Vaccine delivery: lipid-based delivery systems

Needle-free delivery of vaccines should not only increase compliance, but should also prove to be a safer and less traumatic method of vaccine delivery. One of the potential ways to achieve needle-free delivery is with the use of lipid-based delivery systems. To demonstrate the utility of these systems, we have shown them to be effective with proteins produced by recombinant DNA technology, plasmid-based vaccines, as well as conventional vaccines. Furthermore, these lipid-based delivery systems were shown to be effective in inducing mucosal immunity if delivered to mucosal surfaces or systemic immunity if different transdermally. These approaches have the potential to revolutionize vaccine delivery in humans and animals.     

Long-term vaginal antibody delivery: delivery systems and biodistribution

Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different (125)I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at approximately 100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was approximately 3 h; the half-life for IgG(1) clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was approximately 0.01 to 0.03 h(-1). These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels.     

Targeted delivery of doxorubicin: Drug delivery system based on PAMAM dendrimers

Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4°C and was absorbed by the cells at 37°C. The covalent binding to G2-FITC of a vector protein, a recombinant fragment of the human alpha-fetoprotein receptor-binding domain (rAFP3D), increased the binding and endocytosis efficiency more than threefold. Covalent conjugates of G2 with doxorubicin (Dox) obtained by acid-labile linking of cis-aconitic anhydride (CAA) without the vector protein (G2-Dox) and with the vector protein rAFP3D (rAFP3D-G2-Dox) were accumulated by the tumor cells with high efficiency. However, a selective effect was observed only in rAFP3D-G2-Dox, which also demonstrated high cytotoxic activity against the human ovarian adenocarcinoma SKOV3 cells and low cytotoxicity against human peripheral blood lymphocytes. Based on these results, rAFP3D-G2 conjugate is promising for selective delivery of antitumor drugs.     

Transdermal peptide delivery

The transdermal delivery of peptide drugs, though ill-favoured by their hydrophilicity and high molecular mass, would seem very attractive from the pharmacotherapeutical and patient compliance point of view. In some cases, effective transdermal dosing has been achieved in vivo, especially with the aid of iontophoresis. This paper deals with a dodecapeptide, des-enkephalin-gamma-endorphin, of which the transepidermal permeation and the intra(epi-)dermal biotransformation were both studied in vitro. Small, though measurable, fluxes through human stratum corneum were obtained in vitro, which could be enhanced by using a skin lipid fluidizer. The half-life of the peptide, both in the epidermis and in the dermis, was surprisingly long as compared with that in human plasma. Hence, improvement of the transdermal bioavailability of the peptide will most likely be obtained chiefly by enhancing its flux (possibly through iontophoresis), intra(epi-)dermal degradation being a problem of only minor importance.     

Intramolecular aglycon delivery

A Minireview with 51 references covering the two-step tethering and intramolecular glycosylation process termed intramolecular aglycon delivery (IAD). Specifically, glycosylation reactions where the tethered oxygen acts as nucleophile are covered. In the majority of cases, tethering to O-2 of a glycosyl donor ensures formation of a 1,2-cis glycoside after intramolecular glycosylation.     

Peptide delivery systems

Efficient delivery of peptide drugs to the desired site is very important. There are anumber of barriers that may limit using peptides as potential drugs, some of theseobstacles include poor biomembrane permeability, enzymatic degradation and lowpH. To improve peptide drug efficiency a selective drug delivery system is required.Here we review some of the delivery systems available for peptides and we will alsobriefly discuss peptides that have been used as delivery systems.     

Gene delivery platforms

One of the key challenges in the experimental and therapeutic use of gene delivery agents is the development of methods that can efficiently deliver nucleic acids into living systems. During the past decade, the development of effective and safe gene delivery systems has been intensively investigated. This review summarizes the current state of gene delivery methods based on viral and non-viral agents.     

Peptide delivery systems

Summary Efficient delivery of peptide drugs to the desired site is very important. There are a number of barriers that may limit using peptides as potential drugs, some of these obstacles include poor biomembrane permeability, enzymatic degradation and low pH. To improve peptide drug efficiency a selective drug delivery system is required. Here we review some of the delivery systems available for peptides and we will also briefly discuss peptides that have been used as delivery systems.     

Drug delivery.

Methods for the delivery of the products of biotechnology, namely peptides and proteins, are reviewed. More efficient methods of parenteral administration include the incorporation of drugs in liposomes, whereas the system favoured for respiratory delivery is the nasal route. The improved oral delivery of polypeptides remains an elusive goal.     

Transdermal drug delivery

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.