Abstract: Polymer selection in formulation plays a important role in different dosage forms because drugs in various concentration, transport system its rate of mechanism, drug release depends on polymer used. Polymer used may be beneficial or harmful various methods detect mechanism or rate of drug release. This article explains various polymers used with drug transport systems and importance of polymers.
Polymers have numerous advantages in drug delivery technology also act as inert carrier, improves pharmacokinetic and pharmacodynamic properties. There are basically two types of polymers natural which are abundant biodegradable and synthetic which have high immunogenicity in which naturally occurring such as guar gum, pectin, cyclodextrin, dextran, amalyase, chitosan, chondrotin sulphate, locust bean gum. Synthetic polymers such as shellac, ethyl cellulose, cellulose acetate phthalate, hydroxyl propyl methyl cellulose, eudragit, polyvinyl acetate phthalate.
Synthetic polymers:
Synthetic polymers used in various transport systems has revealed previously. Several polymers of PEG such as polyethylene glycol, polyethylene glycol based detergent, others like poloxamers, dentrimers, and thiomers, played a important role in various formulations and has been investigated for the efflux pump inhibitory activity.
Polyethylene glycol and its derivatives PEG 400 (5% w/v) restrict digoxin transport in secretory direction and on other side restriction found regardless by addition of PEG 400 which was concluded decreased P-gp activity at apical side was studied by Johnson et al. PEG 400 have indirect effect in efflux restriction of digoxin which proved the effect of PEG on P-gp activity to illustrate interaction between PEG 200,300,400 using caco-2 cell monolayer’s was studied by Ashiru-Oredope et al. Ranitidine increased flux permeable with PEG 300,400 with P-gp transporters but this not shown with PEG 200.
Thiolated poly (acrylic acid)-250,thiolated PAA 250 (effect of thiolated polymer) using MRP2 substrate suforhodamine 101 explore more absorption from gut compared with thiolated PAA 250 and unthiolated PAA 250 thus indicates restrict action of MRP2 which was highest in duodenum this overall study i.e. invivo and invitro was done on rat intestinal mucosa. Dipyridamole restrict P-gp activity which increased digoxin absorption and plasma level investigated on rat, the third generation inhibitor OC114-093(ONT-093) used for oral uptake of docetaxel.
Polyethylene glycol, pluronics, tween 80, tween 20, thiomers vitamin E derivatives are used as polymeric P-gp inhibitors in oral bioavailability. Doxorubicin and PEG 300 restrict efflux transporters of P-gp activity in Caco-2 monolayers. Polyacrylic acid and pluronic P investigated cell absorption of doxorubicin restricting by P-gp activity in Caco-2 monolayers. Copolymers poly 2-hydroxyethyl methacrylate-co-methyl (P-HEMA-co-MMA) were used to study swelling and relaxation behavior in experiments by Davidson and Peppas. All types of orally taken anticancer drugs found to be excreted by first metabolic process with cytochrome P450 and P-gp.
It was concluded that vitamin E TPGS boost oral bioavailability of cyclosporine which is also a reversal agent of P-glycoprotein restricts activity thus P-gp or P-450 suppressors which decrease immune system in patients which was studied in healthy dogs. Amprenavir increases solubility, permeable which is a HIV protease inhibitor embellishes absorption when it interacted with Vitamin E TPGS agent. It was concluded that NSVs are safe have a ability to enter Caco-2 cell monolayer various transport system like intracellular uptake results PEGylated nanoparticles have no effect on Caco-2 cell monolayer which activates transcytosis pathway. Results demonstrated polyethylene oxide chains interact with bioadhesive properties of NSVs which can also pass through monolayer proved to increase transport systems across intestinal epithelial barrier. NSVs proved to be beneficial in patient compliance also as a innovative and promising nanocarrier for oral administration. (a)
Drug loaded conjugates in cellular transport studies when compared with drug solution and other co cultured cell, both P-gylcoprotein and multiple resistance protein-2 showed greater drug conjugates capability in transport systems. (c)
Study was reported on placenta which demonstrated P-gp activity with quinidine or chlorpromazine which increased transplacental clearance of CsA, also rhodamine 123 effect on P-gp activity does not limit entry inside the circulation but also eliminates substrates. The direct effect of drugs is avoided by P-gp which protects fetus also many other dyes like saquinavir, methadone, indinavir, prazosin, rhodamine 123 have direct effect of P-gp substrates.( d)
Several concentrations of tween 80 (0.1-1% v/v) stated inhibitory effects on P-gp ATPase which is used in characterizing compounds as substrates/inhibitors/stimulators gives a great approach in development and delivery of P-gp.(E)
Paclitaxel and doxorubicin restrict cytochrome P450 mediated clearance of anticancer agents. Several modulators demonstrated by various studies as ex vivo with rhodamine in CD56+,overall many factors are responsible for dosing like higher potency, selectivity, surrogate endpoints which is required in development of drugs. (g)
Invitro studies stated 2 fold and 4 fold reduction of ofloxacin by DNP (proton motive force inhibitor) and verapmil (calcium channel blocker for ABC transporters) and piperine respectively which gives synergistic effect at 12.5µg/ml on efflux pump inhibitor for M.tuberculosis. It was reported that piperine has a ability to interact with DNA and protein. Anti tuberculosis drugs showed reversal action for efflux pump inhibitors CCCP and verapamil. Piperine showed inhibited action towards efflux pump of mycobacteria which increased drug uptake across cell also increase the membrane permeability. (h)
ABC transporters such P-gp, MRP2, and BCRP helped to study various diseases such as epilepsy and other pharmacological activities are specially modified to enter blood brain barrier novel tools developed of specific transport inhibitors, antibodies, interactions facilitate drug transport in brain with ABC transporters.(f)
Study investigated of thiolated polymer which increase CS-N-Arg and THL-fucoidan nanoparticles showed increasing effect on water soluble molecule dextran and water insoluble p-glycoprotein substrates like rhodamine 123.These nanoparticles showed permeability by cationic CS-N-Arg and restricting path of protein tyrosine phosphate and P-glycoprotein.by thiolated polymer.
Polymers used in formulation play a vital role as it impacts final dosage form which proved beneficial or dangerous also physiochemical and biological properties effect drug bioavailability hence it is important to choose effective polymer to gain highest bioavailability in formulation.
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