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Home > Solid Lipid Nanoparticles for Thermoresponsive Drug Delivery: Fabrication and Evaluation

Solid Lipid Nanoparticles for Thermoresponsive Drug Delivery: Fabrication and Evaluation

Thesis Info

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Author

Rehman, Mubashar

Program

PhD

Institute

The Islamia University of Bahawalpur

City

Bahawalpur

Province

Punjab

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Pharmaceutics

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13712/1/Mubashar_Rehman_Pharmaceutics_HSR_2017_IUB_Bahawalpur_03.08.2018.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727184456

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Thermoresponsive drug delivery systems (DDS) are designed for the controlled and targeted release of therapeutic payload by exploiting the hyperthermic temperature (>39°C), which may be applied by some external means or an encountered symptom in inflammatory diseases such as cancer, arthritis etc. However, available thermoresponsive DDS, including liposomes, have complex method of preparation involving toxic solvents and reagents. Recently, we have shown for the first time that melting point of solid lipid nanoparticles (SLN) can be optimized for thermoresponsive drug release by tuning their melting point (MP). The objective of this study was to provide some strong evidence in support of hypothesis that thermoresponsive solid lipid nanoparticles (TSLN) undergo solid-liquid phase transition at their melting point (>39ºC) leading to faster drug release. Thermoresponsive lipid mixtures (TLM) were prepared by mixing solid (lauric, myristic, palmitic and stearic acid) and liquid (oleic and linoleic acid) natural fatty acids in different ratios (0.1:1 to 1:2) and melting point was measured by differential scanning calorimetry (DSC). A graph was plotted between liquid content in TLM and the MP, and TLM that would melt at 39°C were identified by using straight line equation of the graph. The solidliquid phase transition was assessed by determination of temperature dependent change in viscosity (low at 39°C) and light transmission (higher at 39°C) that are characteristic of liquids. TSLN containing a chemotherapeutic drug, either hydrophilic 5-fluorouracil (5-FU) or lipophilic paclitaxel, were synthesized by hot melt encapsulation method. It should be noted that the TLM and the TSLN were made by physical interaction of materials and no chemical reaction was needed. The TSLN showed desirable spherical shape (TEM), size (100-300 nm), physicochemical stability (FTIR analysis), high yield (>85%) and encapsulation efficinecy (5-FU >40% and paclitaxel >90%). In 5-FU loaded TSLN, drug release studies were first performed by USP type II dissolution apparatus in PBS (7.4) at 37°C and 39°C. A sustained release pattern was observed at 37°C and 22-34% 5-FU was released in 5 hrs. On the other hand, >90% drug was released at 39°C suggesting that the SLN show thermoresponsive drug release in agreement with our hypothesis. Drug release from SLN at 39°C was similar to model oleic acid and linoleic acid nanoemulsions which further supports our hypothesis. Next, a quick and real-time differential pulse voltammetry (DPV) based electrochemical chemical detection method was developed using a graphite electrode to detect change in current with 5-FU concentration while increasing voltage was applied on reference and counter electrodes. This method also showed that sustained release pattern of 5-FU at 37°C was converted to an immediate drug release when heated to 39°C, thus, confirming the thermoresponsive drug release. In case of paclitaxel loaded TSLN, drug release was minimum at 37°C and 70-100% drug release achieved after 60 hrs. On the other hand, whole drug was released in 4-7 hours at 39°C. This 15-20 time higher drug release at hyperthermic conditions confirmed the thermoresponsive drug release from the TSLN. Blank SLN were found to be biocompatible with human gingival fibroblast cells (PCS- 201-108) although and breast cancer cells (MDA-MB-231). However, 5-FU loaded SLN showed some cytotoxicity after 24 hours which was due to the release of drug. 5-FU loaded SLN showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (22-28%) compared to 37°C (<10%) within 1 hour. Similarly, paclitaxel loaded TSLN showed higher cytotoxicity to glioblastoma cells at 39°C (31% cell viability after one hour) compared to 37°C (18% cell viability). The higher cytotoxicity at 39°C was due to the higher drug release. Finally, the TSLN were evaluated for brain targeting across blood brain barrier (BBB) and an in vitro BBB model was used consisting astrocytes (CRL-2541) and endothelial cells (b.End3). The BBB model was optimized at 39°C for 1 hour duration due to retention of semipermeable nature and lack of paclitaxel and heat related toxicity. The TSLN showed higher permeability across BBB at 39°C which may be attributed to the deformable liquid state that squeezes through the tight junctions of BBB without any damaging effects. In conclusion, the novel TSLN reported in this thesis may serve as safe and effective platform of thermoresponsive targeting of cancer.
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مولانا احتشام الحسن کاندھلوی

مولانا احتشام الحسن کاندہلوی
افسوس ہے ہمارے عزیز اور فاضل دوست مولانااحتشام الحسن کاندہلوی بھی گزشتہ نومبر میں شدید علالت کے بعد انتقال کرگئے۔مولانا کاندہلہ کے رئیسوں میں شمار ہوتے تھے لیکن ان کا مشغلہ تبلیغی کتابوں کی تصنیف وتالیف اور مطالعہ کے سوا کچھ نہ تھا۔شب وروز اسی میں بسر ہوتے تھے اور گفتگو کاموضوع بھی بس یہی ایک بات ہوتی تھی۔تبلیغی جماعت کے طریق کارسے ان کو اختلاف تھا۔وہ کہا کرتے تھے کہ تبلیغ تو نام ہی اسلام کوغیر مسلموں تک پہنچانے کا ہے۔ مرض الوفات میں مبتلاہونے سے ایک ماہ قبل علی گڑھ آئے اور ایک ہفتہ کے قریب قیام کیا۔ان دنوں میں ان سے کئی مرتبہ ملاقات ہوئی اورہرملاقات میں وہ اپنے اس محبوب موضوع پرتقریر کرتے رہے ہیں۔میں حسب عادت خاموش سنتا رہا اور بولا کچھ نہیں۔مرض الوفات میں انھوں نے بڑی سخت تکلیف اٹھائی لیکن صبر ورضا کادامن ہاتھ سے نہیں چھوڑا۔ بڑے خلیق اورعابد وزاہد بزرگ تھے۔اﷲ تعالیٰ ابرار وصلحا کامقام عطا فرمائے آمین۔ [جنوری ۱۹۷۲ء]

 

Sir Syed Ahmad Khan and his Historical Writings (Notes)

Sir Syed Ahmad Khan was interested in history and history-writing. His areas of interest were Islamic and South Asian history. In this essay, we examine certain relevant facets of this interest and its manifestation. There are a vast number of studies on the life, achievements and goals of Sir Syed Ahmad Khan [1817-1898]. His essays have been collected from his journalism in 18 volumes by Muhammad Ismail Panipati1 and his other writings, lectures and letters have also received editorial attention. A useful tool in this regard is the compilation titled Kitabiyat-i-Sir Syed made by Ziauddin Lahori.2 As this paper focuses on Sir Syed’s historical writings, we may mention here a recent doctoral thesis of Syeda Jabin Zehra on this very topic.3 As a matter of fact, any and all of Sir Syed’s writings be they on education or religion now come under the ambit of history but our narrower focus will be on those writings that deal with history as history alone though they may also admit of other classifications.

Proportional Load Sharing and Stability of Dc Microgrid

AC electrical distribution system is presently dominating whose engineering foundations were planned above hundred years ago. However, the debate between ac and dc distribution system has started again due to the evolution of dc loads and increasing use of renewable energy sources (RESs). Currently, depleting threat of conventional fuels, growing energy demand and prices, and ecological changes necessitate that considerable power to be produced through RESs. Microgrids are modern form of distribution system which can function autonomously or in combination with main supply grid. Microgrids can operate in low or medium voltage range which have their own power generation with energy storage and loads. The unique property of the microgrids is that they can work in islanded mode under faulty grid conditions which increases the reliability of power supply. This inspires that microgrid is an e ective way of power generation and consumption. In the near future, the distribution system may consist of some interconnected microgrids with local generation, storage and consumption of power. Solar, wind and fuel cell technologies are playing an important role in electric power generation among various renewable sources. Most of these sources are inherently designed for dc or they are dc friendly. The growing use of these sources and fast evolution of domestic appliances from ac to dc attracting dc microgrids in the distribution system. DC microgrid system may be more e cient compared to the ac system because the integration of RESs in dc requires less conversion stages compared to ac. Additionally, the reactive power compensation and frequency synchronization circuits are not required in dc microgrids. DC microgrids are not exempted from the stability concerns. In therst part of this thesis, voltage stability of dc microgrid based on decentralized control architecture is presented. Droop controllers are being used for voltage stability of dc microgrids. But droop control is not e ective due to the error in steady state voltages and load power variations. Further, the voltage deviation increases with the increase in droop values which are not acceptable to the loads. Additionally, proportional integral (PI) controllers are being used to realize droop control for the ix stability of dc microgrid. The main reason to use these control techniques is due to easy implementation of their tuning method in industrial applications. However, PI controllers cannot ensure global stability. They exhibit slower transient response and control parameters cannot be optimized with load power variations. To address the aforementioned limitation, sliding mode control (SMC) is proposed for voltage stability of dc microgrid in this thesis. Main advantages of SMC are high robustness, fast dynamic response and good stability for large load variations. To analyze the stability and dynamic performance, mathematical model of a dc microgrid is derived. Controllability and stability of the modeled system are veri ed. Hitting, existence and stability conditions are veri ed through SM. Modeled dynamics of the system are graphically plotted which shows that system trajectories converge to the equilibrium point. Detailed simulations are carried out to show the e ectiveness of SM controller and results are compared with droop controller. SMC showed good voltage regulation performance in steady state condition. The e ect of transient on a step load is also investigated which con rms the good performance of the proposed controller. Further, a small scale practical setup is developed, and results are presented. In the second part of this thesis, distributed architecture using SM controller is proposed for proportional load sharing in dc microgrid. The key objectives of the dc microgrid include proportional load sharing and precise voltage regulation. Droop controllers are based on decentralized control architecture which are not e ective to achieve these objectives simultaneously due to the voltage error and load power variations. Centralized controller can achieve these objectives using high bandwidth communication link. However, it loses reliability due to the single point failure. To address limitations, a distributed architecture using SM controller utilizing low bandwidth communication is proposed in this thesis. Main advantages are high reliability, load power sharing and precise voltage regulation. To analyze the stability and dynamic performance, system model is developed and its transversality, reachability and equivalent control condition are veri ed. Furthermore, the dynamic behavior of the modeled system is investigated for underdamped and critically damped response. Detailed simulation results are carried out to show the e ectiveness of the proposed controller.