US 2018/0055777 Al  1  Mar. 1, 2018  HYDROGEL BEADS WITH  SELF-REGULATING MICROCLIMATE PH  PROPERTIES  CROSS-REFERENCE TO RELATED  APPLICATIONS  STATEMENT REGARDING FEDERALLY  SPONSORED RESEARCH & DEVELOPMENT  FIELD OF THE DISCLOSURE  BACKGROUND  BRIEF SUMMARY  BRIEF DESCRIPTION OF THE DRAWINGS  [0013]  FIG.  1  is a schematic diagram showing the fabri› cation of self-adjusting microclimate pH hydro gel beads; the  [0012]  The patent or application file contains at least one  drawing executed in color. Copies of this patent or patent  application publication with color drawing(s) will be pro› vided by the Office upon request and payment of the  necessary fee.  [0005]  Research has indicated that encapsulation in col› loidal delivery systems can improve the handling, applica› bility, chemical stability, and oral bioavailability of many  bioactive agents. Colloidal delivery systems may be fabri› cated using different procedures and methods based on the  molecular and physicochemical properties of the bioactive  agents. One of the most promising approaches to create  colloidal delivery systems is to fabricate hydrogel beads  with bioactive agents trapped inside. Hydrogel beads nor› mally contain hydrophilic, porous, and elastic polymer  matrices, which can improve the stability ofbioactive agents  during storage and control their release after oral intake.  Because hydrogel beads are formed using mild preparation  conditions with food-grade biopolymers (e.g., polysaccha› rides and protein) that do not usually adversely affect the  properties of encapsulated bioactive agents, they can be  found in the applications of a broad range fields from food  to medicine.  [0011]  In yet another aspect, a method of making an  encapsulated functional agent comprises mixing a gelling  polymer, a functional agent, and a buffering agent having  low water solubility to form a mixture, forming hydrogel  beads from the mixture, and crosslinking at least a portion  of the gelling polymer in the hydro gel beads to provide the  encapsulated functional agent, wherein at least a portion of  the buffering agent is in solid form in the hydrogel bead.  [0010]  In another aspect, also included are pharmaceutical  and food compositions comprising the hydrogel beads.  [0009]  In one aspect, a composition comprises a hydrogel  bead in an external matrix, the hydrogel bead comprising an  at least partially crosslinked gelling polymer, the hydrogel  bead having encapsulated therein a functional agent, and a  buffering agent having low water solubility, wherein at least  a portion of the buffering agent is in solid form in the  hydrogel bead.  [0004]  There is considerable interest in the development  of colloidal delivery systems to encapsulate, protect and  deliver bioactive agents (nutrients, micronutrients, nutraceu› ticals, and drugs) in the food, supplement, and pharmaceu› tical industries. Numerous types of bioactive agents can be  encapsulated and delivered such as proteins, peptides, amino  acids, probiotics, prebiotics, vitamins, minerals, nutraceuti› cals, triacylglycerol oils, flavors, colors, antimicrobials, pre› servatives, and the like. For example, bioactive proteins are  often encapsulated due to their sensitivity to chemical deg› radation and their potential for causing off-flavors (such as  bitterness or astringency). Probiotic bacteria can be pro› tected from acidic stomach conditions as they move through  the gastrointestinal tract (GIT) to areas where their benefi› cial actions are most effective (such as the colon). Many  lipophilic bioactive agents (e.g., curcumin and carotenoids)  are encapsulated to address the limitations of their incorpo› ration into food products such as low water-solubility, poor  chemical instability, and low bioaccessibility. Many natural  colors and flavors are encapsulated to inhibit their chemical  degradation under unfavorable environmental conditions.  [0008]  What is needed are new strategies for providing  hydrogel beads that can improve the stability of encapsu› lated bioactive agents.  [0007]  Research has been carried out to improve the  pH-stability of substances encapsulated in hydrogel beads,  e.g., by coating the beads with one or more layers of  biopolymers using electrostatic deposition, or by crosslink› ing the hydrogel matrix using specific enzymes. These  approaches are based on delaying the diffusion of pH  determining ions into the hydrogel beads. However, these  approaches have been shown to have a limited protective  effect and also have other limitations, i.e., the fabrication  procedure is complex and the encapsulated bioactive agents  are not released at the desired site of action.  [0003]  The present disclosure is related to hydrogel beads,  specifically hydrogel beads for delivery ofbioactive agents.  [0002]  This invention was made with govermnent support  under 2014-67017-21635 and 2016-31100-06025 awarded  by the USDA, National Institute of Food and Agriculture  (NIFA). The government has certain rights in the invention.  [0001]  This application claims priority to U.S. Provisional  Application Ser. No. 62/381,748 filed on Aug. 31, 2016, and  U.S. Provisional Application Ser. No. 62/402,017 filed on  Sep. 30, 2016, which are incorporated herein by reference in  their entirety.  [0006]  Many bioactive agents are highly susceptible to  physical, chemical or biological degradation under one set  of pH conditions, but are relatively stable under another set  of pH conditions. For example, some natural colors rapidly  fade under highly acidic pH conditions, but slowly under  neutral conditions. Many probiotics (bacteria beneficial to  gut health) are rapidly inactivated under highly acidic con› ditions, but remain viable under neutral conditions. A major  drawback associated with the use of conventional hydrogel  beads for the encapsulation of these pH-labile bioactive  agents is that they are highly porous, and so acid or alkaline  determining ions (such as H+ or OH-) can easily diffuse in  or out of them, thereby causing the pH inside the beads to  be fairly similar to that outside. As a result, any pH-labile  bioactive agents may be readily degraded when they are  encapsulated in this type of bead. The pH sensitivity of  conventional hydrogel beads therefore hinders their wide› spread applications in the food, supplement, and pharma› ceutical industries for encapsulating pH-labile bioactive  agents. 