Nanoparticles represent drug delivery systems suitable for most administration routes. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA), Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively investigated because of their biocompatibility and biodegradability. Nanoparticles act as potential carries for several classes of drugs such as anticancer agents, antihypertensive agents, immunomodulators, and hormones; and macromolecules such as nucleic acids, proteins, peptides, and antibodies. The options available for preparation have increased with advances in traditional methods, and many novel techniques for preparation of drug-loaded nanoparticles are being developed and refined. The various methods used for preparation of nanoparticles with their advantages and limitations have been discussed. The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants. Nanoparticles can be designed for the site-specific delivery of drugs. The targeting capability of nanoparticles is influenced by particle size, surface charge, surface modification, and hydrophobicity. Finally, the performance of nanoparticles in vivo is influenced by morphological characteristics, surface chemistry, and molecular weight. Careful design of these delivery systems with respect to target and route of administration may solve some of the problems faced by new classes of active molecules.

Encapsulation of biomacromolecules in polyester micro- and nano-particles is now a routine procedure in many laboratories for achieving controlled and targeted delivery strategies. Objectives: Proteins are notoriously difficult to encapsulate without some degree of unfolding and loss of bioactivity, and this is despite around two decades of research. A case by case analysis appears necessary when determining which mechanism, generally unfolding at the emulsion interface or acidification of the particle interior, is most detrimental. The transient nature of the emulsion systems makes in situ, real-time analysis of interfacial events difficult, necessitating interpretation from model interfacial systems or analysis post-fabrication. The review will focus on: i) the emulsification efficiency of proteins, cf. interfacial adsorption; ii) current excipients and techniques used to stabilise proteins, outlining work towards the oral delivery of insulin as a case study; iii) analytical techniques used to characterise encapsulated protein. There appears to be a recent trend towards the stabilization of proteins via direct complexation with polymers but, in contrast, emulsion techniques are emerging which err away from the use of stabilisers and/or excipients. A number of spectroscopic and spectrometric methods have found new application to the study of protein integrity in microspheres