Biodegradable polymeric nanoparticles as drug delivery devices

Biodegradable nanoparticles for drug and gene delivery to cells and tissue

Shape memory polymer compositions, articles of manufacture thereof, and methods of preparation and use thereof are described. The shape memory polymer compositions can hold more than one shape in memory. Suitable compositions include at least one hard segment and at least one soft segment. The Ttrans of the hard segment is preferably between -30 and 270 °C. At least one of the hard or soft segments can contain a cross-linkable group, and the segments can be linked by formation of an interpenetrating network or a semi-interpenetrating network, or by physical interactions of the blocks. Objects can be formed into a given shape at a temperature above the Ttrans of the hard segment, and cooled to a temperature below the Ttrans of the soft segment. If the object is subsequently formed into a second shape, the object can return to its original shape by heating the object above the Ttrans of the soft segment and below the Ttrans of the hard segment. The compositions can also include two soft segments which are linked via functional groups which are cleaved in response to application of light, electric field, magnetic field or ultrasound. The cleavage of these groups causes the object to return to its original shape.

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Shape memory polymers

Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the site of action, and at present several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles ("first-generation liposomes") to "second-generation liposomes", in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend blood-circulation time while reducing mononuclear phagocyte system uptake (stealth liposomes). This technology has resulted in a large number of liposome formulations encapsulating active molecules, with high target efficiency and activity. Further, by synthetic modification of the terminal PEG molecule, stealth liposomes can be actively targeted with monoclonal antibodies or ligands. This review focuses on stealth technology and summarizes pre-clinical and clinical data relating to the principal liposome formulations; it also discusses emerging trends of this promising technology.

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Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential.

23 Stereocontrol of Lactide ROP 6164 231 Isotactic Polylactides 6164 232 Syndiotactic Polylactides 6166 233 Heterotactic Polylactides 6166 3 Anionic Polymerization 6166 4 Nucleophilic Polymerization 6168 41 Mechanistic Considerations 6168 42 Catalysts 6169 421 Enzymes 6169 422 Organocatalysts 6169 43 Stereocontrol of Lactide ROP 6170 44 Depolymerization 6170 5 Cationic Polymerization 6170 6 Conclusion and Perspectives 6171 7 Acknowledgments 6173 8 References and Notes 6173

Controlled ring-opening polymerization of lactide and glycolide.

Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake?

Introduction: Orodispersible films for oral delivery are gaining popularity. Whereas breath-fresheners and over-the-counter products have already become quite common in the US, the first prescription drug films were introduced into the EU and US markets only very recently. Already considered as a unique Rx (prescription drug) dosage form by the FDA (oral soluble film), such products are not substitutable by conventional oral dosage forms. The official term defined by the European Medicines Agency is orodispersible film (ODF). Areas covered: This review gives an overview on the benefits of ODFs, typical excipients and products already available on the market. ODFs are defined and differentiated from other films and dosage forms. Possible manufacturing methods are described. As ODFs are not yet listed in one of the pharmacopoeias, possible methods for characterization and quality control are discussed. Required characteristics, advantages and disadvantages are elaborated. Biopharmaceutical considerations ar...

Advances in orodispersible films for drug delivery.

Purpose. Aim of the study was the evaluation of the potential of novel tetanus toxoid (TT) loaded nanoparticles (NP) for electing an immune response in mice against TT. 
Methods. Six week-old female Balb/c mice were immunized by oral (p.o.), nasal (i.n.) and intraperitoneal (i.p.) application of TT NP loaded by adsorption. As polymer a novel polyester, sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide), SB(43)-PVAL-g-PLGA was used. Blood samples were collected 4 and 6 weeks after immunization and assayed for serum IgG- as well as IgA antibody titers by ELISA. NP formulations varying in size and loading were compared to alum adsorbates as well as to TT solutions. 
Results. Both, p.o. and i.n. administration of TT associated NP increased serum titers up to 3 × 103 (IgG) and 2 × 103 (IgA). While small NP induced significantly higher titers then larger ones after oral administration, intermediate NP induced antibodies after nasal application. Of the mucosal routes investigated, i.n. seems to be more promising compared to p.o. immunization. 
Conclusions. Antigen loaded NP prepared from surface modified polyesters combined with CT show considerable potential as a vaccine delivery system for mucosal immunization. The results warrant further experiments to explore in more detail the potential use of NP as mucosal vaccine delivery system.

Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice.

Sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide)s facilitate the preparation of small negatively charged biodegradable nanospheres.

Biodegradable comb polyesters: Part 1 synthesis, characterization and structural analysis of poly(lactide) and poly(lactide-coglycolide) grafted onto water-soluble poly(vinyl alcohol) as backbone

Armin Breitenbach

Papers

Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake?

Advances in orodispersible films for drug delivery.

Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice.

Sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide)s facilitate the preparation of small negatively charged biodegradable nanospheres.

Biodegradable comb polyesters: Part 1 synthesis, characterization and structural analysis of poly(lactide) and poly(lactide-coglycolide) grafted onto water-soluble poly(vinyl alcohol) as backbone