Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.

http://science.sciencemag.org/content/sci/249/4976/1527.full.pdf

New methods of drug delivery.

The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices.

Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

Medical devices and applications of polyhydroxyalkanoate polymers

Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives.

This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55–95 µm and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37°C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37°C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.

Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres

The aim of this work was to develop injectable microcapsules containing leuprolide acetate, that would deliver that drug at a zero-order rate over a period of about one month. A large amount of leuprolide acetate, a hydrophilic drug, was entrapped into polylactic aicd (PLA) and copoly-(lactic/glycolic) acid (PLGA) microcapsules prepared by an in-water dring method using a (w/o)/w emulsion. The basic techniques were designed to increase the viwcosities of the inner water phase and w/o emulsion. Under the conditions used, it was possible for the drug to be completely entrapped by the microcapsules in the range of 10 to 20% on the basis of the polymer. However, the release profiles of the drug in vitro were inadequate for controlled release for one month.

A New Technique to Efficiently Entrap Leuprolide Acetate into Microcapsules of Polylactic Acid or Copoly(Lactic/Glycolic) Acid

Polylactic acid (PLA) or copoly(lactic/glycolic) acid (PLGA) microcapsules containing leuprolide acetate were prepared by an in-water drying process and the release patterns were examined in vitro. The release rates were extremely small from microcapsules prepared with PLA of average molecular weight 22500, and from microcapsules prepared with PLGA having average molecular weight 21200 and a copolymer ratio of 75/25 (molar ratio of lactic acid to glycolic acid). The release rate of leuprolide acetate from the microcapsules prepared with PLA of average molecular weight 6000 was relatively fast, but was still too slow to give the desired drug level over one month. Several water-soluble compounds were incorporated into microcapsules prepared with PLA of average molecular weight 22500, in an attempt to increase the release rate by the creation of aqueous channels. These compounds only induced a high initial release and failed to increase drug release. The release profile of the drug from microcapsules prepared with PLGA of average molecular weight 14000 and a copolymer ratio of 75/25 was ideal for one month's release. A small initial release was observed followed by a steady release which lasted for 35d, and approximately followed zero-order kinetics.

Controlled-Release of Leuprolide Acetate from Polylactic Acid or Copoly(Lactic/Glycolic) Acid Microcapsules : Influence of Molecular Weight and Copolymer Ratio of Polymer

The present invention provides a biodegradable high molecular polymer characterized in that the content of water-soluble low molecular compounds, as calculated on the assumption that said compounds each is a monobasic acid, is less than 0.01 mole per 100 grams of said high molecular polymer. The thus-obtained molecular polymer has good aging stability and can be used advantageously as an excipient for pharmaceutical preparations.

Polymer, production and use thereof

Vagal Afferent Fibers and Peripheral 5-HT3 Receptors Mediate Cisplatin-Induced Emesis in Dogs

Microcapsules are advantageously produced with high take-up of a water-soluble drug by preparing a W/O emulsion composed of a water-soluble drug-containing solution as the inner aqueous phase and a polymer-containing solution as the oil phase, dispersing said emulsion in an aqueous phase and subjecting the resulting W/O/W emulsion to an in-water drying, wherein the viscosity of the W/O emulsion used in preparing the W/O/W emulsion is adjusted to about 150 to about 10,000 centipoises.

Masaki Yamamoto

Papers

A New Technique to Efficiently Entrap Leuprolide Acetate into Microcapsules of Polylactic Acid or Copoly(Lactic/Glycolic) Acid

Controlled-Release of Leuprolide Acetate from Polylactic Acid or Copoly(Lactic/Glycolic) Acid Microcapsules : Influence of Molecular Weight and Copolymer Ratio of Polymer

Polymer, production and use thereof

Vagal Afferent Fibers and Peripheral 5-HT3 Receptors Mediate Cisplatin-Induced Emesis in Dogs

Sustained release microcapsule