A Review on Polymeric Nanoparticles

 

Ch. Prabhakar1 and K. Bala Krishna2*

1Dept. of Pharmaceutics, Chilkur Balaji College of Pharmacy, Aziz Nagar, Moinabad Road, Hyderabad, AP-500075

.               2Nova College of Pharmacy, Vegavaram, West Godavari District, AP

*Corresponding Author E-mail: balutundurru.balu5@gmail.com

 

ABSTRACT:

Polymeric nanoparticles are colloidal solid particles with a size range of 10 to 1000nm and they can be spherical, branched or shell structures made from biodegradable and non-biodegradable polymers, in which drugs are incorporated into nanoparticles by dissolution, entrapment, adsorption and attachment or by encapsulation. The choice of polymer and the ability to modify drug release from polymeric nanoparticles have made them ideal candidates for cancer therapy, delivery of vaccines, contraceptives and delivery of targeted antibiotics. In this review some of the polymers used in synthesis of polymeric nanoparticles and their applications were discussed.

 

KEYWORDS: Drug Delivery System, Polymer-Drug, Biodegradable polymers, Nanoparticles.

 


INTRODUCTION:

Use of polymeric nanoparticles is one of the most interesting approaches to achieving local controlled drug delivery. Polymeric nanoparticles are colloidal solid particles with a size range of 10 to 1000nm and they can be spherical, branched or shell structures made from biodegradable and non-biodegradable polymers, in which drugs are incorporated into nanoparticles by dissolution, entrapment, adsorption and attachment or by encapsulation1. Polymeric nanoparticles represent a significant improvement over traditional oral and intravenous methods of administration in terms of efficiency and effectiveness. Polymeric nanoparticles can be easily incorporated into other activities related to drug delivery, such as tissue engineering, and into drug delivery for species other than humans. The choice of polymer and the ability to modify drug release from polymeric nanoparticles have made them ideal candidates for cancer therapy, delivery of vaccines, contraceptives and delivery of targeted antibiotics2.The polymers that seem to have the best potential for this application are poly (lactide-co-glycolide) (PLGA), poly (alkylcyanoacrylate) (PACA), and poly(β-caprolactone) (PCL)3.These polymers have been studied for their applications or interactions with the eye and are found to have good biocompatibility4. Among the biodegradable and biocompatible polymeric carriers, nanoparticulate systems are interesting for controlled drug delivery and drug targeting.

 

These polymeric nanoparticles have been investigated especially in drug delivery for drug targeting because of their particle size (ranging from 10 to 1000 nm) and long circulation in blood5. Carrier size under 1 µm, an intravenous (i.v) injection (the diameter of the smallest blood capillaries is 4 µm) is enabled, minimizing any possible irritant reactions6. Polymeric nanoparticles made from natural and synthetic polymers have received the majority of attention due to higher stability and the opportunity for further surface nanoengineering. They can be tailor-made to achieve both controlled drug release and disease specific localization by tuning the polymer characteristics and surface chemistry7. Regarding the use of polymers in the field of pharmaceutical formulation the bio-safety and biocompatibility are the important characteristics needed. A proper consideration of surface and bulk properties can aid in the designing of polymers for various drug-delivery applications8.Biodegradable polymers find widespread use in drug delivery as they can be degraded to nontoxic monomers inside the body9.Polymeric materials used for the formulation of nanoparticles include synthetic poly(lactic acids) (PLA), poly(lactic-coglycolic acids) (PLGA), poly(ε-caprolactone) (PCL), poly(methyl methacrylates), and poly(alkyl cyanoacrylates) or natural polymers (albumin, gelatin, alginate, collagen or chitosan). Polyesters, alone and in combination with other polymers, are the most commonly used for the formulation of nanoparticles. PLGA and PLA are highly biocompatible and biodegradable. They have been employed since the eighty's for numerous in vivo applications (biodegradable implants, controlled drug release)10.

 

Poly(Lactic-Co-Glycolic Acid) :

PLGA or poly(lactic-co-glycolic acid) is a copolymer which is used in a host of Food and Drug Administration (FDA) approved therapeutic devices, owing to its biodegradability and biocompatibility. PLGA is synthesized by means of random ring-opening co-polymerization of two different monomers, the cyclic dimers (1,4-dioxane-2,5-diones) of glycolic acid and lactic acid. Common catalysts used in the preparation of this polymer include tin(II) 2-ethylhexanoate, tin(II) alkoxides, or aluminum isopropoxide. PLGA has been successful as a biodegradable polymer because it undergoes hydrolysis in the body to produce the original monomers, lactic acid and glycolic acid. PLGA a common choice in the production of a variety of biomedical devices such as: grafts, sutures, implants, prosthetic devices, micro and nanoparticles11. It has also been used successfully in delivery of amoxicillin in treating listeriosis (treatment of Listeria monocytogenes infection) as an example, a commercially available drug delivery device using PLGA is Lupron Depot for the treatment of advanced prostate cancer. The use of biodegradable polymeric NPs for drug delivery has been gaining momentum and shown significant therapeutic potential. Biodegradable polymers such as poly(D,L-lactic acid), poly(D,L-lactic-co-glycolic acid) and poly(3-caprolactone) and their co-polymers diblocked or multiblocked with PEG have been commonly used to form core–shell structured NPs to encapsulate a variety of therapeutic compounds12. PLGA has biodegradablenature and ability to encapsulate high amounts of hydrophobicdrugs13. Poly (L-lactic-co-glycolic acid) (PLGA) and its related components are among the most widely investigated degradable polymers in biomedical applications. The most extensive work with PLGA regarding material-brain research has been in controlled drug-release applications in the form of microspheres injected into the brain. PLGA has been generally accepted as biocompatible in that capacity14. PLGA have been used extensively for biomedical applications15.

 

Polycaprolactone:

Polycaprolactone (PCL) is a biodegradable polyester with a low melting point of around 60°C and a glass transition temperature of about −60°C. PCL is prepared by ring opening polymerization of ε-caprolactone using a catalyst such as stannous octanoate. The most common use of polycaprolactone is in the manufacture of specialty polyurethanes. PCL is degraded by hydrolysis of its ester linkages in physiological conditions and has therefore received a great deal of attention for use as an implantable biomaterial. In particular it is especially interesting for the preparation of long term implantable devices, owing to its degradation which is even slower than that of polylactide. In odontology or dentistry, it is used in root canal filling. Poly(e-caprolactone) (PCL) has also been studied in the brain for controlled-release microspheres, although not as extensively as PLGA. PCL has been most commonly studied in other tissue types and has a history of drug delivery and tissue-engineering research elsewhere in the body. Central nervous system (CNS) inflammation has also been studied in the context of electrode implants, where close contact of neuronal activity is desired16. PCL is a semi-crystalline, bioresorbable polymer belonging to the aliphatic polyester family. PCL is known to have a very slow degradation rate of up to 4 years in certain conditions17. Poly(ε-caprolactone) (PCL) obtained by ring opening polymerisation of ε- caprolactone was first reported by Pitt et al. for the controlled release of steroids and narcotic antagonists as well as to deliver opthalmic agents. PCL,aliphatic polyester has been intensively investigated as a biomedical material. The rate of biodegradation for PCL is slower than other biodegradable materials thus making it suitable for design of long term implantable systems. For example, Capronor, a US FDA approved contraceptive device18. Lemarchand et al have reported synthesis of amphiphilic copolymer based on Dextran grafted with PCL chains which significantly reduced protein absorption19.

 

Poly(Alkyl Cyanoacrylate)

Nanoparticles based onbiodegradable poly(alkyl cyanoacrylate) (PACA) may be considered today as an establishedtechnology for colloidal nanomedicine.PACA drug carriers have demonstrated significant results in numerous pathologies such as cancer, severe infections (viral, bacteriologic, parasite) as well as several metabolic and autoimmune diseases20. Coating nanoparticles with poly(ethylene glycol) (PEG),allows them to escape the recognition process by the macrophages of the mononuclear phagocyte system, resulting in long-circulating colloidal devices, also called “stealth” nanoparticles21. Among suitable nanocarriers for drug delivery purposes, nanoparticles based on biodegradable poly(alkyl cyanoacrylate) (PACA) (co)polymers have appeared as an established technology for colloidal nanomedicine22. Vauthier et al demonstrated the potential of poly (alkylcyanoacrylate) (PACA) NPs to overcome multidrug resistance problems at cellular level and in relation to drug biodistribution. Resistant cells treated with doxorubicinloaded poly (alkyl cyanoacrylate) nanoparticles showed a much higher sensitivity to the drug, relative to the free drug when compared with NPs using other biodegradable polymers23.

 

Eudragit Retard Polymer

Use of polymeric nanoparticles is one of the most interesting approaches to achieving local controlled drug delivery. In this field, Eudragit Retard polymer nanoparticle suspensions have been investigated as a carrier system for the ophthalmic release of nonsteroidal antiinflammatory drugs, such as ibuprofen and flurbiprofen. Polymeric nanosuspensions, prepared from Eudragit® RL 100 and RS 100, have been investigated extensively for the ocular delivery of ibuprofen, flurbiprofen, cloriocromene, piroxicam, methyl prednisolone, and amphotericin B24. Use of polymeric nanoparticles is one of the most interesting approaches to achieving local controlled drug delivery. Polymer nanosuspensions (NS) of nonsteroidal anti-inflammatory agents (NSAIDs) have often been proposed as controlled drug delivery systems able to solve pharmacokinetic problems and/or the gastric damaging effects typical of most of these drugs25.

Application of Polymeric Nanoparticles in Drug Delivery Systems:

·          Association of anticancer drugs or cytotoxic agents with nanoparticles has resulted in efficient drug penetration, cell internalization, controlled release, and reversion of multidrug resistance and protection from premature inactivation during transport, reduction of toxicity to healthy cells or tissues.

·          Nanoparticles are utilized as drug delivery vehicles to deliver drugs and therapeutic peptides across the blood brain barrier to treat brain tumors, Alzheimers disease, prion disease and other neurological disorders.

·          Pulmonary delivery of drugs and biotherapeutics including Insulin contained within nanoparticles are attractive for noninvasive and sustained targeted delivery for both local and systemic application. Most commonly chitosan, alginate and PLGA are the nanocarrier materials used for pulmonary delivery of Insulin, antitubercular drugs and antifungal drugs.

·          Nanoparticulate drug delivery systems have been investigated as a novel approach to enhance ocular availability of drugs and therapeutic agents.

·          Sustained release of DNA from nanoparticles intracellularly would be effective in achieving gene expression to the target tissue in conditions such as cardiac and limb ischeamia, angiogenesis and bone regeneration 26.

·          Chitosan NP internalization was found to be higher in the jejunum and ileum than in duodenum (Behrens et al., 2002).

·          Among the polymers used to form vaccine nanoparticles, chitosan is one of the most recently explored and extensively studied as prospective vaccine carriers (Illum et al., 2001; van der Lubben et al., 2001).

·          Doxorubicin loaded chitosan NP showed regression in tumor growth and enhance survival rate of tumor-implanted rats after IV administration27.

 

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Received on 19.12.2010          Modified on 03.01.2011

Accepted on 19.01.2011         © RJPT All right reserved

Research J. Pharm. and Tech. 4(4): April 2011; Page 496-498