loading content compared to mPEG-b-PCL micelles when amphotericin B was used as a drug. Further, a preliminary in vitro degradation study of mPEG-b-PDL micelles was performed and the results proposed that the ester linkage of PDL chain were susceptible to hydrolytic degradation in physiological condition. Additionally, in vitro cytotoxicity studies performed on HCT-116 human colon cancer cells revealed that the novel mPEG-b-PDL micelles have similar toxicity profiles when compared to the well-established mPEG-b-PCL micelles. Ligand mediated targeting efficiency of novel diblock copolymer micelles was also studied for potential future applications in cancer therapy. Amphiphilic block copolymers using PEG and PDL were synthesised via click chemistry to generate functionalised block copolymers. Folic acid and rhodamine B were used as targeting ligand and tracker dye respectively. Mixed micelles fabricated from functionalised block copolymers (i.e. FA-PEG-b-PDL, RhB-PEG-b-PDL and mPEG-b-PDL) were tested on folate receptor positive (MCF-7 FR+ve) and folate receptor negative (A549 FR-ve) human cancer cell lines for receptor mediated endocytosis. The acquired confocal images demonstrated the nonspecific uptake of the PEG-b-PDL micelles formulations (targeted and non-targeted) in both cell lines selected in current study. The results obtained from this thesis study suggested that the synthesised novel PDL block copolymer micelles have potential to act as a novel drug delivery system. However, further studies have been proposed to explore the possible applications of these renewable block copolymers