Biodegradable Microspheres Based on Gelatin-Porcine Mucin Admixtures: in Vitro and in Vivo Delivery Studies

Abstract

Microspheres are one of the multiparticulate delivery systems which are formulated to obtain prolonged or controlled drug delivery, to improve bioavailability or stability and to target drugs to specific sites. [2][3][4][5][6][7][8][9] In the pharmaceutical arena, microspheres have been shown to protect sensitive macromolecules from enzymatic and acid degradation and can offer additional advantages such as limiting fluctuation within therapeutic range, reducing side effects, decreasing dosing frequency and improving patient compliance. [10][11][12][13][14][15] Until recently, mucus had been assumed as an inert blanket, serving as a mechanical barrier against potentially injurious chemicals, bacteria and enzymes.16) It has become clear in recent years, however, that mucus glycoproteins or mucins are capable of interacting in various ways with many biologically important entities such as enzymes, polymers, cations, drugs, viruses, cells surfaces and bacteria.17,18) Encapsulation of drugs into mucoadhesive microspheres has been reported to lead to a controlled release of drugs including protein and peptide drugs 19) in addition to other desirable advantages of delivering macromolecules via microspheres. According to origin and pre-treatment of the utilized collagen, two major types of gelatin are commercially produced. Type A gelatin, also known as basic gelatin, is obtained from porcine skin with acidic pre-treatment prior to the extraction process and is known to have an isoelectric point (IEP) of 9.0. The second prevalent gelatin species (type B), also known as acidic gelatin, is extracted from ossein and cut hide split from bovine origin following an alkaline pre-treatment (liming). During this extraction process, the amide groups of asparagines and glutamine are hydrolyzed into carboxyl groups, thus converting many of the residues to aspartate and glutamate. 20,21) Consequently, the electrostatic nature is affected and in contrast to type A which has an IEP of 9.0, the higher number of carboxyl groups per molecule reduces the IEP of type B gelatin to between 4.8 and 5.2.Although the rectal route should certainly not be the route of first choice, it can in certain circumstances be of immense benefit to the patient. In spite of its few limitations, the rectal route is still used in many different therapies, intended either for local or for systemic effect. For the attainment of a systemic effect, all orally given drugs including antibiotics, hormones, antihistamines, tranquilizers, analgesics and anti-inflammatory agents can be administered by the rectal route. 22)Systemic treatment by the rectal route is of particular value for treating infants, administering drugs such as aminophylline that cause gastric irritation and for treating patients who are unconscious, mentally disturbed or unable to tolerate oral medication because of vomiting or pathological conditions of the alimentary canal. The above background prompted us to explore the rectal route, for the delivery of cefaclor, a broad spectrum, second generat...

Interactions of salivary mucins and saliva with food proteins: a review

“…The water sorption behavior in the two media further confirmed a modification of the gelatin microspheres by the mucin (Ofokansi et al, 2007). A possible enhancement of the mucoadhesive properties of gelatin microspheres by the soluble portion of porcine mucin due to the modified intermolecular network and possibly other characteristics of gelatin in the presence of mucin was suggested in another study by Ofokansi et al (2009).…”

Hybrid Mucin‐Vaterite Microspheres for Delivery of Proteolytic Enzyme Chymotrypsin

“…[ 11 ] Biocompatibility and biodegradability of natural mucins further premise their use in fabrication of drug carriers. [ 11,12 ] Generally, the hybrids of mucin with other biopolymers are employed, e.g., polyethylene glycol, [ 13,14 ] gelatin, [ 15 ] alginate, [ 16 ] cellulose, [ 17 ] methylcellulose, [ 18 ] chitosan. [ 19 ]…”

“…[11] Biocompatibility and biodegradability of natural mucins further premise their use in fabrication of drug carriers. [11,12] Generally, the hybrids of mucin with other biopolymers are employed, e.g., polyethylene glycol, [13,14] gelatin, [15] alginate, [16] cellulose, [17] methylcellulose, [18] chitosan. [19] From the other side, the delivery of proteins requires the compliance with some additional prerequisites such as their protection from the degradation and preservation of their biological activity, which strictly depends on labile protein structure.…”

Medicinal and Pharmaceutical Applications of Mucin and its Derivatives

“…Hence, the detection of these enzymes may be indicative of the presence of invading organisms and may be used as a diagnostic tool. Mucins may play a key role in the pharmaceutical industry as a drug delivery agent if properly harnessed [8][9][10][11][12][13].…”