Parenteral drug delivery nanoparticles

Wissing SA, Kayser O, Muller RH. Solid Upid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 2004, 7 May 56(9) 1257-1272. 

Wissing, S., Kayser, O. and Muller, R.H. (2004) Solid lipid nanoparticles for parenteral drug delivery. Adv. Drug. Deliv. Rev., 56, 1257-1272. 

Solid lipid nanoparticles were originally developed for parenteral drug delivery to provide a parenteral drug carrier system based on physiological compounds and a potential controlled release and/or targeting of the drug. A broad variety of drugs (e.g. doxorubicin, camptothecin, etoposide, mitoxan-trone, tamoxifen,paclitaxel, clozapine, lovastatin, bromocriptine, temozolomide, actarit and dexametha-sone °) has already been incorporated into SLN formulations and tested in vivo in mice or rat. 

Compared to lyotropic LCNP the thermotropic mesophase-based supercooled smectic nanoparticles are in a still much more early stage of development. Although structural aspects of these nanoparticles are not quite as complex as with lyotropic LCNP and the physicochemical properties of these nanoparticles as well as the influencing parameters on the phase behavior have been studied in some detail yet much remains to be done for further optimization of the formulations in particular with regard to the stability of the nanoparticles against recrystallization. Furthermore, application related studies have to be performed, especially with a focus on parenteral drug delivery which was the main driving force for the development of these particles. 

M El-Samaligy, P Rohdewald. Triamcinolone diacetate nanoparticles, a sustained release drug delivery system suitable for parenteral administration. Pharm Acta Helv 57 201, 1982. 

Parenteral is defined as situated or occurring outside the intestine, and especially introduced otherwise than by way of the intestines —pertaining to essentially any administration route other than enteral. This field is obviously too broad for an adequate focus in one book, let alone one chapter. Many have nonetheless used the term synonymously with injectable drug delivery. We restrict ourselves to this latter usage. This would thus include intravenous, intramuscular, subcutaneous, intrathecal, and subdural injection. In this chapter we discuss the theoretical and practical aspects of solubilizing small molecules for injectable formulation development and will examine the role of surfactants and other excipients in more recent parenteral delivery systems such as liposomes, solid-drug nanoparticles and particulate carriers. 

Apart from the already established formulations, researchers are trying to develop novel oil-based formulations to combat the poor solubility and bioavailablity of NCE. Shevachman et al. developed novel U-type microemulsions to improve the percutaneous permeability of diclofenac. Shah et al.2 2 used microwave heating for the preparation of solid lipid nanoparticles by microemulsion techniques, which resulted in improved particle characteristics. Ki et al. reported sustained-release liquid crystal of injectable leuprolide using sorbitan monooleate. Recently, various novel oil-based drug delivery technologies are reported, which includes tocol emulsions, solid lipid nanopar-ticles, nanosuspensions, Upid microbubbles, sterically stabilized phospholipid micelles, and environmentally responsive drug delivery systems for parenteral administration.25 259... 

Parenteral administration (injection), which is the immediate option for orally undeliverable drugs, has advanced greatly in recent years for systemic and local drug delivery. " The novel drug delivery system has metamorphosed from simple polymer and antibody conjugates to sterically stabilized colloidal systems. Liposomes and nanoparticles can improve pharmacokinetic-pharmacody-... 

Apart from oral drug delivery, the drug nanoparticles might have a large potential in pulmonary delivery but also in parenteral dosage forms, in particular, the fad that some nanosuspensions may behave like solutions regarding their pharmacokinetics (3) appears to be a very interesting feature. 

The broad diversity of SLN formulations for drug delivery is illustrated in the background of selected publications of SLN formulations for, e.g. the parenteral, oral and dermal administration particularly with respect to the in vivo fate of the lipid nanoparticles and incorporated drugs. 

Solid lipid nanoparticles have been investigated in many different administration routes parenteral, oral, (trans)dermal, ocular d64,i97 pulmonary.Furthermore, cationic SLN formulations were used to complex DNA for cell transfection. In the following chapter, selected studies are summarized with respect to a parenteral, oral and dermal administration as well as for gene delivery to illustrate the versatility of solid lipid nanoparticle formulations in drug delivery. 

J.E. Kipp, The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs, Int. J. Pharm., 284, 109-122 (2004). 

Besides parenteral application of microspheres and nanoparticles for cell selective delivery of drugs, they have more recently been studied for their application in oral delivery of peptides and peptidomimetics [30]. Immunological tolerance induction against beta-lac-toglobulin could be achieved by application of this protein in a poly-lactic-glycolide microsphere formulation [31]. 

Surfactants are employed in nanoparticle suspensions. Chen et al. (2002) evaluated the pre paration of amorphous nanoparticle suspensions containing cyclosporine A using the evaporative precipitation into aqueous solution (ERAS) system. The effect of particle size was studied varying the drug surfactant ratios, type of surfactants, temperature, drug load, and solvent. Acceptable particle sizes suitable for both oral and parenteral administration were also studied. Additional articles in the nanoparticle delivery of poorly water-soluble drugs include Kipp (2004), Perkins et al. (2000), Young et al. (2000), and Tyner et al. (2004). 

Technological advances in both biotechnology and molecular biology have yielded a surge in the number of new chemical entities that are produced to treat specific diseases or ailments. However, a growing portion of these new chemical entities display poor aqueous solubility, leading to poor oral bioavailability and an inability to form intravenous formulations. Nanoparticle formation has been proposed and utilized as a method to improve oral bioavailability of poorly soluble drugs and as a method for delivery of particles via parenteral, pulmonary, and topical administration. 

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