Natural endogenous materials (NEMs), such as cell and cell derivatives, polysaccharide, protein and peptide, and nucleic acid-derived vectors, often exhibit biocompatibility, biodegradability and natural homing ability, which can minimize adverse reactions in vivo and have the potential to improve drug delivery efficacy. Currently, a variety of drug delivery systems (DDSs) based on NEMs have been constructed for macromolecules to address the challenges posed by their inherent large size, intricate structure, low permeability, and susceptibility to harsh environments. The aim of this article is to provide a comprehensive overview of various delivery strategies that predominantly utilize NEMs as carriers for macromolecular delivery. By thoroughly discussing the pros and cons of NEM-based DDSs, we hope to provide valuable insights into future innovations in pharmaceutical science, with a focus on improving therapeutic outcomes through advanced drug formulations.
Animals ; Humans ; Biological Products/chemistry* ; Drug Carriers/chemistry* ; Drug Delivery Systems ; Macromolecular Substances/chemistry*

The oral administration of bioactive macromolecular drugs such as proteins, peptides and nucleic acids represents unprecedented challenges from the drug delivery point of view. One key consideration is how to overcome the gastrointestinal tract absorption barrier. Recent studies suggest that microfold cell (M cell), a kind of specialized antigen-sampling epithelial cell which is characterized by a high endocytic rate and low degradation ability, may play an important role in macromolecule oral absorption. The development of an in vitro M cell coculture system and its modified models greatly advanced the study of M cells and the development of oral delivery system for macromolecular drugs. The special structure, function and formation characteristics, and biomarkers of M cell are summarized in this review. The applications of in vitro M cell models in developing oral delivery system ofbioactive macromolecular drugs are discussed.
Administration, Oral ; Animals ; Drug Delivery Systems ; methods ; Humans ; Intestinal Mucosa ; cytology ; Macromolecular Substances ; administration & dosage ; pharmacokinetics ; Models, Biological ; Peptides ; administration & dosage ; pharmacokinetics ; Peyer's Patches ; cytology ; Proteins ; administration & dosage ; pharmacokinetics ; Vaccines ; pharmacokinetics

Dendrimers are highly branched macromolecules that have attractive nano-sized architectures. It seems that they can enter various cells easily because of their unique nanostructures and chemical properties, which make them to be one of important candidates of non-virus carriers for drug delivery or gene therapy. However, the understanding of cytotoxicity and related mechanisms of dendrimers are still limited. In recent years there has been rapid increases of researches regarding the biological effects of dendrimers, including the interactions of dendrimers to cells, transport mechanisms, intracellular distribution and biodistribution in vivo, as well as improvement of biocompatibility of dendrimers by surface engineering. In this paper, recent advances in the investigations of biological effect and surface modification for the dendrimers as drug or gene delivery systems were reviewed.
Animals ; Dendrimers ; chemistry ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Humans ; Macromolecular Substances ; chemistry ; Nanostructures

In an earlier study, a site directed mutant rFVIII (rFVIII(m), Arg(336) -> Gln(336)) expressed in baculovirus-insect cell (Sf9) system was found to sustain high level activity during incubation at 37 for 24 h while the cofactor activity of normal plasma was declined steadily. In this study, a mutant B-domain deleted rFVIII(m), Arg(336) -> Gln(336) expressed in baculovirus-insect cell (Sf9) system was characterized for its enzymatic and chemical properties. The expressed rFVIII(m) and plasma FVIII (pFVIII) were purified by immunoaffinity column chromatography and identified by Western blot analysis. The partially purified rFVIII(m) exhibited cofactor specific activity of 2.01 X 10(3)units/mg protein. The molecular weight of rFVIII(m) ranged between 40 to 150 kDa with a major band at 150 kDa. Treatment of both rFVIII(m) and pFVIII with thrombin increased their cofactor activity in a similar pattern. Treatment of both the activated rFVIII(m) and native FVIII with APC decreased their cofactor activities, however, the former exhibited a slower decrease than the latter, although no significant difference was present. rFVIII(m) formed a complex with vWF, resulting in a stabilized form, and the lag period of thrombin-mediated activating was extended by vWF association. These results implicated that rFVIII(m) expressed in baculovirus-insect cell system had a comparable capacity as FVIII cofactor activity and might be a good candidate for the FVIII replacement therapy for hemophilia A patients.
Animals ; Baculoviridae/genetics ; Cell Line ; Factor VIII/biosynthesis/*genetics/isolation & purification/*metabolism ; Insects ; Macromolecular Systems ; Mutation/*genetics ; Protein C/pharmacology ; Recombinant Proteins/biosynthesis/*genetics/isolation & purification/*metabolism ; Thrombin/pharmacology ; von Willebrand Factor/metabolism

The measurement and analysis of sedimentation equilibrium provides one of the most powerful and widely applicable methods for the characterization of reversible associations of macromolecules in solution. Recent developments in instrumentation, experimental design, and data analysis have substantially broadened the range of systems to which this technique may be applied, simplified its application, and reduced the cost of acquiring analytical capability.
Animal ; Human ; Kinetics ; Macromolecular Systems* ; Molecular Weight ; Proteins/chemistry ; Proteins/analysis ; Solutions ; Ultracentrifugation/methods ; Ultracentrifugation/instrumentation*