When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve oral delivery of NCs to treat gastrointestinal (GI) pathologies or for systemic absoption. However, GI instability of targeting moieties compromises this strategy. We explored whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NCs release and targeting in intestinal conditions. We used nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or non-specific IgG. NCs (~160-nm) were encapsulated in ~180-μm microcapsules with an alginate core, in the absence or presence of a chitosan shell. We found >95% NC encapsulation within microcapsules and <10% NC release from microcapsules in storage. There was minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75–85%), slightly attenuated by chitosan. Encapsulated NCs afforded increased protection against degradation (3–4 fold) and increased cell targeting (8–20 fold) after release vs. non-encapsulated NCs. Mouse oral gavage showed that microencapsulation provided 38–65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and 4-9-fold enhanced intestinal biodistribution vs. non-encapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery.
Oral peptide delivery has been one of the major challenges of pharmaceutical sciences as it could lead to a great improvement of classical therapies, such as insulin, alongside making an important number of new therapies feasible. Successful oral delivery needs to fulfill two key tasks: to protect the macromolecules from degradation in the GI tract and to shuttle them across the intestinal epithelium in a safe and efficient fashion. Over the last decade, there have been numerous approaches based on the chemical modification of peptides and on the use of permeation enhancers, enzyme inhibitors and drug-delivery systems. Among the approaches developed to overcome these restrictions, the design of nanocarriers seems to be a particularly promising approach. This article is an overview on the state of the art of oral-peptide formulation strategies, with special attention to insulin delivery and the use of polymeric nanocarriers as delivery systems.
Molecular imprinting is a promising technology that, although successfully used to recognize small molecules, has had many difficulties in recognizing macromolecules such as peptides and proteins. The current technologies used to achieve the macromolecular imprinting are incompatible with diagnosis and recognition in many life sciences applications such as medical devices, food additives, or drug delivery systems that require biocompatible products. We present here a new, biocompatible technology of protein imprinting by means of calcium alginate-based polymer capsules using ionic gelation and without toxic chemicals other than sodium alginate and calcium chloride. These molecular imprinting capsules are capable of recognizing higher quantities of protein than the existing technologies developed until now, with a simple formulation.
Macromolecularly imprinted polymers have been developed to mimic the non-covalent interactions driving molecular recognition in nature. The creation of an engineered antibody mimic would allow for the development of customizable films for biomolecular sensing. To demonstrate this principle, a cross-linked alginate film has been imprinted with bovine serum albumin (BSA) using aqueous biocompatible gelation methods. The imprinting efficiency of the synthesized films imprinted with BSA was determined and compared to the non-specific uptake of complementary proteins which were not imprinted in the alginate matrix. It was found that the recognition of the BSA using an alginate film was 6.4 mg/g polymer, which compares favorably to previously reported macromolecularly imprinted networks. The absorption of non-imprinted cationic proteins by the alginate matrix demonstrates that overcoming non-specific binding needs to be a focus of future work in order to successfully employ these materials towards biomolecular sensing within a physiological environment.
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