An Overview on IPN and its Medicinal applications

 

Sanyogita Rajendra Patil, Shweta Rajendra Patil, Rutuja R. Shah

¹Anandi College of Pharmacy, Kalambe Tarf Kale, Bhamate, Maharashtra.

 

ABSTRACT:

Interpenetrating polymer network (IPN) is regarded as one of the most useful novel biomaterial. The invention of IPN can be rendered biocompatible and biodegradable has far reaching and profound long‐term implications for the pharmaceutical industry and indeed medicine as a whole. The excellent biocompatibility and safety due to its physical characteristics such as impart stability of the drug in the formulations, improves solubility of hydrophobic drugs, excellent swelling capacity and its biological characteristics, like biodegradability, impart bioavailability, drug targeting in a specific tissue and very weak antigenicity, made IPN the primary resource in both pharmaceutical and medical applications IPNs, two or more networks are at least partially interlaced on a polymer scale. Base on applications, polymers and polymer networks needs to have certain properties. IPNs can be used with interpenetration of suitable polymers to have desired properties for specific applications. The potential applications of IPN as drug delivery systems specially for the controlled release drug delivery systems. It was also used for tissue engineering including bone substitutes, stationary phase and cartilage scaffolds These systems which are also termed as ‘hungry networks’ or ‘intelligent polymers’ are currently the focus of considerable scientific research due to their potential technological application in a large number of areas: medicine, industry, biology and environmental clean-up. Some of the significant applications of IPNs include artificial implants, dialysis membranes, drug-delivery systems, burn-dressings, etc Interpenetrating polymer network has scope for its use as carrier system in drug delivery system. Characteristics of rubber can be modified by using different reinforcements.

 

 

INTRODUCTION:

An interpenetrating polymer network is a polymer containing two or more networks which are at least partially interlaced on a polymer scale but not covalently bonded to each other. The network cannot be separated unless chemical bond arebroken¹. Interpenetrating polymer networks (IPNs) are described as a combination of two or more polymers synthesised in juxtaposition and organised as networks.

 

Before modern understanding of morphology and phase separation, the phrase “interpenetrating polymer network” was developed.

 

 

The majority of IPNs do not interpenetrate on a molecular scale, as we now know. However, some IPNs have been shown to form finely separated phases that are barely tens of nanometers in size. Numerous IPNs display Dual phase continuity refers to the existence of phases that are continuous on a macroscopic scale when two or more polymers are present in the system². Applications for polymers range from the medicinal profession to the aviation industry. other significant applications Drug delivery systems, biosensor devices, tissue engineering, and cosmetics are all examples of polymer applications. Polymer is created when comparable components are joined together.³

 

Due to their convenient means of modifying their properties to suit particular requirements, multi-polymers’ chemical and physical combination methods and properties have attracted a considerable deal of practical and academic interest for the controlled release of pharmaceuticals. Among There has been a lot of interest in the creation of IPN-based medication delivery systems because of these techniques. This would create new opportunities for using IPN in the development of cutting-edge controlled release medication release systems.⁴

 

For the successful development of IPN-based SMPs, the network features are predicted to play a significant role in regulating the shape memory performance in an IPN system.⁷ IPNs made of PVA and chitosan were created in the current study by UV irradiation. This study focuses on the creation, characterisation, and pH/temperature dependence of swelling for PVA and chitosan-based IPN hydrogels.⁸ The study of an IPN's swelling pattern is crucial because it provides information about the network structure of the IPN as well as the mechanisms of the water transport processes at play, in addition to describing the water content of the IPN at equilibrium.⁹ Ion-exchange resin, impact-modifier for thermoset materials, rimplast thermoplastics, pressure-sensitive adhesives, coatings materials, dental fillings, selective/permeable membranes, sound and vibration damping, tough rubber and plastic materials, and artificial joints are just a few examples of the important materials that use IPNs extensively.¹⁰

 

MERITS OF IPN⁵:

In modern era polymer IPN system gaining huge populantaly its following inherent advantages

·       Physical phase separation between the component polymers would be nearly impossible whenever an IPN hydrogel is created from two polymers at a specific temperature.

·       IPN Is also appealing in developing synergistic qualities from the component polymers because of the gel’s infinite zero viscosity.

·       IPN systems are known to increase the phase stability of the final product.

·       IPN enhance the mechanical properties of the final product, for example, when a hydrophilic gelling polymer is interpenetrated with a relatively hydrophobic gelling polymer, the resulting IPN hydrogel is expected to have an improved capability of immobilising a drug.

·       Due to the permanent interlocking of the network segments, thermodynamic incompatibility can be overcome as long as the reactive materials are completely mixed together during the synthesis.

 

Classification of IPN ⁴:

 

Fig. 1 Classification of IPN

 

·       Based on arrangement pattern:

1.     Covalent semi IPN -In a covalent semi IPN, two different polymer systems are crosslinked to create a single polymer network

2.     Non- covalent semi IPN- A non- covalent semi IPN is one in which only one of the polymer system is crosslinked.

 

    Network A         Linear chain B      Semi – IPN (A+B)

 

    Network A           Network B         Full – IPN (A+B)

 

 

Fig.4 Novel IPN

 

Fig.5 Sequential IPN

 

·       Based on chemical bonding:

1. Novel IPN:

Polymer consist two or more polymer networks which are at least partially interlocked on a molecular scale but not covalently bonded to each other and cannot be separated unless chemical bonds are broken.

2. Sequential IPN:

In sequential IPN the second polymeric component network is polymerised following the completion of polymerization of the first component network.

3. Simultaneous IPN: Simultaneous IPN is prepared by a process in which both component networks are polymerized concurrently, the IPN may be referred to as a simultaneous IPN.

 

Fig.6 Simultaneous IPN

 

1.     Semi IPN:

If only one component of the assembly is cross linked leaving the other in a linear form, the system is termed as semi IPN.

 

·       Method of preparation of IPN⁶:

1.     Inotropic granulation method:

This method relies on the interaction of an ionic polymer and a polymer having an opposite charge. In order to ensure total solubility, sodium alginate and the polymer were completely mixed, disseminated, and combined in distilled water. With the use of 23 gauze syringe needles, the solution was then added dropwise to another aqueous medium containing an additional ionic polymer (Al+3, Ca+2, etc.) while being continuously stirred.

 

2.     Emulsification cross linking:

Phase separation is the foundation of this process. This technique is frequently used to create cross-linked polymer networks. Usually, awater-in-oil (w/o) emulsion is used to prepare the cross-linked. Aqueous without emulsification.

 

By stirring the water-soluble polymer into a homogenous solution, polymeric solution was created. The oil phase was then supplemented with this aqueous phase. Water-in-water (w/w) emulsion has recently been developed to create IPN. Since there is no use of an organic solvent and the w/w emulsification technique solely relies on the aqueous environment, the toxicity effect of w/w emulsion is less than that of w/o emulsion.

 

3.     Free radical polymerization:

The principal use of free radical polymerization is the creation of polymers. It is a method of polymerization where a polymer is created by adding free radicals one after the other. The free radical website is first developed on the chain extension method, the chemical component is subsequently bonded to the backbone polymer. When compared to other ionic chain-growth reactions, the effect of adventitious impurities is significantly less.

 

First, the polymer was dissolved in distilled water in a round-bottom flask. The nitrogen gas is then continuously passed through the system while being heated to 80°C for 4 hours. This mixture received the addition of a second polymer along with an initiator. Nitrogen gas is continuously applied throughout this operation for one hour. The grafted copolymer was cured after one hour.

 

4.     Wet granulation method:

Wet granulation is a process that combines dry powder with granulating fluid that may be dried out and removed. Aqueous or solvent-based solutions are both acceptable for use in granulation.The necessary amount of polymer is manually mixed for 15 minutes. When the cohesive mass is ready, the necessary amount of blending agent is added, and the wet mass is then passed through a # 22/24 mesh screen. The final product is dried for 12 hours at 40° to 60°C. After the drying process was finished, a #22 mesh screen was used to filter the dry granules. The granules were then combined with magnesium stearate and compacted into a tablet.

·       Applications:

♦    Therapeutic Application of IPN Based Drug delivery System⁴

§  Virus and infection:

Rats tissue responses to full and semi-IPNs containing polyacrylic acid and gelatin  loaded with genramicin sulphate were assessed, and the absence of any extra local or systemic reaction suggests the hydrogels potential value as drug delivery system.

 

§  Cancer Treatment:

Collagen and chitosan were combined to create an interpenetrating polymeric network (IPN), a biodegradable polymer scaffold for the in vitro cultivation of human epidermoid carcinoma cells (HEp-2). The findings of the aforementioned research indicate that collagen and chitosan scaffolds can be employed as a substrate for HEp-2 cell culture and as an in vitro model for testing anti-cancerous medicines. The development of a biodegradable polymer scaffold employing interpenetrating polymeric networks made of collagen and chitosan to cultivate human epidermoid carcinoma cells (HEp-2, Cincinnati) in vitro. To create the scaffold, glutaraldehyde was utilised as a cross-linking agent. HEp-2 cells were used for in vitro culture investigations over the chosen scaffold, and the growth morphology was assessed using optical images captured at various magnifications on different days of culture. The findings of the aforementioned investigations indicate that collagen and chitosan scaffolds can be employed as a substrate for HEp-2 cell culture and as an in vitro model for testing anticancer medicines

 

§  Treatment for Chronic Pain:

Using a biocompatible, biodegradable copolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), and another biocompatible but synthetic, non-degradable polymer, poly (2-hydroxyethyl methacrylate), which shows prominent actions to relief from chronic pain, a controlled release system for local application of analgesics hydromorphone, morphine, and codeine and a local anaesthetic, bupivacaine loaded In this study, we investigated the cell-surface interactions between aortic endothelial cells (ECs) and a poly (acrylamide-co polyethylene glycol/acrylic acid) interpenetrating network (IPN) hydrogel. No matter the RGD surface concentration, ECs moved and multiplied rapidly. According to these findings, this IPN may be employed to encourage endothelialization of vascular implants consisting of polymeric and metal materials for cardiovascular applications. Different collagen and elastin combinations demonstrated a controlled delivery system for drugs used in the heart and blood vessels. A regulated distribution system like this one is used to mimic the calcification of implantable biomaterials like the bioprosthetic heart valve (BHV). The aortic leaflet and wall have mostly been used as calcifiable matrix in BHV. Due to rising concerns, the calcification of the bioprosthetic aorta wall has recently received substantial research

 

§  Cardiac disease treatment:

 In this study, we investigated the cell-surface interactions between aortic endothelial  cells (ECs) and a poly (acrylamide-co polyethylene glycol/acrylic acid) interpenetrating network (IPN) hydrogel. No matter the RGD surface concentration, ECs moved and multiplied rapidly. According to these findings, this IPN may be employed to encourage endothelialization of vascular implants consisting of polymeric and metal materials for cardiovascular applications. Different collagen and elastin combinations demonstrated a controlled delivery system for drugs used in the heart and blood vessels. A regulated distribution system like this one is used to mimic the calcification of implantable biomaterials like the bioprosthetic heart valve (BHV). The aortic leaflet and wall have mostly been used as calcifiable matrix in BHV. Due to rising concerns, the calcification of the bioprosthetic aorta wall has recently received substantial research.

 

§  Immunotherapy:

Degradation of an implanted substance begins with the capacity of monocytes to attach, develop into macrophages, and unite to create foreign body giant cells (FBGCS). To mediate adhesion, novel homogenous surfaces were employed. N-(2 aminoethyl)-3- aminopropyltrimethoxysilane (EDS) and an IPN (IPN) of polyacrylamide and poly(ethylene glycol) made up these surfaces. These surfaces were created to regulate cell adhesion and shape as well as mediate cell differentiation, activation, metabolic capacity, and death, which in turn led to a diminished or under control inflammatory response. The IPN reduces protein adsorption and subsequent cell adhesion, whereas the EDS surface enhances cell adhesion .

 

♦    Drug Delivery Systems Based on IPN for Tissue Engineering⁵

§  As bone substitutes, IPN:

The creation of bone serves as a prototype model for tissue engineering based on morphogenesis and has been recognised as a potent marker for regeneration among the diverse tissues in the human body. For example, collagen was also employed to treat orthopaedic deformities in combination with other polymers or chemicals. Both acquired and congenital orthopaedic abnormalities were treated with demineralized bone collagen as a bone graft material, either alone or in conjunction with hydroxyapatite 61. The outcome of this investigation demonstrated the superior osteoinductive properties of grafted demineralized bone collagen combined with hydroxyapatite, which might be employed as a bone substitute. A nonfouling, enzymatically degradable IPN (edIPN) of poly(AAm-co-EG/AAC) capable of presenting the cell signalling domain Arg-Gly- Asp (RGD) was created to evaluate the relative impacts of implant surface chemistry and topography on osseointegration within the rat femoral ablation implant paradigm. After 28 days, the use of the enzymatically degradable IPN (edIPN) without peptide modification resulted in a moderate improvement of periimplant bone growth. In an effort to control bone formation in the peri-implant region in the rat femoral ablation model, IPNs of poly(acrylamide-co-ethylene glycol/acrylic acid) functionalized with a - Arg-Gly-Asp- (RGD) containing 15 amino acid peptides, derived from rat bone sialoprotein (bsp-RGD, were grafted to titanium implants

 

§  Bioengineered tissues as IPN:

On the basis of solutions of two or more polymers that form semiinterpenetrating or IPNS upon exposure to active species following injection at a site in a patient in need thereof, compositions for tissue engineering and medication administration have been created. Only one of the polymers needs to crosslink for semi-interpenetrating networks to form because the polymers do not crosslink to one another. The resulting viscous solutions keep the biologically active chemicals or cells where they were injected until they are released or, in the case of cells, until tissue development happens. Recent developments in tissue engineering could result in the development of characterised, repeatable biomaterials based on natural IPN materials. Collagen-based matrix made from biological tissue grafts from the bladder, ureter, or small intestine has been used in these procedures. In terms of their durability, these collagen structures were made to resemble synthetic polymer prostheses. The link between the structure and mechanical behaviour of biomaterials derived from the gut submucosa showed mechanical anisotropy and the preference for stiffer directions in biomaterials . signals surrounding stem cells that are strictly regulated, A number of factors have been linked to influencing stem cell proliferation and maturation, including growth hormones at particular concentrations and matrix mechanical stiffness. We define a strong synthetic and precisely specified platform for the cultivation of adult brain stem cells using a biomimetic interfacial IPN. Two ligands that attach to cells were added to IPNs

 

§  A cartilage scaffold used by IPN:

In this study, freeze-drying was used to create alginate and alginate:chitosan semi IPN scaffolds. These structural and cellular results show the chitosan semi IPNs' potential utility in alginate scaffolds. Results from comparisons with alginate scaffolds show that alginate: chitosan scaffolds are essential for better cartilage tissue engineering.

 

♦    Aeronautics applications³:

Ceramics and Silicon carbide-based composite materials have several uses in the aerospace, energy, and industrial industries. Commercially accessible silicon carbide has a limited temperature range. Singh created interpenetrating phase composites based on silicon carbide. He contends that the interpenetrating approach offers more morphological control. microscopic structure

 

§  Elastomers:

Elastomer characteristics are improved by interpenetrating polymer networks. Crosslinking of commercial silicon elastomers can enhance the properties of dielectric elastomers, which in turn can improve the properties of sensors, elastomers, and actuators.

 

§  Enhancement of tribological characteristics

Tribology is the study of interacting surfaces, including friction, lubrication, and wear. By adding secondary phase, interpenetrating materials' tribological properties can be improved. Wang et al. claim that there is hardly any research material accessible for the examination of interpenetrating composites' abrasion resistance. They investigated the dry sliding interpenetrating behaviour of the interpenetrating polymer Si3N4/AlSi11. They separated abrasive wears into four categories. Initial adhesive, mixed adhesive, abrasive wear, and final abrasive wear are the six. According to their studies, reinforcing significantly boosted the materials' abrasion resistance.

 

§  Reducing the vibration produced by moving machinery -

Vibration levels of moving machines and parts can be reduced by using polymers with good viscoelastic characteristics. The viscoelastic qualities may be enhanced by the expansion of the glass transition area. Poly (methyl methacrylate)/epoxy (PMMA/EP) interpenetration networks were examined by Jia et al. for the research of mechanical, thermal, and dampening qualities. They noticed that the thermal stability decreased as the PMMA level rose. The glass transition region was greatly widened during the penetration of PMMA into epoxy. Clearly, this will aid in enhancing vibrational characteristics. Dolata conducted a comparative analysis of the tribological characteristics of unreinforced AlSi12 matrix areas and interpenetrating composite layers made of AlSi12 and Al2O3. According to this study, the reinforcement increases wear resistance and stability caused by friction in the substance. Kamal investigated the formation of an interpenetrating polymer network using polyantimonyacrylate and camphor. According to this study, Active Poly[2-(sec-butyl) aniline] PSBA injection causes edoema to increase. Additionally, the investigator noticed that the Young's modulus increased as PSBA concentration increased

 

♦    Medical Application:³

Natural polymers have good enough properties for medical applications. Interpenetration and interpenetrating network is a widely investigated area of polymer material science because the properties of a polymer, like polylactic acid, can be improved by using interpenetration. Polylactic acid is widely used in biological applications because it is biodegradable. It has the second-largest consumption of any bioplastic in the world. Polyhydroxyethyl methacrylate also has good biocompatibility. Passos et al. carried out an investigation to improve the properties of polylactic acid by using poly 2-hydroxyethyl methacrylate and found that there was a decrease in glass transition temperature and melting temperature. Based on chemical bonding, interpenetrating networks can be classified as cross semi IPN, non-covalent semi IPN, non-covalent full IPN. Various arrangement patterns can be used in interpenetration. Fossil fuel is the source of many polymers and macromolecular products. Their resistance to water and other chemical compounds, durability, and flexibility make them valuable products. Depleting reservoirs and rising fossil fuel prices call for the use of other alternatives, such as biopolymers, which can be recycled. Interpenetrating network structure can be used to impart special properties. Multifunctional monomer polymerization is a high-speed and low-temperature reaction. Kaczmarek and Kwiatkowska carried out an investigation for the interpenetration network of polyacrylates and poly lactic acid and observed that the initial morphology of substances has a strong effect on polymerization.

 

§  Membranes:

An Interpolymer network (IPN) structure can be used to improve the properties of membranes, such as mechanical strength and selectivity. Lim and Kim investigated the separation of water and ethanol mixtures by using composite membranes. These composite membranes were prepared with a polyacrylic acid-poly(butyl methacrylate-co-methyl methacrylate) interpenetrating polymer network (PAA-P(BMA-co-MMA) (IPN)). This was skin layer supported on a cross-linked and porous poly(BMA-co-MMA). With the use of 70 percent N-methyl-2-pyrrolidone (NMP), they were able to create a highly porous cross-linked structure.

 

§  Polymer electrolytes:

Rahman et al. used Chitosan obtained from chitin, as base raw material for synthesis of O-nitro chitosan. They observed that the chitosan derived modified material has improved properties than poly (NIPAAm) hydrogel. Use of organic solvents in batteries is unsafe because of the volatile and flammable properties of these solvents. Gel polymer electrolytes (GPE)can be used to suppress the volatility of the solvents. Stability of gel polymer electrolyte can be improved by using chemical cross linking. The interaction between the electrolyte and ethylene oxide makes them promising gel base for gel polymer electrolytes. Lua et al. synthesized gel polymer electrolyte membrane. Due to advantages in time, energy and process control, they used UV light irradiation curing. According to their studies, the mechanical properties are improved due to the cross-linked poly (ethylene glycol) diacrylate-co-poly (vinylene carbonate) P(EGDA-co-VC), P(EGDA-co-VC) copolymer. Also, poly (vinylidene fluoride- cohexafluoropropylene (PVDF-HFP), PVDF-HFP polymer increases the toughness and flexibility. Excellent results were obtained by Prashantha et al., by using glycerol modified castor oil polyurethane interpenetration with PHEMA.

 

§  Charge dissipaters:

The interpenetration resulted in increased chemical resistance, hardness, elongation and tensile properties. Intrinsically conducting polymers find application as charge dissipaters for e-beam lithography. They have many other applications including corrosion protection, artificial muscles, light-emitting diodes, field-effect transistors, photovoltaic cells, batteries. Dopants are used in these materials to obtain certain electrical properties and change conductivity of these materials

 

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Received on 27.05.2023         Modified on 22.06.2023

Accepted on 24.07.2023  ©Asian Pharma Press All Right Reserved