Keyur Vasava
Introduction:
The convetional manner of introducing drug to patient is inefficient and often lead to toxic side effect The dramatic advance in controlled and targeted drug delivery system over past few decades have lead to enormous expectation for treatment of no of complicated aliments with minimum side effect. One class of such system is intelligent drug delivery system. Intelligent drug delivery systems are capable of adjusting drug release rates in response to a physiological need. This system help to maintain drug in therapeutic range with single, localize delivery of drug to particular compartment, preserve the medicament that are rapidly destroyed ,improved patient compliance. Intelligent drug delivery system may be open- loop system or closed-loop systems.
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Urea-responsive drug delivery system Inflammation-induced pulsatile release Morphine triggred naltrexone delivery system System utilizing antibobody interaction System utilizing chelation
Pulsatile system :
PDDS(pulsatile drug delivery systems) are gaining importance in the field of pharmaceutical technology as these systems deliver the right dose at specific time at a specific site. Some of the disease conditions wherein PDDS are promising include duodenal ulcer, cardiovascular diseases, arthritis, asthma, diabetes, neurological disorder, cancer, hypertension and hypercholesterolemia. In pulsatile drug delivery system drug release is programmed by external stimuli like magnetism, ultrasound, electrical effect and irradiation etc.
Electrically responsive delivery systems are prepared from polyelectrolytes (polymers which contain relatively high concentration of ionisable groups along the backbone chain) and are thus, pH-responsive as well as electro-responsiv. In this system drug is disperse in hydrogel which is implanted subcutaneously. When drug release is desired, an electroconducting patch is applied on skin directly over gel.and electrode are pluuged into patch and electrical field is applied on skin. Under influence of electrical field, electroresponsive hydrogel Deswell or bend and releassse the drug. Also hydrogel in the form of beads can be injected subcuteneously or polymer solution which can be injected as liquid but which form gel at body temparature. Electrical current is also use in form of iontophoresis or electroporation in field of transdermal drug delivery. Examples of naturally occurring polymers include hyaluronic acid, chondroitin sulphate, agarose, carbomer, xanthan gum and calcium alginate. The synthetic polymers are generally acrylate and methacrylate derivatives such as partially hydrolyzed polyacrylamide, polydimethylaminopropyl acrylamide
Ultrasonically modulated system: In this system release rate of drug is repeatedly modulated externally by ultrasound. Both non erodible as well as bioerodible polymer are used for preparation of polymer
matrices.
Bioerodible
polymers include polyactide, polyglycolide, carboxyphenoxy)alkane anhydridesand their copolymers with sebacic acid.
poly(bis(p-
The bioactive used are p- aminohippurate, , insulin and bovin serum albumin etc. On exposure to ultrasound, polymer erosion occur and drug is release in controlled
manner from polymer metrices.
While in the non erodible polymer system, drug release is diffusion controlled. Studies revealed that that release rate of bovine serum insulin from ethylene vinyl acetate
copolymer matrices were 15 time higher when exposed to ultrasound.
It has been found that extent of enhancement can be regulated by the frequency, intensity,
or or cycle of applied ultrasound.
Photoresponsive system:
This approach involves use of photoresponsive polymer. The photoresponsive polymer consist of photoreceptor usually photochromic chromophore and functional part. Photoresponsive system is triggered by light stimulus
leading to macroscopic changes in the system for controlled release of drug in terms of quantity, location and time. The Photoresponsive system is a molecular scale polymer matrix of photolabile conjugates with drug, which can be exposed to light stimuli with high level of control in terms of wavelength, duration, intensity and location; leading to photo-chemical reaction yielding deformation of conjugates and drug liberation from matrix. Light-sensitive conjugates are synthesized by Dicyclohexylcarbodiimide mediated method or Direct acid chloride esterification method. Incorporation of the conjugates into limitedporosity hydrogels like hydrated copolymer of 2-(hydroxyethyl) methacrylate and methyl methacrylate which are crosslinked with ethylene glycol dimethacrylate, leading to formulation of molecular level dosing devices. 3, 5 - dimethoxybenzoin is one of such photolabile conjugate which can be precisely and kinetically controlled to liberate free drug following exposure of 365 nm light for definite time period. Photoresponsive system has found applications in the ophthalmology (Intra ocular lenses for cataract treatment) as well as in administration of NSAIDS. Low energy radiation and accurate control on applied light by sophisticated equipment are the unique features of the system. The synthesis of novel photolabile conjugates and incorporation of more drugs in the Photoresponsive system may enhance patient compliance by reduction in side effect and promote the scientific research towards precisely controlled drug delivery
2. Responsive system :
Polymers responsive to change in their environment are of research interest. Many research groups are engaged in developing delivery system based on these responsive polymer. In this system drug delivery is controlled by means of an interaction with the surrounding environment without the aid of any external agency.
Tissue/cellular compartment Blood Stomach Small intestine Colon Lysosome Golgi Tumour, extracellular
Polymer
Poly (N,N-diethylacrylamide) Poly (methyl vinyl ether) Poly (N-vinylcaprolactam) PEO-b-PPO (b) Poly (GVGVP) Pluronics, tetronics, Poloxamer The temparature modulation of drug delivery can be employed in following condition: 1. Hyperpyrectic drugdelivery : The normal body temperature of 37 C is elevated by the physiological presence of pathogens and pyrogens. Thus self regulating or auto feedback drug delivery device can be designed that release antipyretic drug in response to inceased body temperature. 2. Transdermal delivery system Thermosensitive polymeric membrane can be used as an on off switches in transdermal devices to achieve pulsatile drug delivery from skin 3. Externally modulated devices: Drug delivery devices relying on external modulationfor drug releasecan be desiged to respond to external temperature, and monitor or mediate drug release according to therapeutic need
Kitano,1992, developed a glucose sensitive insulin delivery system based on a sol-gel transition. A phenyl boronic acid(PBA) moiety was incorporated in poly(N-vinyl-2pyrrolidone) using radical copolymerization of N-vinyl-pyrrolidone with m-acrylamido phenyl boronic acid[poly(NVP-Co-PBA)]. Insulin was entrapped into the polymer gel formed by a complex of poly(vinyl alcohol) withpoly(NVP-co-PBa). PBA forms reversible Covalent complexes with molecules having diolunits, like PVA or glucose. When glucose is added, PVA from the PVA-bromate complex is replaced by glucose. This leads to the transformation of the system from gel to sol state facilitates the releas of insulin from the polymeric complex
Urea-responsive delivery
Heller and Trescony were the first to attempt using immobilized enzymes to alter local pH and thus cause changes in polymer erosion rates. The proposed system is based on the conversion of urea to NHaHCO3 and NHaOH by the actionof urease. As this reaction causes a pH increase, a polymer that is subjected to increased erosion at high pH is required. The authors suggested a partially esterifled copolymer of methylvinylether and maleic anhydride. This polymer displays release rates that are pH dependent. The polymer dissolves by ionization of the carboxylic acid group. Release of hydrocortisone from a disk composed of N-hexyl half ester of methylvinylether and maleic anhydride surrounded by a hydrogel containing urease immobilized by glutaraldehyde crosslinking. Although the device has no therapeutic relevance, it established the feasibility of creating self-responsive delivery system.
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In presence of specific metal iona complexing with bound chelating agent will takeplace, followed by metal accelerated hydrolysis and subsequent elimination of metal chelate.
Delivery system for metal chelators, based on metal promoted hydrolysis of carboxylic esters.
References :
Vyas S.P. And Khar Roop K., Controlled Drug Delivery Concepts and Advances; Vallabh Prakashan, Delhi. Page no. 36-44 Joseph Kost and Robert Langer, Advanced Drug Delivery Reviews, 6 (1991) page no. 1950
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