Báo cáo khoa học: Hydrogels as Drug Delivery Systems (Hệ dẫn truyền thuốc Hydogels)

SEMINAR REPORT OF 

DRUG DELIVERY SYSTEMS 

Topic: Hydrogels as Drug Delivery Systems 

Reporter: Nguyen Van Tu - 51305919 

Supervisor: 

Dr. Le Thanh Dung 

Dr. Ha Cam Anh 

HCM city, October, 2014

HOOK INTRODUCTION 

Attract 

much 

attention 

Various 

Systems 

to be 

applied 

DDSs 

Hydrogels: 

worth 

concerning 

Each System 

possesses 

particular 

characteristics 

DDSs: Drug Delivery Systems 

2

SOME FIGURES 

The total number of papers on hydrogels from 1950 to 2011 was 43 764. Of 

these, 8554 references were on the topic of drug delivery. In the drug delivery 

topic, the search for subtopics of proteins and genes resulted in 1674 and 284 

references, respectively. 

- S. C. Lee, I. K. Kwon and K. Park, Adv. Drug Delivery Rev., 2013,65,17–20 

3

OUTLINE 

1- GENERALITIES OF GELS AND HYDROGELS – 

FUNDAMENTAL CONCEPTIONS 

2- STRUCTURES OF HYDROGELS – TOWARDS BEING 

USED 

3- THE SYSTHESIS OF HYDROGELS, WAYS TO LOAD 

DRUGS INTO HYDROGELS AND THE RELEASE OF DRUGS 

FROM HYDROGELS 

4- MEANS OF ANALYSIS OF STRUCTURES AND EFFECTIVE 

LOADINGS 

5- POSIBILITIES OF APPLICATION 

6- INCLUSION 

4

I. VIEW OF GELS AND HYDROGELS – FUNDAMENTAL CONCEPTIONS 

1.1. What is gel? 

• Coined by 19th-century Scottish 

Chemist Thomas Graham 

• is a solid, jelly-like material that 

can have properties ranging from 

soft and weak to hard and tough. 

• Gels are defined as a cross-linking 

system, which exhibits no flow 

when in the steady-state. 

• By weight, gels are mostly liquid, yet they behave like 

solids due to a three-dimensional cross-linked network 

within the liquid. 

http://en.wikipedia.org/wiki/Gel 

5


1.1. What is gel? 

• The solid is the continuous phase and the liquid is 

the discontinuous phase. 


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1.2. What is hydrogel? 

• Is a Gel in which the swelling agent 

is water (water is discontinuous 

phase). 

• The network component of a 

hydrogel is usually a polymer 

network. 

• A hydrogel in which 

the network component is a colloidal 

network may be referred to as 

an Aquagel. 


http://www.gcsescience.com/o70.htm 

7



• A hydrogel is an example of 

a smart material. 

• It can change structure in 

response to salt 

concentration, pH and 

temperature. 


http://www.gcsescience.com/o70.htm 

8



• Hydrogels are 3D hydrophilic macromolecular networks 

(matrices) that are capable of retaining a large amount of 

water. 

• Having been used in a variety of applications, such as wound 

dressings, transdermal patches, drug delivery devices, contact 

lenses, or in reconstructive surgery. 

Repeating unit of LBG, Xanth, and a photograph of the obtained physical gel. 

- European Biophysics Journal 2007. Vol: 36(7):693-700. DOI: 10.1007/s00249-007-0158-y 

- Expert Rev Med Devices. 4(2), 147-164 (2007). DOI: 10.1586/17434440.4.2.147 

9


1.3. Major definitions 

• Cross-link 

- A cross-link is a bond that links one polymer chain to 

another. They can be covalent bonds or ionic bonds… 

"Polymer chains" can refer to synthetic polymers or 

natural polymers . 

Cross-links 

- http://en.wikipedia.org/wiki/Cross-link 

Vulcanization with sulfur 

10



• Swelling and deswelling 

11



• Swelling and deswelling 

- Journal of Biomaterials and Nanobiotechnology. 2012, 3, 185-199 

12


1.4. Hydrogels classification 

Classification Contents Classification Contents 

Origin 

- Natural 

- Synthetic 

Cross-linking 

method 

- Chemical (or covalent) 

- Physical (or noncovalent) 

Ionic charge (based 

on the nature of the 

pendent groups) 

- Neutral 

- Anionic 

- Cationic 

- Ampholytic 

Component (based 

on the method of 

preparation) 

- Homopolymer 

- Copolymer 

- Multipolymer 

- Interpenetrating 

Water content of 

degree of swelling 

- Low swelling 

- Medium 

swelling 

- High swelling 

- Superabsorbent 

Function (based on 

the organization of 

the monomers) 

- Biodegradable or 

Nonbiodegradable 

- Stimuli responsive 

- Superabsorbent 

Network Structure 

(porosity) 

- Nonporous 

- Microporous 

- Macroporous 

- Superporous 

Mechanism 

controlling the 

drug release 

- Diffusion 

- Swelling 

- Chemically controlled 

- Environment responsive 


13

II. STRUCTURES OF HYDROGELS – TOWARDS BEING USED 

2.1. Structures 

• Hydrogels are cross-linked polymers that 

have hydrophillic groups (-OH, -COOH, -CONH 2 , 

- SO 3 H, etc). 

Absence of Na + ion 

(remove all salts) 

- http://www.gcsescience.com/o70.htm 

14



Water molecules are 

attracted to the negative 

charges by hydrogen 

bonding 

- http://www.gcsescience.com/o70.htm 

15



-, Journal of Microelectromechanical Systems. Vol.11, No.5, October 2002 

16



- Hydrophilic domains are present, which 

are hydrated in a aquaous environment, 

creating the hydrogel structure. 

- Crosslinks prevent complete mixing of the polymer 

chains and the aquaous phase by providing an elastic 

restoring force that counters the expansion of the 

network. 

- Journal of Microelectromechanical Systems. Vol.11, No.5, October 2002 


17


2.2. Properties to orient to applications 

Biocompatibility 

Biodegradability 

Requirements 

Tunable charateristics 

Balance between mechanical 

and degradation properties 

- Advanced Drug Delivery Reviews, 11 (1993) 59-84 


Adaptability to commonly used 

sterilization procedures 

(implantable systems) 

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* Biocompatibility 

- Hydrogels resemble natural living tissue more 

than any other class of synthetic biomaterials due to 

their high water content and soft consistency which 

is similar to natural tissue. 

- Hydrogels are polymeric materials that do not 

dissolve in water in physiological conditions. 

- Anti toxicity. 

- Advanced Drug Delivery Reviews, 11 (1993) 59-84. 

- Journal of Biomaterials and Nanobiotechnology. 2012, 3, 185-19.9 

- Journal of Materials Chemistry B, 2014, 2, 147-166. 

19



** Biodegradability 

- The degradation processes leading to the 

formation of subspecies should take place 

without any side effects. 

- The removal of the anticipated by-products 

from the body should be given consideration 

before the actual formulation of these systems. 

-The degradation products can be removed by 

excretory pathways. 



20



*** Tunable characteristics 

- Tunable network structure to control the diffusion 

of drugs and tunable affinity for drugs. 

- Invironment responsive hydrogels for release 

drugs (pH, temperature, light, glucose, antigen, 

ionic strength, etc). 



21

III. THE SYSTHESIS OF HYDROGELS, THE WAYS TO LOAD DRUGS INTO 

HYDROGELS AND THE RELEASE OF DRUGS FROM HYDROGELS 

3.1. Preparations of hydrogels 

Hydrogels 

Natural 

hydrogels 

Natural 

polymers 

Synthetic 

hydrogels 

Synthetic 

polymers 

Cross-linking 

physical bonds 

Cross-linking 

chemical bonds 

Cross-linking 

polymerization 

of Synthetic 

Monomers 


- Progress in Polymer Science. Vol 32, No.7, 2007, pp.669–697 

22




• Especially, 

Natural hydrogels 

Synthetic hydrogels 

Hydrogels with 

particular properties 

- Advanced Drug Delivery Reviews, Vol. 11, No. 1-2, 1993, pp. 59-84 

- Syed K. H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips. Hydrogels: Methods of Preparation, 

Characterisation and Applications. 2011, InTechOpen. 

23




3.1.1. Physical cross-linking 

Hydrogels obtained are called physical gels or 

reversible gels 

Properties 

Easy to production 

The advantage of not using cross-linking agents 



24





Heating/cooling a polymer solution 

Ionic interaction 

Means 

Complex coacervation 

H-bonding 

Maturation (heat induced aggregation) 

Freeze-thawing 



25





CMC 

H-bonding 

- Transactions of the Materials Research Society of Japan, Vol 32, No 332, 713-716 

26





- H-bonded hydrogel can be obtained by lowering the pH of 

aqueous solution of polymers carrying carboxyl groups. 

- Examples of such hydrogel is a hydrogen-bound CMC 

(carboxymethyl cellulose) network formed by dispersing CMC 

into 0.1M HCl. 

- The mechanism involves replacing the sodium in CMC with 

hydrogen in the acid solution to promote hydrogen bonding. 

- The hydrogenbonds induce a decrease of CMC solubility in 

water and result in the formation of an elastic hydrogel. 

- Transactions of the Materials Research Society of Japan, Vol 32, No 332, 713-716 

27




3.1.2. Chemical cross-linking 

Grafting of monomers on the backbone of the 

polymers or 

Properties 

The use of a cross-linking agent to link two polymer chains 

The cross-linking of natural and synthetic polymers can 

be achieved through the reaction of their functional 

groups 



28





Using chemical cross-linkers 

Methods 

Grafting monomers on 

preformed polymer 

Radiation cross-linking 



29





For example: preparation of Carageenan/GA hydrogels 

- Glutaraldehyde (GA) with a certain concentration (1-5 wt%) 

was prepared by diluting GA 25 wt% GA solution) with distilled 

water. The carrageenan film was immersed in GA-water mixture 

for 2 min. 

- The surface of film was wiped with filter cloth and then cured at 

110 0 C in oven for 25 min. The crosslinked film was soaked in 

water with stirring for 1 min and then in ethanol for 4 hr to 

remove unreacted GA. The wet hydrogels were dried at room 

temperature to a constant weight. 

- Engineering Journal, Volume 17, Issue 3, 2013, ISSN 0125-8281. DOI:10.4186/ej.2013.17.3.57 

30





For example: preparation of Carageenan/GA hydrogels 

- Engineering Journal, Volume 17, Issue 3, 2013, ISSN 0125-8281. DOI:10.4186/ej.2013.17.3.57 

31



3.2. Preparation of drug-loaded hydrogels 

The samples of hydrogels were immersed in 

a solution of drugs. 

General 

methods 

The swollen hydrogels loaded with drug were placed 

in a vacuum oven and dried under vacuum at 

certain temperature. 

The loading amount of drug in the hydrogels was 

specified from the decrease in the concentration of 

drug solution using UV spectrophotometer. 

The loading efficiency of hydrogels was calculated as 

the ratio of the final to the initial drug concentration 

32




• Powdered samples of Pc-poly(NaAAco-AAm), 

hydrogel (1 g ± 0.0001), 

were accurately weighted and 

immersed in an alkaline solution of 

ibuprofen (IBU, 0.54 g dissolved in 50 

mL distilled water) at 0˚C for 25 h. 

• The swollen hydrogels loaded with 

drug were placed in a vacuum oven and 

dried under vacuum at 37˚C. 

Ibuprofen (IBU) 

• Mohammad Sadeghi 

- Journal of Biomaterials and Nanobiotechnology, 2011, 2, 36-40. DOI:10.4236/jbnb.2011.21005 

33




• The loading amount of drug in the 

hydrogels was calculated from the 

decrease in the concentration of the 

IBU solution which was determined 

using a UV spectrophotometer. 

• The loading efficiency of the Pectinbased 

hydrogels was calculated as the 

ratio of the final to the initial IBU 

concentration. 




34







35




• PEC/PAM and PEC/DEAMA hydrogels 

- drug conjugate was prepared by 

desolving different weights of drug 

(Chlortetracycline HCL as model drugs) 

(0.2, 0.3, 0.35, 0.4 and 0.5 mg) each in 

distilled water to prepare (0.2, 0.3, 0.35, 

0.4 and 0.5 mg/ml) drug concentrations. 

Chlorotetracycline 

(CTC) - Antibiotic 

• Faten I. Abou El Fadl 

and Nabila A. Maziad 

- J Radioanal Nucl Chem . DOI 10.1007/s10967-014-3514-2 

36




• The dry polymer blends with known 

weight 0.1 g), were soaked into the 

drug solutions at room temperature 

until the complete adsorption for 72 h. 

• Then the amount of drug adsorbed 

onto polymer hydrogels at different 

compositions was determined by 

using UV–Vis spectrophotometer at 

identical drug absorbance wavelength. 

Chlorotetracycline 

(CTC) - Antibiotic 

• Faten I. Abou El Fadl 

and Nabila A. Maziad 


37

III. THE SYSTHESIS OF HYDROGELS, WAYS TO LOAD DRUGS INTO 

HYDROGELS AND RELEASE DRUGS 

3.3. Release drug from hydrogels 

3.1. Mechanism 

• The mechanism of drug release consists of the 

following phenomena: 

1- Exterior diffusion, 

2- Interior diffusion, 

3- Desorption, 

4- Chemical reactions, 

5- Matrix erosion. 

- Roman ZARZYCKI, Zofia MODRZEJEWSKA and Katarzyna NAWROTEK. 

Ecological Chemistry and Engineering, Vol.17, No.2, 2010. 

38




3.1. Mechanism 

• The release of water-soluble drug, entrapped in a 

hydrogels, occur only after water penetrates the network to 

swell the polymer and dissolve the drug, followed by 

diffusion along the aqueous pathways to the surface of the 

device. 

• The release of drug is closely related to the swelling 

characteristics of the hydrogels, which in turn, is a key 

function of chemical architecture of the hydrogels. 

- J Mater Sci: Mater Med (2008) 19:2771–2780. DOI 10.1007/s10856-008-3406-5 

39




3.2. Experiments 

Placing dried and loaded sample in definite 

volume of different pH medium at 37 0 C. 

At specific time intervals, certain aliquots of 

sample was withdrawn and determined by UV 

spectrophotometer. 

Released drug (%) = R t /L x 100 

- J Mater Sci: Mater Med (2008) 19:2771–2780. DOI 10.1007/s10856-008-3406-5. 



40





Baljit Singh, Ritu Bala and Nirmala Chauhan 

• Tetracycline hydrochloride-loaded Psy-cl-poly(AAc) 

hydrogels were immersed in different pH buffer 

including distilled water, pH 2.2 and pH 7.4. 

• After 30 min, aliquots were got and measured 

spectrophotometrically at λ max = 357, 358 and 362 nm. 


41





• At higher pH, amount of released drug was higher and 

quicker. 


42





• Faten I. Abou El Fadl and Nabila A. Maziad 

- J Radioanal Nucl Chem . DOI 10.1007/s10967-014-3514-2. 

43




3.3. Various environmental stimuli for triggering drug release from 

reponsive hydrogels 

- Journal of Biomaterials and Nanobiotechnology, 2012, 3, 185-199 . DOI:10.4236/jbnb.2012.32025 

44




3.3. Various environmental stimuli for triggering drug release from 

reponsive hydrogels 


45

IV. MEANS OF ANALYSIS OF STRUCTURES AND EFFECTIVE LOADINGS 

4.1. Analysis of structures and characteristics 

• There are a number of methods of analysis of 

hydrogels structure which depends on the preparation, 

aims to define charaterization parameters. 

• Susana Simões, Ana Figueiras, and Francisco Veiga 

summaried all of techniques of measurement, as table 

below: 


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47




48


4.2. Focussing on analysis of structures 

Swelling study 

Analysis of 

Structure 

IR Spectroscopic analysis 

Ultraviolet (UV) analysis 

Thermogravimetric analysis 

(TGA) 

49



4.2.1. Swelling studies 

Target 

- Calculate 

percentage of the 

total water uptake 

Define some 

coefficients for 

measuring 

swelling kinetics 



50



4.2.2. IR Spectroscopic analysis 

Purpose 

Specify functional 

groups at specific 

wavenumbers 

Confirm the 

interaction 

between polymers 

in hydrogels 




51



4.2.2. IR Spectroscopic analysis 

The appearance of new peaks indicates the stretching of some 

functional groups when creating hydrogels. 


52



4.2.3. Ultravillet (UV) analysis 

Goals 

Determining the amount of 

drug adsorbed onto hydrogels 

(effective adsorption) 

Specifying the quantity of 

drug released from hydrogels 

in different media 




53



4.2.3. Ultravillet (UV) analysis 

- N.A. Peppas et al. / Journal of Controlled Release, 62 (1999) 81–87 

54



4.2.4. Thermogravimetric analysis (TGA) 

Objectives 

Studying thermostability of 

hydrogels 

Measuring the compositions of 

hydrogels 


55



4.2.4. Thermogravimetric analysis (TGA) 


56

V. POSIBILITIES OF APPLICATION 

5.1. View of applications 

• In recent years, there has been remarkable process in the 

development of clinically applied hydrogels. 

• Since 1960, the copolymers of 2-(HEMA) and ethylene 

dimethacrylate have been applied for their use in contact 

lens, urinary catheters, wound dressing and surgical 

gloves, etc. 

• After that, development of clinically applied hydrogels 

has attracted research regards. 


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58




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5.2. Some of specific applications 

• Implanting degradable insulin loaded-poly(NIPAAmco-Dex-lactateHEMA) 

hydrogels to rat’s conjunctiva 

for treating diabetic retinopathy. 

- G.P. Misra et al. / Biomaterials 30 (2009) 6541–6547 

60



• Results of research demonstrated that both hydrogels and 

their degradation products were non-toxic to cultured R28 

retinal cells, and accordingly the hydrogels have potential for 

in vivo implantation. 

• None of inflammation or morphological changes in eyes 

implanted insulin loaded hydrogels. 

- G.P. Misra et al. / Biomaterials 30 (2009) 6541–6547 

61



• Investigating starPEG-heparin-based hydrogels 

loaded by some Growth Factors (GFs): bFGF and 

EGF. 

• Applying to treat acute kidney injury on mice. 

• The results confirm possitive indication to ultilizing 

hydrogels for GFs delivery. 

- M.V. Tsurkan et al. / Journal of Controlled Release 167 (2013) 248–255 

62




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• No visual signs of inflammation for both the control 

and the GFs treated mice. 

• The hydrogels alone did not induce treatment 

efficency. 

• There was the difference of proliferation between the 

left injected GF and the right non-injected GF kidney. 


64


5.3. Some drawbacks of hydrogels in DDSs 

May release toxic subtances 

Hydrogels 

Low mechanical strength 

->limits load bearing 

Moist -> sterility, shipping, packing 

Some risks of infection, delayed wound 

healing. 


65

VI. SUMMARY 

• Hydrogels are considered one of drug delivery 

systems which has crucial position in medical 

applications. 

• There has been a great number of researches 

related to hydrogels, which aims to apply to target 

diseases on the majority of human body. 

• Besides advantages, hydrogels also have some 

drawbacks requiring the advance of design of 

hydrogels’ properties. 

66

Good day 

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Báo cáo khoa học: Hydrogels as Drug Delivery Systems (Hệ dẫn truyền thuốc Hydogels)

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