Biodegradable polymeric nanoparticles as drug delivery devices

Abstract

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

Introduction

Over the past few decades, there has been considerable interest in developing biodegradable nanoparticles (NPs) as effective drug delivery devices. Various polymers have been used in drug delivery research as they can effectively deliver the drug to a target site and thus increase the therapeutic benefit, while minimizing side effects [1]. The controlled release (CR) of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing such devices. Liposomes have been used as potential drug carriers instead of conventional dosage forms because of their unique advantages which include ability to protect drugs from degradation, target the drug to the site of action and reduce the toxicity or side effects [2]. However, developmental work on liposomes has been limited due to inherent problems such as low encapsulation efficiency, rapid leakage of water-soluble drug in the presence of blood components and poor storage stability. On the other hand, polymeric NPs offer some specific advantages over liposomes. For instance, NPs help to increase the stability of drugs/proteins and possess useful CR properties.

Nanoparticles generally vary in size from 10 to 1000 nm. The drug is dissolved, entrapped, encapsulated or attached to a NP matrix and depending upon the method of preparation, nanoparticles, nanospheres or nanocapsules can be obtained. Nanocapsules are vesicular systems in which the drug is confined to a cavity surrounded by a unique polymer membrane, while nanospheres are matrix systems in which the drug is physically and uniformly dispersed. In recent years, biodegradable polymeric NPs have attracted considerable attention as potential drug delivery devices in view of their applications in the CR of drugs, their ability to target particular organs/tissues, as carriers of DNA in gene therapy, and in their ability to deliver proteins, peptides and genes through a peroral route of administration [3], [4].

Some general aspects on micro- and nanoparticles have been reviewed earlier [1], [5], [6], [7], [8], [9], [10], [11]. A majority of these reviews have dealt with the NPs of poly(d,l-lactide), poly(lactic acid) PLA, poly(d,l-glycolide) PLG, poly(lactide-co-glycolide), PLGA, and poly(cyanoacrylate) PCA. The present review details the latest developments on the above mentioned polymers as well as NPs based on chitosan, gelatin, sodium alginate and other hydrophilic/biodegradable polymers. Surface modification aspects are also covered in more detail. The PLA, PLG and PLGA polymers being tissue-compatible have been used earlier as CR formulations in parentral and implantation drug delivery applications [12], [13], [14]. In addition, poly(ϵ-caprolactone), PCL, which was first reported by Pitt et al. [15], [16] for the CR of steroids and narcotic antagonists as well as to deliver opthalmic drugs [17], and poly(alkylcyanoacrylate), PACA, are now being developed as NPs. In addition, less frequently used polymers like poly(methylidene malonate) [18], gelatin [19], chitosan [20] and sodium alginate [21] will also be included in this review. The important published literature within the period 1990–2000 is critically reviewed. The review does not cover the entire literature within this period, but the reader is advised to go to the original literature in order to get more details.