Polyelectrolyte Complexes a Review of Their Applicability in Drug Delivery Technology

Indian J Pharm Sci. 2009 Sep-Oct; 71(5): 481–487.

Polyelectrolyte Complexes: A Review of their Applicability in Drug Delivery Technology

S. Lankalapalli

Raghu College of Chemist's, Dakamarri, Bheemunipatnam, Visakhapatnam 531 162, India

Five. R. Grand. Kolapalli

1Academy College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 003, India

Received 2009 Mar ix; Revised 2009 Aug 11; Accepted 2009 Aug 20.

Abstract

Over the by several years, great advances have been fabricated towards novel drug delivery systems. The phenomena of interpolymer interactions and formation of polyelectrolyte complexes have been the focus of intensive fundamental and practical research. Interpolyelectrolyte complexes combine unique physicochemical properties with high biocompatibility. Studies accept been carried out on many different polymer blends and types. Such combinations may possess unique properties that are different from those of private component. The present review emphasizes on the applicability of polyelectrolyte complexes in drug delivery engineering science.

Keywords: Polyelectrolyte complex, polymer, drug commitment, polyion, electrostatic interaction

Current state of art is witnessing a revolution in new techniques for drug delivery. These techniques are capable of controlling the charge per unit of drug commitment, sustaining the elapsing of therapeutic activity and/or targeting the drug to specific tissues. These advancements led to the development of several novel drug delivery systems, revolutionizing the medication with several advantages.

Recent decades witnessed the advent of polymers that respond in some desired mode to changes in temperature, pH, electrical or magnetic field. The driving force backside these transitions include stimuli like neutralization of charged groups by either a pH shift or the addition of an oppositely charged polymer, changes in the efficiency of hydrogen bonding with an increase in temperature or ionic forcefulness and collapse of hydrogels and interpenetration of polymer network. These types of polymers not only convert the active substances into a non-deleterious form which tin can be administered, but likewise accept specific effect on the biodistribution, bioavailability or absorption of the active substances and hence increasingly gaining importance in modern pharmaceutical engineering science. The interaction between 2 oppositely charged polymers results in the formation of a complex, termed as polyelectrolyte complex[i]. These polyelectrolyte complexes meet the contour of requirements of biocompatible polymer systems and can be adapted to meet the various requirements like carrier substances and components for active substances.

Polyelectrolyte complexes (PECs) are the association complexes formed between oppositely charged particles (e.g. polymer-polymer, polymer-drug and polymer-drug-polymer). These are formed due to electrostatic interaction between oppositely charged polyions. This avoids the use of chemical cross linking agents, thereby reducing the possible toxicity and other undesirable effects of the reagents. The polyelectrolyte complexes formed between a poly acrid and poly base of operations are little afflicted by the pH variation of the dissolution medium. This concept of complexation, betwixt Deoxyribonucleic acid and chitosan[2], has extensively been studied in the development of delivery vehicle for cistron therapy and oral vaccination.

The occurrences of charge-charge interactions betwixt ionic polymers and drugs were considered to be a negative event when the ionic polymers are used every bit excipients in pharmaceutical formulations. In these systems release of drugs may exist strongly affected by the occurrence of charge-charge interactions. Nonetheless, in recent years these negative events of polymer-drug and polymer-polymer interactions have been exploited positively for controlled drug release[3,four].

Polyelectrolytes:

The polymers that contain a net negative or positive accuse at nigh neutral pH are called polyelectrolytes[5]. They are by and large soluble in water. Their solubility is driven by the electrostatic interactions between water and the charged monomer. Examples of such polymers include DNA, protein, certain derivatives of cellulose polymers and carragenan.

Classification of polyelectrolytes[6]:

The polyelectrolytes are classified into various types. Based on origin they are classified as natural polyelectrolytes, synthetic polyelectrolytes and chemically modified biopolymers. Based on limerick they are homopolymers and copolymers. Based on molecular architecture linear, branched and cross linked. Based on electrochemistry they are classified equally polyacids/polyanions, polybases/polycations and polyampholytes. Some of the important polyelectrolytes are exemplified in Table one.

TABLE 1

SOME OF THE Important POLYELECTROLYTES

Name Category (based on the charge type)
Natural Polyelectrolytes
 Nucleic acids Polyanion
 Poly (L-lysine) Polycation
 Poly (50-glutamic acid) Polyanion
 Carrageenan Polyanion
 Alginates Polyanion
 Hyaluronic acid Polyanion
Chemically modified biopolymers
 Pectin Polyanion
 Chitosan (deacetylation of chitin) Polycation
 Cellulose - based Polyanion or polycation
 Starch - based Polyanion or polycation
 Dextran - based Polyanion or polycation
Constructed polyelectrolytes
 Poly (vinylbenzyl trialkyl ammonium) Polycation
 Poly (4-vinyl-North-alkyl-pyridimiun) Polycation
 Poly (acryloyl-oxyalkyl-trialkyl ammonium) Polycation
 Poly (acryamidoalkyl-trialkyl ammonium) Polycation
 Poly (diallydimethyl-ammonium) Polycation
 Poly (styrenesulfonic acid) Polyanion
 Poly (vinylsulfonic acid0 Polyanion
 Poly (acrylic or methacrylic acid) Polyanion
 Poly (itaconic acid) Polyanion
 Maleic acid/ diallyamine copolymer Polyampholytic

Theoretical aspects of PECs:

Many researchers extensively investigated the properties of the polyelectrolytes[half-dozen,7] and the germination of PECs[8–10]. In that location have been theories proposed based on the electrostatic forces and Flory-Huggins mixing free energies of the polyelectrolytes to explain the mechanism of formation of PECs[xi–13]. In full general the backbones of the two polymers are not uniform and repel to each other, notwithstanding, the charge fraction of the polymers determines the type of interaction going to occur betwixt the polymers. When the charge fraction is low, the polymer courage repulsion (Flory interaction parameter) is ascendant and the solution separates in to two phases each containing more often than not 1 of the polymers. At high accuse fraction, the attractive electrostatic interactions between the polymers dominate and they precipitate to form a complex. In an intermediate range of charge fraction, the equilibrium country can be a meso stage where the two polymers simply separate microscopically. Depending on the stoichiometry of the mixture (the relative concentrations, the relative concatenation lengths and accuse densities), one observes mainly 2 types of complex formations, a macroscopic phase separation between the solvent and the polymers or a fractional aggregation of the polymer chains[14].

Formation of PECs:

This procedure involves mainly 3 steps equally shown in fig. 1[15]. Outset step is master complex formation and Coulomb forces are responsible for this pace. Second step is germination process within intracomplexes. Information technology involves formation of new bonds and/or the correction of the distortions of the polymer chains. Third is intercomplex aggregation process, which involves the aggregation of secondary complexes mainly through hydrophobic interactions.

An external file that holds a picture, illustration, etc.  Object name is IJPhS-71-481-g001.jpg

Schematic representation of the formation and aggregation of PECs

(a) Main complex formation (b) Formation process within intracomplexes (c) Inter complex aggregation process

Factors affecting the formation of PECs:

A number of parameters are known to influence the formation of PECs[sixteen]. These are ion site, charge density, polyelectrolyte concentration, pH, ionic forcefulness, solvents and temperature. Several workers evaluated the factors effecting the formation of polyelectrolyte complexes with different polymeric blends[17,eighteen]. Atmospheric precipitation is caused by effective attractions due to charge fluctuations and past short range attractions between monomers. Interesting in the context of the polyion stoichiometry are studies of layer formation from strongly asymmetric pairs of polyions. Employing polyions with a reduced charge density forth the chain, i.due east. consisting of charged and uncharged co-monomers, it was observed that a minimum charge density[19] is required for polyelectrolyte adsorption. Changing the ionic force past addition of salt[twenty] tin can modulate the electrostatic interactions in a polyelectrolyte solution. The electrostatic interactions can be weakened by addition of inorganic salts into the solutions. Thus, an increase of the ionic strength of the solution depresses the complexation between polyions, because of the screening of opposite charges of the macromolecules by low molecular weight ions. By varying the pH environment during PEC formation, the caste of ionization of weak polyelectrolytes can exist controlled[21,22]. This was found to touch on multilayer properties such as layer thickness, the caste of interpenetration betwixt layers, surface wettability and number of unbound functional groups. Therefore, past choosing the correct pH atmospheric condition, a platform may be found with properties that are advantageous for loading charged pocket-size molecules into the film via electrostatic interactions.

Characterization of PECs:

Diverse methods have been used to investigate interactions between polymers[23]. Measurements of turbidity, pH and ionic strength[24,25] equally a office of weight ratio of polymer in the media[26], viscosity[27], lite handful[28,29], infrared spectroscopy, NMR, thermal assay, pKa and pulverization X-ray diffraction[thirty] were employed to evaluate interpolymer complexation.

Applications of PECs:

PECs have gained much attention in the past few years because of their potential applications. These can exist used as membranes[31–33], for coating on films and fibers[34], for isolation and fractionation of proteins[35,36], for isolation of nucleic acrid[37–39], for binding pharmaceutical products[40], as supports for catalyst[41] and for preparation of microcapsules for drug delivery[42,43]. Many of the applications are based on the functional properties of the polyelectrolyte. The functional applications of PECs are summarized in Tabular array 2.

TABLE 2

PRACTICAL Awarding OF POLYELECTROLYTE COMPLEXES

Functional property Application
Interaction with counter ions Support of filtration process - removal of counter ions[61,62]
Gelation process - bridging with multivalent counter ions[63]
Analytical methods - counter ion exchange[64]
Interaction with surfactants Insoluble polyion surfactant complex for depression energy surface modification[65]
Highly ordered structures (micelle) formation[66,67]
Interaction with charged low molar mass molecules Polyion drug complexes - soluble or insoluble[68]
Interaction with charged particles Floculation - waste product water treatment[69]
Dewatering - sludge, pulp and newspaper production[70]
Flotation - mining
Retentivity - newspaper product
Interaction with charged surfaces Displacement chromatography - separation and concentration of biomolecules[38]
Modification of surfaces and interfaces - blanket (antistatic, sensors, multi-layer)[71,72]
Condiment (cosmetics, detergents)

The concept of PECs in the design of drug commitment systems may exist useful due to the advancements made during the last two decades[44–47]. The active components will be encapsulated in the polymer matrix at molecular level. They offering greater advantages for the drug substances through improving/and altering physicochemical characters similar stability and dissolution. The active substance tin exist incorporated in to PECs past four ways[48]. In the first case the active substance volition be entrapped from the solution during atmospheric precipitation of the complex. The agile substance will exist absorbed from the solution and gets incorporated in to the already formed circuitous on contact in the second case. In the third example the active substance may be chemically bound to at least one complex partner and precipitates during complexation. In the terminal case the agile chemical compound itself may act as poly ion and form PEC. The active substance from these PECs will exist released either by solution equilibration or by ion substitution mechanism or by accuse interaction and deadening decomplexation as well every bit breakdown and dissolution of the circuitous.

There are several reports on different methods of preparation and applications of PECs in chemist's shop. Kawashima et al.[49] developed a novel method for the preparation of theophylline granules coated with a PEC of sodium tripolyphosphate and chitosan. The theophylline granules containing sodium tripolyphosphate were stirred in an HCl solution of chitosan. During the mixing, the dissolved sodium tripolyphosphate in the granules moved to the surface and reacted with the chitosan, resulting in the formation of a PEC film. The drug-release design of the coated granules followed zero-gild kinetics and the release rates were significantly reduced compared with that of the original granules.

Shiraishi et al.[fifty] studied the controlled drug release behaviour of indomethacin by chitosan-PEC. They too optimized the formulation conditions and reported its in-vivo/in-vitro evaluation studies. They prepared the PEC of indomethacin by using complexation of sodium tripolyphosphate and chitosan. Here the effects of the molecular weights of chitosan hydrolysates on the release and assimilation rates of indomethacin from gel beads were examined. The release rates of indomethacin decreased with increasing of molecular weight and indomethacin content. A negative correlation was observed between the molecular weight and release rate constant (r=−0.983).

Jimenez-Kairuz et al.[51] developed and characterized swellable drug-polyelectrolyte matrices (SDPM) using carbomer and different basic drugs similar atenelol, lidocaine and metoclopramide. The authors ended that drugs can be loaded in a high proportion on to the polymer and therefore the resulting SDPM material could be diluted with other polymers to modulate commitment backdrop of SDPM. Matrices of atenolol and lidocaine exhibited robust delivery properties with regard to change in proportion of loading drug. Liao et al.[52] prepared drug-loaded chitosan-alginate fibers by interfacial polyelectrolyte complexation technique. Depending on the component properties, the release time of encapsulated components from these fibers could range from hours to weeks. Dexamethasone was completely released within ii h, whereas charged compounds such as bovine serum albumin, PDGF-bb, and avidin showed sustained release for three west. In this study, interfacial polyelectrolyte complexation demonstrated to exist a promising technique for producing drug-loaded fibers with loftier encapsulation efficiency, sustained release kinetics, and capacity to retain the bioactivity of the encapsulants.

Tapia et al.[53] evaluated the possibility of using mixtures of PECs from both chitosan (CS)-alginate and CS-carrageenan as prolonged release systems. Different dissolution profiles for diltiazem clorhydrate were obtained by irresolute the polymer matrix organisation (CS-alginate or CS-carrageenan) and the method used to include these polymers into the formulation (physical mixture or PEC). Drug dissolution profiles from the matrices have been discussed by considering the swelling behavior of the polymers used. They reported that CS-alginate systems were considered to be ameliorate in prolonging the release when compared to CS-carrageenan systems.

Paloma et al.[54] prepared polyionic complexes of CS and poly(acrylic acid) (PAA) in a wide range of copolymer limerick and with two kinds of drugs. Release of amoxicillin trihydrate and amoxicillin sodium from these different complexes was studied. The swelling behavior of and solute ship in swellable hydrogels were investigated to cheque the effect of polymer/polymer and polymer/drugs interactions. The electrostatic polymer/polymer interactions took place betwixt the cationic groups from CS and the anionic ones from PAA. The diffusion of amoxicillin trihydrate was controlled but past the swelling/eroding ratio of the polyionic complexes. The swelling degree of amoxicillin sodium hydrogels was more than all-encompassing when compared to the swelling degree of amoxicillin trihydrate formulations. It was concluded that the water uptake was mainly governed by the degree of ionization. Restriction of amoxicillin sodium diffusion could be achieved by polymer/ionized-drug interaction that retards the drug release. Win et al.[55] developed PEC gel chaplet based on phosphorylated chitosan (PCS) for controlled release of ibuprofen in oral administration. The PCS gel beads were prepared from soluble phosphorylated chitosan by using an ionotropic gelation with counter polyanion, tripolyphosphate (TPP) at pH 4. Surface morphology studies for the prepared beads were washed past using SEM. The percentage release of ibuprofen from PCS gel beads was found to be increased as the pH of the dissolution medium increased. The release rate of ibuprofen at pH 7.iv was higher than the release charge per unit at pH 1.4 due to the ionization of phosphate grouping and college solubility of ibuprofen at pH 7.4 medium. The ability of the prepared copolymer to exist used every bit drug carrier for colon-specific drug delivery arrangement was estimated using ketoprofen as model drug.

Albeno et al.[56] obtained a patent for preparation of stable water insoluble complexes of poorly soluble compounds molecularly dispersed in water insoluble ionic polymers. The compounds were micro precipitated in the ionic polymers in amorphous form. The complexes according to the nowadays invention significantly increased the bioavailability of poorly soluble therapeutically active compounds.

Rolfes et al.[57] reported a method of making a solid interpolymer circuitous for use as a controlled release matrix for oral assistants. The process involved mixing of 2 oppositely charged polymers and spray-dried to evaporate the solvent and to prepare solid particles of interpolymer complex. An active agent such every bit drug can be preferably embedded or encapsulated in the interpolymer complex before spray drying or may be incorporated by suitable ways at a later stage. Mi et al.[58] employed enzyme hydrolyzed CS to prepare CS tripolyphosphate and CS polyphosphoric acid gel chaplet using a polyelectrolyte complexation method for the sustained release of anticancer agent, 6-mercaptopurine. Nandini and Cherng-Ju[59] developed drug PECs with poly(acrylamido-2-methyl-1-propansulfonate sodium-co-methyl-methacrylate. They studied and reported that the release kinetics were strongly dependent on the drug solubility rather than on the type of amine in the drug. The release of drugs from the tablets of drug-poly(acrylamide-ii-methyl-1-propane sulfonate sodium-co-methyl methacrylate circuitous were well described by the dissociation/erosion mechanism. Petzold et al.[60] prepared dissimilar PECs from poly(diallyl-dimethyl-ammoniumchloride) and two different polyanions and characterized their application as flocculants. The results showed that the most important advantages of PEC were the loftier velocity of sedimentation and a very broad range of the optimum flocculation concentration.

The review summarized emerging popularity and valuable potential offered past the polyelectrolyte complexes in the field of drug delivery. They correspond an attractive form of polymer-based materials finding an irreplaceable role in many areas of the everyday life used for the preparation of biodegradable and biocompatible three-dimensional membranes, microcapsules, nano-sized formulations and various types of controlled release drug delivery systems.

CONCULSIONS

An all-encompassing research is going on in the area of polyelectrolytes and polyelectrolyte complexes. At that place is a neat potential in utilizing these PECs in ecology, biotechnology, medicine and pharmaceutical applied science. However these techniques are not finer applied for the evolution of drug delivery systems. They may efficiently alter the release; improve the stability and character of the drug substances due to their capacity to entrap the drug at molecular level. Hence the polyelectrolyte complexes have great potential in the design of novel drug delivery systems.

Acknowledgments

One of the authors Mr. Southward. Lankalapalli is thankful to the Council of Scientific and Industrial Inquiry (CSIR), India for the accolade of Senior Enquiry Fellowship to carryout the research work.

Footnotes

Lankalapalli and Kolapalli: Polyelectrolyte Complexes and Drug Delivery Technology

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866337/

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