Design, Engineering and Biological Performance of Responsive Lipid Vesicles for Enhanced Drug Delivery by Mild Hyperthermia

The design of a delivery system that specifically delivers anticancer drug to the tumour site avoiding normal tissues damage has always been a challenge. In this thesis we describe the engineering and biological performance of novel temperature-sensitive liposomes (TSL) that have both a substantial in vivo stability and an efficient content-release by mild hyperthermia (HT). First, we explain the development of novel lipid-peptide hybrids (Lp-Peptide) by anchoring leucine zipper temperature-sensitive peptide within the liposomal lipid bilayer. We characterized this system by studying its physicochemical properties and the interaction of the peptide with the lipid bilayer. Then we examined its potential to retain and trigger the release of the anticancer drug, doxorubicin, in vitro at physiological temperatures and after exposure to mild HT. In addition, the blood kinetics, tumour and other tissues accumulation were explored when we studied the system in vivo. Our data suggested that Lp-Peptide hybrids can increase both immediate and long-term drug accumulation in the tumour. Therefore, we studied their therapeutic activity comparing two different heating protocols to mimic intravascular and interstitial drug release. The last chapter of this thesis explored the opportunities of increasing the therapeutic specificity of TSL by designing anti-MUC-1 targeted vesicles based on the traditional TSL (TTSL) to trigger drug release after specific uptake into cancer cells. The system was evaluated by studying the in vitro cellular binding, uptake and therapeutic efficacy. Taking this system a step further, its biodistribution and therapeutic potential were also examined. Different protocols were applied to explore the effect of HT on the accumulation of targeted TTSL into the tumour and their therapeutic efficacy. In summary, our studies demonstrate the critical factors to consider in the design of clinically relevant TSL and the importance of matching the heating protocol to their physicochemical and pharmacokinetic parameters to maximise therapeutic benefits

GERAKAN LINGKUNGAN DAN PARTAI POLITIK: STUDI TENTANG PERJUANGAN WALHI DALAM PEMBENTUKAN PARTAI HIJAU INDONESIA

Pendirian Partai Hijau Indonesia (PHI) dipandang sebagai kemajuan penting dari green politics politics, suatu gerakan dalam menciptakan tatanan kehidupan berkelanjutan yang berakar pada pelestarian lingkungan, keadilan sosial tanpa kekerasan, dan demokrasi kerakyatan/akar rumput. Artikel ini menganalisis peran dari organisasi gerakan lingkungan, yang dalam konteks ini adalah Wahala Lingkungan Hidup Indonesia (WALHI), dalam mendorong pembentukan PHI yang melibatkan kontestasi ideologi lingkungan di internal WALHI. Penelitian ini dibangun menggunakan pendekatan kualitatif dengan paradigma kritis. Data diperoleh melalui wawancara terhadap tokoh-tokoh WALHI, PHI, dan studi dokumentasi terkait proses pendirian PHI. Hasil penelitian ini mengungkapkan bahwa pendirian PHI oleh WALHI berasal dari pemikiran persoalan lingkungan yang terintegrasi dengan politik, ekonomi, sosial dan budaya. Buruknya produk politik dalam urusan tata kelola lingkungan menjadi dasar dan strategis untuk memperkuat green politics di Indonesia. Proses politik tersebut diharapkan melahirkan tata kelola lingkungan yang mengusung nilai-nilai sustainability. Dalam pendirian PHI, WALHI berperan sebagai kelompok kepentingan yang tidak memilih untuk melebur menjadi partai politik. Konsistensi WALHI dalam mempertahankan kedudukannya sebagai organisasi non pemerintahmembuat mereka lebih leluasa dalam melakukan kerja-kerja green politics. Namun, proses tersebut telah melalui serangkaian kontestasi ideologi di kalangan internal WALHI terutama di antara kelompok pro politik praktis dan kelompok pro gerakan lingkunga

The Effect of Different Storage Conditions for Refilled Plastic Drink Bottles on the Concentration of Microplastic Release in Water

The demand for water consumption in plastic bottles has increased in recent years. Most consumers of this type of water think that it is well sterilized. This is due to the high level of propaganda that accompanies its production regarding the extent of its validity. It is also common to reuse these bottles for several times by filling it frequently for different uses, and their use for preserving and storing different types of liquids. This study is conducted for the purpose of detecting and evaluating the pollution caused by microplastics in plastic bottles filled with water for one time, as well as water bottles reused more than once. Moreover, it evaluates the effect of storage period and conditions on the abundance of microplastics when bottles are stored for different times and under the influence of different conditions (shade, cooling and freezing). The results of the study show the presence of fine microplastics in open bottled water exposed to different storage conditions. The highest concentration of microplastics is obtained in storage conditions under the influence of shade with a limit of (1050) microplastics / liter, while the lowest concentration is obtained at around (20) microplastics / liter. The highest concentration of microplastics is obtained in storage conditions under the influence of cooling, with a limit of (850) microplastics / liter, whereas, the lowest concentration is obtained in the range of (16) microplastics / liter. Under the influence of freezing, the highest concentration of microplastics is obtained in the range of (648) microplasics / liter, while the lowest concentration Is obtained in the range of (20) microplastics / liter. Through the results, it is noted that there is a noticeable gradient in the concentration of microplastics for the samples that have been studied. It is also noted that there is an increase in the concentration of microplastics with repeated reuse during continuous periods of time. It is recommended that more studies and research be conducted indicating the extent of the impact of microplastics on human health in addition to other environmental components with emphasis on finding treatment means to get rid of microplastics

Analysis of Oxygen Transfer Performance on Sub-surface Aeration Systems

Abstract: The efficiency of oxygen transfer depends on many factors including the type, size and shape of diffusers and the tank geometry. In this paper, the effect of the depth of water in the tank and, the extension of coverage area of diffusers on each of oxygen transfer capacity (OC), efficiency (E) and, on a percentage of oxygen absorption (δ) is tested. Experimental procedure is adopted to evaluate the effect of these parameters. The results of the study showed that, both the depth of water and the extent of coverage area of diffuser had a significant effect on the tested parameters. The values of oxygen transfer capacity (OC) and efficiency (E) ranged from 18 to 170 grO 2 /m 3 . hr and from 2 to 17 grO 2 /m 3 air, respectively; depending on the depth of water in tank and the ratio of diffusers coverage area. The percentage of oxygen absorption ranged from 0.45-5.4% depending on the testing conditions. Specific mathematical models to .describe the effect of each parameter were also derived. The exponential form of equation proved to be efficient in describing the effect of a depth water on oxygen transfer capacity (OC) whereas; the linear form of equation was good enough in representing the effect of the other parameters

Batch studies on the removal of Ni (II) from aqueous solution by Azolla filiculoides

There are many plants which have the ability to accumulate large amounts of heavy metals and one of them is the aquatic fern, Azolla filiculoides. Toxic metals constitute a serious health risk because they accumulate in soils, water and organisms. One of the methods for removing these pollutants from water and soil is the use of plants. The aim of this study was to test the ability of A. filiculoides to adsorb Ni from polluted waters. The maximum uptake of nickel ions by the collected A. filiculoides biomass under the optimal conditions was approximately 45.32 mg/g dry Azolla. Desorption experiments indicated that EDTA was an efficient desorbent for recovery from nickel ions.Key words: Nickel, Azolla filiculoides, wastewater, biosorption

Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles

Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the ‘protein corona’ and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post-injection of liposomes into CD-1 mice. The results demonstrated that a complex protein corona was formed as early as 10 min post-injection. Even though the total amount of protein adsorbed did not significantly change over time, the fluctuation of protein abundances observed indicated highly dynamic protein binding kinetics

Engineering thermosensitive liposome-nanoparticle hybrids loaded with doxorubicin for heat-triggered drug release

The engineering of responsive multifunctional delivery systems that combine therapeutic and diagnostic (theranostic) capabilities holds great promise and interest. We describe the design of thermosensitive liposome-nanoparticle (NP) hybrids that can modulate drug release in response to external heating stimulus. These hybrid systems were successfully engineered by the incorporation of gold, silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid membranes without compromising doxorubicin loading and retention capability. The presence of metallic NPs in the lipid bilayer reinforced bilayer retention and offered a nanoparticle concentration-dependent modulation of drug release in response to external heating. In conclusion, LTSL-NP hybrids represent a promising versatile platform based on LTSL liposomes that could further utilize the properties of the embedded NPs for multifunctional theranostic applications

Fuzzy Retractions of Fuzzy Open Flat Robertson-Walker Space

Our aim in the present paper is to introduce and study new types of fuzzy retractions of fuzzy open flat Robertson-Walker model. New types of the fuzzy deformation retracts of model are obtained. The relations between the fuzzy foldings and the fuzzy deformation retracts of model are deduced. Types of fuzzy minimal retractions are also presented. New types of homotopy maps are deduced. New types of conditional fuzzy folding are presented. Some commutative diagrams are obtained

Post-Surgical Repair of Cleft Scar Using Fractional CO2 Laser

BACKGROUND: Postoperative scarring is a common cause of patients dissatisfaction. Several modalities have been developed to overcome such a problem following surgical repair. Despite precise surgical technique, still, some scars would remain over the time, mostly due to the weak formation or inadequately replaced collagen fibres in the underneath dermis especially those following unilateral or bilateral cleft lip repair surgery.AIM: of this study is to evaluate whether a 10,600 nm fractional ablative carbon dioxide (CO2) used early during the healing period would result in better postoperative scars.METHODS: In the present study six patients complained from cleft lip scars resulting from lip revision surgery. Each patient had six fractional ablative CO2 laser sessions for treatment along six months to obtain a complete collagen cycle. Vancouver Scar Scale VSS was used as a method of evaluation of the scar using 4 points scale evaluating vascularity, pliability, thickness & colour of the skin and Visual Analogue Scale VAS from (0-10) was used to assess the severity of pain as well as a survey questionnaire for the rate of patient’s satisfaction. Also, digital clinical photos assessment before&after were compared.RESULTS: Patients expressed a significantly greater degree of satisfaction with the treatment using a subjective 4-point scale. All patients observed dramatic improvement in their lip scars after FCO2 laser sessions following their surgeries with the better psychological state. The assessment was done by clinical observation according to VSS before (9.17 ± 2.2) while after (3.33 ± 1.9) with a highly significant P value <0.001 and VAS for the rate of pain & satisfaction that ranged from (8.0 ± 0.9) as well as series of photos taken before and after the procedure. No long-term complications were noted however patients complained of annoying pain during the session as well as crust formation that lasted up to 5 days after surgery. In the present study, we introduce the effectiveness of ablative fractional 10,600 nm CO2 laser for treatment of postoperative cleft lip scar after secondary surgical cleft repair rather than ablative CO2 due to its reported complications such as postoperative infection, erythema and pigmentary changes along with prolonged downtime healing. In the current study, we chose early laser treatment within the first six months before complete collagen organisation which will be easier to manage the older scars. Patients mostly complained about the pain during the session as well as dark-coloured crust formation post session that stayed from 3-5 days however they all observed a massive improvement of their scars following treatment protocol.CONCLUSION: Facial wounds sutured in layers heal in a good manner. Patients prefer early treatment with a fractional CO2 ablative laser for postoperative surgical scars. The use of a CO2 fractional laser is safe and effective also causes high patients satisfaction

Formation of protein corona in vivo affects drug release from temperature-sensitive liposomes

Thermally triggered drug release from temperature-sensitive liposomes (TSL) holds great promise for cancer therapy. Different types of TSL have been designed recently for heat triggered drug release inside tumor blood vessels or after accumulation into the tumor interstitium. However, justification of drug release profiles is for far mainly based on in vitro release data. While these methods could be good enough to give early indication about the thermal sensitivity of TSL, they are still far from being optimum. This is because these methods do not take into consideration the actual adsorption of proteins onto the surface of TSL after their in vivo administration, also known as “protein corona” and the influence this could have on drug release. Therefore, in this study we compared thermal triggered drug release profile of two different types of doxorubicin encapsulated TSL; namely the lysolipid-containing TSL (LTSL) and traditional TSL (TTSL) after their in vivo recovery from the blood circulation of CD-1 mice. Ex vivo release profile at 42 °C was then tested either in the presence of full plasma or after removal of unbound plasma proteins (i.e. protein corona coated TSL). Our data showed that the influence of the environment on drug release profile was very much dependent on the type of TSL. LTSL release profile was consistently characterized by ultrafast drug release independent on the conditions tested. On the contrary, TTSL release profile changed significantly. Doxorubicin release from in vivo recovered TTSL was slow and incomplete in the presence of unbound plasma proteins, whereas very rapid drug release was detected from in vivo recovered and purified protein corona-coated TTSL in the absence of unbound proteins. Using mass spectrometry and quantification of protein adsorption, we confirmed that this discrepancy is due to the changes in protein adsorption onto TTSL when heated in the presence of unbound proteins leading to reduction in drug release. In summary this study showed that the formation of the in vivo corona on TSL will have a dramatic impact on their release profile and is dependent on both their lipid composition and the protein content of the environment in which drug release is triggered