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superporus hydrogels
- 2. Three-dimensional networks of hydrophilic polymer chains that do not dissolve but can swell in water both solid like and liquid like properties high biocompatibility environmental stimuli respondent (temperature, pH, light, specific molecules) Ideal for controlled drug delivery
- 3. - various criteria for the classification of hydrogels Origin Natural Synthetic Water content or Low swelling degree of swelling Medium swelling High swelling Superabsorbent Porosity Nonporous Microporous Macroporous Superporous Cross-linking Chemical (covalent bonding) Physical (noncovalent bonding) Biodegradability Biodegradable
- 4. Swelling property is influenced by: •type and composition of monomers •other environmental factors such as : temperature, pH, ionic strength •cross-linking Mechanical strength and permeability Rs = (Ws-Wd) / Wd Rs = swelling ratio Ws = weight of swollen hydrogels Wd = weight of dried hydrogels Cross-linking and/or copolymerization with hydrophobic comonomers density↑, mechanical strength↑, swelling property ↓
- 5. Chemical Physical hydrogels hydrogels Covalently Noncovalently crosslinked crosslinked ▪ Hydrogen bonding ▪ hydrophobic interaction ▪ crystallinity ▪ stereocomplex formation Thermoset Thermoplastic hydrogels ▪ ionic complexation hydrogels Volume phase Sol-gel phase transition transition Reliable shape stability Limited shape stability and memory and memory
- 6. Chemical crosslinking Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent + Copolymerizatio n MonomerCrosslinker or Polymerization Hydrogel network Vinyl group-containing water-soluble polymers
- 7. Physical crosslinking Chemical and Physical crosslinking • Cross-linking without chemical reaction • ionic interaction, hydrogen bonding, antigen-antibody interaction, supramolecular association • Ionic hydrogel
- 8. Monomer abbreviation Monomer HEMA Hydroxyethyl methacrylate HEEMA Hydroxyethoxyethyl methacrylate HDEEMA Hydroxydiethoxyethyl methacrylate MEMA Methoxyethyl methacrylate MEEMA Methoxyethoxyethyl methacrylate MDEEMA Methoxydiethoxyethyl methacrylate EGDMA Ethylene glycol dimethacrylate NVP N-vinyl-2-pyrrolidone NIPAAm N-isopropyl Aam AA Acrylic acid HPMA N-(2-hydroxypropyl) methacrylamide EG Ethylene glycol PEGMA PEG methacrylate
- 9. - Benefits of controlled drug delivery more effective therapies with reduced side effects the maintenance of effective drug concentration levels in the blood patient’s convenience as medicines hence increased patient compliance - Release mechanisms of drug molecules : diffusion, dissolution, osmosis, ion exchange
- 10. - Diffusion controlled Drug Delivery (1) Polymer matrix Water-insoluble Polymer matrices time (2) Reservoir system Water-insoluble Polymer membrane time
- 11. Environment-Sensitive Hydrogels • respond to environmental change : temperature, pH, specific molecule • reversible volume phase transition or sol-gel phase transition • “intelligent” or “smart” hydrogel Drug-loaded gel Change in pH for gel swelling Change in temperature for gel collapse Drug release through Drug release by the the swollen network squeezing action
- 12. Environmental-Sensitive Hydrogels used for Drug Delivery Environment Typical polymers Main Mechanism Applications al Factor Temperature PNIPAAm, PDEAAm, PEO- Competition between On/off drug release, PPO block copolymers hydrophobic interaction and squeezing device hydrogen bonding pH Polyelectrolytes, PAA, PDEAEM Ionization of polymer chains pH-dependent oral drug upon pH change delivery Glucose pH-sensitive hydrogels; pH change caused by glucose Self-regulated insulin Concanavalin A-grafted oxidase; reversible interaction delivery polymers; polymers containing between glucose-containing phenylborate groups polymers and Concanavalin A; reversible solgel transformation Electric Polyelectrolytes (pH-sensitive) Reversible swelling or Actuator, artificial muscle, signal deswelling in the presence of on off drug release electric field Light Copolymer of PNIPAAm and Temperature change via the Optical switches, light sensitive chromophore, incorporated photosensitive ophthalmic drug delivery such as triphenylmethane and molecules; dissociation into ion leuco derivatives pairs by UV irradiation Antigen Semi-IPN with grafted Competition between polymer- Modulated drug release in antibodies or antigens grafted antigen and free the presence of a specific antigen antigen; sensor for immunoassay and antigen
- 13. Specific applications of Hydrogels in Oral Drug Delivery
- 14. Specific applications of Hydrogels in Oral Drug Delivery Fast-disintegrating tablet formulations fast swelling and superabsorbent properties microparticles of superporous hydrogels mucoadhesive hydrogels • buccal drug delivery Gastric emptying of oral dosage forms • The physical properties (size and density) of the oral dosage form • The presence of food in the stomach Intragastric floating system • low density • float on top of the gastric juice
- 15. Specific applications of Hydrogels in Oral Drug Delivery Mucoadhesive system • cross-linked PAA • highly mucoadhesive at pH (1-3) of the stomach (∵ hydrogen bonding) Superporous hydrogels • Swell to a very large size • High swelling ratio ( > a few hundreds) • Fast swelling property - avoid premature emptying by the housekeeper waves • Gastric retention device (ex. Dogs-from several hours to a day) • Ac-Di-Sol (cross-linked carboxymethylcellulose sodium)
- 16. Specific applications of Hydrogels in Oral Drug Delivery - Hydrotropic Hydrogels for delivery of poorly soluble drug -Hydrotropic agent : Diverse class of water soluble compounds at high concentration, enhance water solubilities of poorly soluble solutes ex) N,N-dimethylnicotinamide (3.5M), N,N- diethylnicotinamide - Many drugs : poorly soluble in water : low absorption and low bioavailability - Low-molecular-weight hydrotropes : high concentration - Polymeric forms of hydrotropes (e.g., hydrotropic hydrogels)
- 17. • Hydrogels have played role in the development of various controlled-release formulation • biocompatible and increasing the solubility of poorly soluble drug • Hydrogels with novel properties will continue to play important role in drug delivery • smart hydrogels and new controlled-release formulation
Notes de l'éditeur
- Swelling ratio 는 하이드로겔이 물을 흡수하는 정도를 나타나는데 이것은 swelling 하이드로겔 무게 값을 dried 된 하이드로겔 무게 값을 뺸 값응 다시 dried 하이드로겔 값으로 나눈 값입니다 . Swelling ratio 는 모노머의 유형과 조성 , 주변환경 요소 , 가교 밀고에 따라 달라 질수 있습니다 . 가교밀도는 하이드로겔의 기계적 강도와 하이드로겔에 물이 침투하는 성질에 많은 영향을 주게 됩니다 . 가교 밀도가 높고 , 하이드로겔이 IPN 구조이면서 소수성 모노머들이 공중합 되어 있으면 기계적 강도는 높아지지만 swelling 은 낮아지게 됩니다 . 이러한 성질을 이용하여 우리가 원하고자 하는 물성을 갖는 하이드로겔을 만들수가 있습니다 .
- 하이드로겔은 화학적 , 물리적 결합으로 이루어진 하이드로겔로 나누어집니다 . 화학적 결합 하이드로겔은 공유결합으로 가교 되어 있으며 열경화서 하이드로겔입니다 . 그리고 부피 상 전이가 일어나며 모양이 안정하고 잘 변하지 않습니다 . 반면에 물리적 결합으로 이루어진 하이드로겔은 수소결합 , 소수성 상호작용 등과 같은 비공유 결합으로 이루어져 있으며 열가소성 하이드로겔입니다 . 이것은 sol-gel transition 이 일어나며 모양 안정성과 그 모양을 유지하는 데 제한적인 특징이 있습니다 .
- 화학적 가교는 두개 이상의 작용기를 가지고 있는 가교제 존재하에서 물에 잘 녹는 모노머들의 중합으로 생성합니다 . 그림에서 보시다시피 모노머가 가교제와 공중합이 일어나면서 하이드로겔 망상조직을 형성하는 것과 vinyl 그룹을 가진 물에 잘녹는 고분자를 중합하여 하이드로겔 망상조직을 생성할 수 있습니다 . 이것은 앞에서 말했다시피 공유결합으로 이루어진 화학적 결합으로 이루어진 하이드로겔입니다 .
- 첫번째는 물에 잘 녹는 고분자를 이용하여 그 안에 약물을 봉입하여 그것이 시간이 지남에 따라 약물이 고분자 밖으로 방출되는 방법입니다 . 둘째는 물에 잘녹는 고분자 membrane 을 이용하여 그안에 약물을 봉입하여 이것도 시간에 따라 약물이 서서히 membrane 밖으로 방출되는 방법입니다 . 두가지 모두다 중심에는 약물이 있고 , 약물 주위에는 물에 잘 녹는 고분자를 둘러 쌈으로 인해 우리 몸 안에 들어가게 되면 circulation time 이 좋게 할 뿐만 아니라 하이드로겔의 swelling ratio 에 따라 약물의 방출 속도를 조절할 수 있다는 특징이 있습니다 .