Geri Dön

İlaç yüklü pH duyarlı poliüretan filmlerin sentezi ve karakterizasyonu

Synthesis and characterization of drug loaded ph sensitive polyurethane films

PDF İndir

  1. Tez No: 577893
  2. Yazar: FULYA GÜLMEZ
  3. Danışmanlar: PROF. DR. FATMA SENİHA GÜNER
  4. Tez Türü: Yüksek Lisans
  5. Konular: Kimya Mühendisliği, Chemical Engineering
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2019
  8. Dil: Türkçe
  9. Üniversite: İstanbul Teknik Üniversitesi
  10. Enstitü: Fen Bilimleri Enstitüsü
  11. Ana Bilim Dalı: Kimya Mühendisliği Ana Bilim Dalı
  12. Bilim Dalı: Kimya Mühendisliği Bilim Dalı
  13. Sayfa Sayısı: 81

Özet

Polimerik malzemeler, yapısal özelliklerinden dolayı biyomalzeme olarak yaygın kullanıma sahiptirler. Bunlardan poliüretanlar; düşük toksisite, mükemmel kimyasal ve mekanik özelliklerinden dolayı önemli olup protez, implant ve kontrollü ilaç salım sistemlerinde ve daha birçok alanda yaygın olarak kullanılmaktadır. Bu çalışmada, ilaç taşıyıcı sistem olarak kullanılmak üzere poliüretan (PU) filmler sentezlenmiştir. İlaç olarak amino-ester gruplarına sahip bir lokal anestezik olan prokain hidroklorür seçilmiştir. Tek adım kütle polimerizasyonu yöntemiyle farklı formülasyonlarda poliüretan filmler, poliol olarak polietilen glikol (PEG), izosiyanat kaynağı olarak hekzametilen diizosiyanat (HDI), çapraz bağlayıcı kaynağı olarak hint yağı (HY) kullanılarak sentezlenmiştir. Sentezlerde 1, 4-bütandiol (BDO) zincir uzatıcı olarak kullanılmıştır. Sentezlenen poliüretan filmler Fourier dönüşümlü kızılötesi (FT-IR) spektroskopisi, diferansiyel taramalı kalorimetresi (DSC ve taramalı elektron mikroskopisi (SEM) yöntemleriyle karakterize edilmiş, ayrıca şişme deneyleri yapılmıştır. Çalışmada, negatif sıcaklık ve pH duyarlı poliüretan malzemeler sentezlenmiştir. Farklı molekül ağırlıklarında (3000 ve 1500 g mol-1 ) ve farklı HY/PEG oranlarında (80/20, 70/30, 50/50) sentezlenen poliüretanların ilaç yükleme ve salım davranışları UV-spektroskopisi kullanılarak incelenmiştir. İlaç salım ortamı olarak yara örtüsü (pH 6.4 ve 5.8) ve mide (pH 2.3) ortamını taklit edecek biyolojik tampon çözeltileri kullanılmıştır. Elde edilen verilere göre, poliüretan sentezinde kullanılan PEG'in molekül ağırlığının azalmasının ilaç salımının artmasına neden olduğu belirlenmiştir. Ayrıca ortam pH'sındaki değişmelerin poliüretan matriksin ilaç salım performansına etki ettiği de gösterilmiştir. İlaç salım miktarı pH 2.3'de yüksek (% 100) iken pH 6.4'te daha düşük (%31 ) değerlerde olmaktadır. İlaç salımı yüksek pH değerlerinde (pH 6.4 ve 5.8) şişme mekanizması, düşük pH değerinde ise (pH 2.3) iki kademeli olarak hem şişme hem de PEG zincirlerinin kopması sonucu gerçekleşen polimer degradasyonu ile kontrol edilmektedir.

Özet (Çeviri)

Polymer based materials have a wide range of applications in the biomedical field due to their desired properties. Polyurethane (PU) is one of the most important group of polymer, used in prosthetic, implant, controlled drug delivery systems, since it has low toxicity due to its excellent chemical and mechanical properties. Polyurethanes are formed by reacting isocyanates and high molecular weight polyols in order to obtain polymers with urethane bonds (–NH–COO–) in the main chain. It is known that polyurethanes made from aliphatic diisocyanates are more resistant to ultraviolet irradiation, while aromatic diisocyanate-based polyurethanes can undergo photodegradation. It has been also previously reported that polyurethanes synthesized from aliphatic isocyanates are more biocompatible than aromatic isocyanate-based polyurethanes. Due to the fact that aromatic- based polyurethanes may degrade to yield carcinogenic aromatic amines, it is avoided for biological applications. Therefore, aliphatic PU was preferred in the current study. Isocyanates and polyols are usually coupled with other diols or diamines which work as the chain extenders. Depending on the diols or isocyanates used, it is possible to control the mechanical and physical properties of the polurethanes. Structure of the polymer contains both soft and hard segments. Hard segments mostly consist of isocyanates having and diol or diamine, all having low molecular weight. It is known that the hard segment is semicrystalline and has a high glass transition temperature compared to the soft segments which are mostly composed of diols of long chain molecules providing the flexibility. It is important to assign the isocyanate and chain extender to be used in the polymerization process since they strongly influence the physical properties of the polyurethane. Thus, if the ratio of these hard and soft segments is arranged, desired chemical and mechanical properties can be sustained with their hydrophobic or hydrophilic properties, softness or hardness. In this study, usage of polyurethanes in controlled release of drugs, which is one of the most common biomedical applications for degradable polyurethanes, was investigated. By reacting all reactants in one step bulk polymerization, polyurethane films were synthesized. Polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), castor oil (CO) were used as polyol, isocyanate and cross linker source, respectively. Chain extender, 1, 4-butanediol (BDO), was used in the PU synthesis . HDI and BDO are the hard segments, and PEG is the soft segment of PU.The hard segment of the resulting PU consists of HDI, while PEG generates the soft segment. It is reported that PEG, which is a hydrophilic segment as it is highly soluble in water and organic solvents, has been preferred for many biomedical applications. It is nonimmunogenic and it has non-toxic degradation products while low molecular weight PEG can be excreted via the kidney while not causing any biological problem. In recent studies it is also found that monitoring the hydrophilic/hydrophobic balance of polyurethanes could cause temperature-sensitivity, which makes it potential material for controlled drug delivery. Additionally, having lower cost and toxicity, and being an alternative to hydrocarbon-based raw materials as a renewable agricultural resource, make vegetable oil-based polyols including CO to be preferred for the preparation of PUs. Furthermore, CO demonstrated good compatibility with polyethylene glycol which may result in improving properties while producing PU elastomers. Therefore CO, a fatty acid containing hydroxyl group as a main component, was used as raw material in the synthesis. Procaine hydrochloride, a local anesthetic with amino-ester groups, was chosen as the model drug in the study. Polyurethane films were characterized by Fourier Transform Infrared Spectrophometry (FT-IR), Differantial Scanning Calorimetry (DSC) and Scanning Eletron Microscopy (SEM) methods, and swelling studies were performed. Drug loading and release behaviors of polyurethanes, having different molecular weights and CO / PEG ratios, were investigated by using UV-spectroscopy. Samples were named using the abbreviation PU-x-y, in which x represents the molecular weight of PEG and y stands for the weight ratio of CO to PEG. In the present study, four PU films having different formulations were synthesized by bulk polymerization. Different CO/PEG weight ratios of 50/50, 70/30, 80/20 with PEG having 1500 and 3000 g mol-1 were examined.In the beginning of the polymerization reaction of PU 3000-70, the peaks belonging to hydroxyl groups at around 3428 cm–1 and the free isocyanate peak at around 2261 cm–1 were observed. At the end of the reaction, the peak of free isocyanate was disappeared and characteristic urethane peak was observed at around 3320 cm–1 for all polyurethanes.The band at around 2261cm-1, associated to the isocyanate groups, was not observed in any sample, which means that the polymerization proceeded quantitatively. According to obtained results, It was demostrated that increasing in ratio of CO, the cross linker, to PEG as polyol source in the polyurethane synthesis caused detention in the drug release. Furthermore, the decrease in the molecular weight (Mw) of the PEG used in the films during the synthesis, caused an increase in the drug release. Data obtained from DSC shows that the Tg and Tm of the polyurethanes mainly depends on the molecular weight of PEG and content of CO in polyurethanes. Water absorption and swelling are significant factors to design a drug delivery system. It is known that swelling behavior relies upon the composition of the polymer and the temperature of the external solution. Polyurethanes may show significant polymer swelling that effect the drug release kinetics, controlled by the polyol used. Drug loading studies were performed at pH 9.1, 25° C and 150 rpm. Drug release experiments were conducted at three different pH values (2.3, 5.8, 6.4), 32° C and 200 rpm. The amount of drug release in the acidic medium reached to 100%, showing that the synthesized polyurethane film is pH sensitive and maximum release is seen in pH 2.3 among all the mediums. The drug relase was dominated by swelling mechanism at higher pH values, whereas at pH 2.3 the release which had two stage patterns was controlled by both swelling and degradation of polyurethane films. Hydrophilic segments of polyurethane film cause the rapidly acidic hydrolytic degradation. Oxygen atoms of ether chain in PEG get protonated and the soft segment interacts more with water, enhancing the soft segment solubility and hydrolytically degradation at low pH. In addition the drug release experiments, overloaded drug studies were done. The purpose of overloaded drug study is to observe if drug could diffuse out in case the driving force is increased by increasing the drug concentration however, it is discovered that, all the films with drug overloading show low drug release amounts. This is resolved by the fact that drug molecules cannot come out because of the diffusion pathways being closed with drug molecules. Moreover, low amount of drug release even in extreme conditions at pH 6.4 proves that the polyurethane film is pH responsive since it releases the drug more at acidic pH of 2.3. Overall, the pH and negative temperature sensitive drug loaded polyurethane films have been successfully synthesized. It is determined that the films are and potential candidates to be used as procaine hydrochloride delivery vehicles for both stomach and wound treatments. In addition, it is concluded that the formulation of matrix, amount and conditions of drug loading and pH of the release media have significant impact on the drug release.

Benzer Tezler

  1. Tez No

    837060

    5-fluorourasil için polimer/biyoseramik ve grafen oksit içerikli ilaç taşıyıcı malzeme üretimi ve kinetik çalışmaları

    Production and kinetic studies of polymer/bioceramic and graphene oxide containing drug carrier materials for 5-fluorouracil

    EBRU KAHRAMAN

    Doktora

    Türkçe

    Türkçe

    2023

    Kimya Mühendisliğiİstanbul Teknik Üniversitesi

    Kimya Mühendisliği Ana Bilim Dalı

    PROF. DR. GÜLHAYAT SAYGILI

  2. Tez No

    855740

    Synthesis of drug loaded pH sensitive albumin nanoparticles

    İlaç yüklü pH duyarlı albümin nanoparçacıkların sentezi

    EDA ARGITEKİN

    Yüksek Lisans

    İngilizce

    İngilizce

    2023

    Mühendislik Bilimleriİzmir Yüksek Teknoloji Enstitüsü

    Malzeme Bilimi ve Mühendisliği Ana Bilim Dalı

    PROF. DR. YAŞAR AKDOĞAN

    DOÇ. DR. UMUT ADEM

  3. Tez No

    70287

    pH-Duyarlı monolitik sistemlerden diklofenak sodyumun kontrollu salımı

    Sustained release of diclofenac sodium from pH-sensitive monolithic systems

    HASAN BASAN

    Yüksek Lisans

    Türkçe

    Türkçe

    1998

    Eczacılık ve FarmakolojiGazi Üniversitesi

    Analitik Kimya Ana Bilim Dalı

    PROF. DR. M. TEVFİK ORBEY

  4. Tez No

    338567

    pH responsive nano carriers for anti cancer drug delivery

    pH duyarlı anti kanser ilac taşıyıcı nanosistemler

    SHAHLA BAGHERIFAM

    Doktora

    İngilizce

    İngilizce

    2013

    BiyoteknolojiOrta Doğu Teknik Üniversitesi

    Polimer Bilim ve Teknolojisi Ana Bilim Dalı

    PROF. DR. NESRİN HASIRCI

    PROF. DR. VASIF NEJAT HASIRCI

  5. Tez No

    536716

    Hedeflendirilmiş antikanser ilaç yüklü polimerik nanotaşıyıcıların formülasyonları ve karakterizasyonları

    Formulation and characterization of anticancer drug loaded targeted polymeric nanocarriers

    NAİLE ÖZTÜRK

    Doktora

    Türkçe

    Türkçe

    2019

    Eczacılık ve FarmakolojiHacettepe Üniversitesi

    Farmasötik Teknoloji Ana Bilim Dalı

    PROF. DR. İMRAN VURAL

Geri Dön