Recent updates in synthetic polymers used in drug delivery systemsPresentation Transcript
Recent updates in synthetic polymers used in drug delivery systems KUSUM SINGH NEELAM SINGH I.T.S. PHARMACY COLLEGE,GHAZIABAD, INDIA
PROPERTIES & SELECTION OF SYNTHETIC POLYMERS
SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS
Significant advances have been made in development of various drug delivery devices with the help of polymers.
The earliest DDS first introduced in 1970s were based on polymers formed from lactic acid.
Today polymeric materials still provides most important avenues of research primarily because of ease of processing & ability of researchers to readily control their chemical & physical properties via. Molecular system.
Compounds with high molecular masses formed by combination of large number of simple molecules called as monomers.
Prepared by addition / condensation polymerization.
In Greek , Poly means many & meros means units/parts.
Polymers are of 3 types:-
Natural, Semisynthetic, Synthetic.
CLASSIFICATION OF SYNTHETIC POLYMERS ON THE BASIS OF STRUCTURE BRANCHED CHAIN POLYMERS EXAMPLES :- Low Density Polythene CROSS LINKED POLYMERS EXAMPLES:- Bakelite, MF Resin LINEAR POYMERS EXAMPLES :- PEG, Polyesters
CONTD… ON THE BASIS OF DEGRADABILITY OF POLYMERS BIODEGRADABLE POLYMERS NONBIODEGRADABLE POLYMERS ENVIRONMENT RESPONSIVE POLYMERS ELECTRICALLY & CHEMICALLY CONTROLLED POLYMERS THERMOSENSITIVE POLYMERS pH-SENSITIVE POLYMERS
BIOADHESIVE POLYMERS IN MUCOADHESIVE DRUG DELIVERY SYSTEMS BIOADHESIVE PROPERTIES CHARACTERISTICS Poly-hydroxyl Butyrate Poly(e-caprolactone) Polyorthoesters Polyphosphazenes Polycyanoacrylates Polyvinyl Acetate Polyethyleneoxide-b-propylene oxide Biodegradable Properties can be changed by chemical modification Surface eroding polymer Can be tailored with versatile side chain functioning Biodegradable Biocompatible Amphiphillic surfactant Biocompatible Matrix for DDS Cell encapsulation Sustained DDS, opthalmology To make films, Hydrogels in DDS Surgical adhesives, glues in DDS Gels & Blended membranes in DD & Immobilization Protein delivery
SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS
Sustained Release DDS follows 1 st order release kinetics.
Increased crosslinking of polymers decreases diffusion rate & thus improves sustained release properties of polymers & decreases mucoadhesivity.
Synthetic Absorbable Polymers- include homopolymers like PLA, PGA, PCL, Polytrimethylene carbonate, Poly(p-dioxanone) & copolymers like- Poly lactide-co-glycolide, Poly (glycolide-co-trimethylene carbonate).
SYNTHETIC POLYMER APPLICABILITY Poly(Monosteroyl Glycerol-co-succinate) For Sustained release of Theophylline/ Risperidone from microparticles in-vitro Polyvinyl Acetate For sustained release capsules of Nifedipine Eudragit RLPM, RSPM & HPMC Sustained release of theophylline
Poly-L-lysine :- Biodegradable, lacks –NH 2 gp. with a pK a between 5 & 7 allowing no endosmolysis, resulting in low transgene expression.
This drawback requires inclusion of endosmolytic agent like Fusogenic peptide like –
Copolymer of Poly-L-lysine with Poly-L-histidine/ L-tryptophan.
Polyethyleneimine- Shows efficient transfecting ability without use of fusogenic agent.
PEI offers high charge density due to which it offers increased protection against serum nucleases.
SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS
Properties of synthetic Polymers considered for Opthalamic DDS-
Non-Toxic, Biodegradable, Biocompatible, Optically transparent, Do not impede vision, Tolerable, good retention properties, mucoadhesivity.
Non-Biodegradable polymeric bioadhesives used as drug delivery systems:-
Copolymers based on Vinylpyrrolidone, Methacrylic acid, Polydimethylene- siloxane, Poly (N-isopropyl acrylamide), PAMAM dendrimers.
CONTD… SYNTHETIC POLYMERS APPLICABILITY Polyhydroxy ethyl - methacrylate Used to formulate liposomes loaded with Dimyristoyl phosphatidylcholine (DMPC). It is optically transparent & release drug for a period of 8 days. Poly (D,L-lactide) Biodegradable polymer used for sustained retinal delivery of Celecoxib to inhibit diabetes induced Retinal oxidative demage Polyanhydrides, Polyorthoesters For sustained release of 5-FU Poly (Ɛ-caprolactone) rod shaped implants Tolerated by retinal tissues & used to release corticosteroid triamcinolone acetide over 4 weeks
SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM
Polymers are the backbone of TDDS.
TDDS are fabricated as multilayered polymeric laminates or drug- polymer matrix is sandwiched between two polymeric layers i.e. backing layer & inner polymeric layer which act as adhesive & Rate- controlling membrane.
TDDS is formulated either as Matrix form / Reservoir form.
IN TDDS POLYMERS ACTS AS MATRIX FORMERS BACKING LAYERS RELEASE LINERS RATE –CONTROLING MEMBRANE PRESSURE- SENSITIVE ADHESIVES (PSAs)
Selected on the basis of:-
Adhesion cohesion balance
e.g.-Monolithic solid state design is preffered for Passive TDDS
Synthetic polymers used-
Cross linked PEG network
Used for protein drug delivery.
b) Acrylic acid matrices
Acrylic acid + Plasticizer :- used to make drug- polymer matrix
Cationic block copolymer forms complex with Polyanionic biomolecules like
DNA & ODNs like PEO-b-Polyspermine which make complex with ODNs.
PEO-b-PPO triblock combination for Doxorubicin delivery.
Microscopic sac that encloses a volume with molecularly thin membrane. The membrane are self- directing assemblies of amphiphilic molecues with dual hydrophobic- hydrophobic characters.
SYNTHETIC POLYMER APPLICABILITY Non-ionic Polyethylene-oxide- Poly butadiene To form vesicles in aqueous solution PMOXA- PDMS- PMOXA Water soluble & midblock is hydrophilic (PEO- Polyethylethylene To form polymerosomes in aqueous solution for encapsulating Doxorubicin
SYNTHETIC POLYMERS USED IN
LIPOSOME DRUG DELIVERY SYSTEMS
Polymer properties to be considered :-
Improves liposomal stability.
Easy to associate with liposome surface.
A) pH-Sensitive Polymer –Liposome system
pH-sensitive synthetic polymers used:-
Poly-L-lysine & Poly (His) –
Positively charged at low Ph
Interact with negatively charged membranes & promotes fusogenic
PAMAM – Shows pH-dependent membrane destabilization & thus used for
cytoplasmic gene delivery.
Provide Temp-responsive properties.
POLYETHYLENE GLYCOL –
↑ Repulsive forces at surface & thus ↓ interaction & plasma protein
Amphipathic polymer with ABA Block structure.
Tetrafunctional Block copolymer with four PEO-PPO Blocks joined together
by central Ethylene diamine bridge.
[(PEO-PPO) 2 - X- (PPO-PEO) 2 ]
[(PEG-PPG) 2 - X- (PEG-PPG) 2 ]
Remington, “The Science & Practice of Pharmacy”
Volume- І , B.I. Publications Pvt. Ltd, Lippincott Williams & Wilkins company.
Lachman Leon, Lieberman HA, Kanig J.L, “The Theory & Practice of Industrial Pharmacy”, 3 rd edition, Varghese Publication.