Bioadhesive Microspheres: A review

Dr. J.K. Patel

Bioadhesion is a
topic of current interest in the design of controlled or targeted drug delivery
systems.

Recent advances of in polymer science and drug carrier technologies
have promulgated the development of novel drug carriers such as bioadhesive
microspheres that have boosted the use of bioadhesion in drug delivery.

Bioadhesive microspheres exhibit a prolonged residence time at site of
application or absorption and facilitate an intimate contact with underlying
absorption surface and thus contribute to improved and/or better therapeutic
performance of drugs. In recent years such bioadhesive microspheres have been
developed for oral, buccal, ocular, rectal, nasal and vaginal routes for either
systemic or local effects. This article presents introduction and the advanced
pharmaceutical applications of bioadhesive microspheres.

Introduction:

The term “bioadhesion”
describes materials that bind to biological substractes, such as mucosal
members. Adhesion of bioadhesive drug delivery devices to the mucosal tissue
offers the possibility of creating an intimate and prolonged contact at the
site of administration. This prolonged residence time can result in enhanced
absorption and in combination with a controlled release of drug also improved
patient compliance by reducing the frequency of administration. Carrier
technology offers an intelligent approach for drug delivery by coupling the
drug to a carrier particle such as microspheres, nanospheres, liposomes,
nanoparticles, etc., which modulates the release and absorption of the drug.
Microspheres constitute an important part of these particulate drug delivery
systems by virtue of their small size and efficient carrier capacity. However,
the success of these microspheres is limited due to their short residence time
at site of absorption. It would, therefore, be advantageous to have means for
providing an intimate contact of the drug delivery system with the absorbing
membranes. This can be achieved by coupling bioadhesion characteristics to
microspheres and developing bioadhesive microspheres [1-5]. Bioadhesive
microspheres include microparticles and microcapsules (having a core of the
drug) of 1-1000 µm in diameter and consisting either entirely of a
bioadhesive polymer or having an outer coating of it, respectively [6].
Microspheres, in general, have the potential to be used for targeted and
controlled release drug delivery; but coupling of bioadhesive properties to
microspheres has additional advantages, e.g. efficient absorption and enhanced
bioavailability of the drugs due to a high surface to volume ratio, a much more
intimate contact with the mucus layer, specific targeting of drugs to the
absorption site achieved by anchoring plant lectins, bacterial adhesins and
antibodies, etc. on the surface of the microspheres.

Bioadhesive
microspheres can be tailored to adhere to any mucosal tissue including those
found in eye, nasal cavity, urinary, colon and gastrointestinal tract, thus
offering the possibilities of localized as well as systemic controlled release
of drugs. Bioadhesive microspheres can be prepared using different techniques.
Application of bioadhesive microspheres to the mucosal tissues of ocular
cavity, gastric and colonic epithelium is used for administration of drugs for
localized action. Prolonged release of drugs and a reduction in frequency of
drug administration to the ocular cavity can highly improve the patient
compliance [7]. The latter advantage can also be obtained for the drugs
administered intranasally due to the reduction in mucociliary clearance of
drugs adhering to nasal mucosa. Microspheres prepared with bioadhesive and
bioerodible polymers undergo selective uptake by the M cells of Peyer patches
in gastrointestinal (GI) mucosa. This uptake mechanism has been used for the
delivery of protein and peptide drugs, antigens for vaccination and plasmid DNA
for gene therapy. Moreover, by keeping the drugs in close proximity to their
absorption window in the GI mucosa, the bioadhesive microspheres improve the
absorption and oral bioavailability of drugs like furosemide and riboflavin [7].

Preparation of
bioadhesive microspheres

Bioadhesive
microspheres can be prepared using any of the following techniques.

Solvent
evaporation, Hot melt microencapsulation, Solvent removal, Hydrogel
microspheres, Spray drying, Phase inversion Microencapsulation.

Characterization
of Bioadhesive Microspheres

Bioadhesive
microspheres can be characterized by following methods.

Morphological
examination, Production yield, Drug content and loading efficiency, Particle size
measurement, Determination of bulk density, Angle of repose, Zeta potential
study, Swelling property, Infrared absorption study, DSC study, In Vitro/In
Vivo bioadhesion study, In Vitro Drug Release study and Drug Permeation study.

Pharmaceutical
applications:

Bioadhesive
microspheres have been extensively studied for a number of applications.
Majority of these can be understood by classifying these applications on the
basis of route of administration. All these applications have been summarized in
the Table 1.

Table 1: Pharmaceutical
applications of bioadhesive microspheres

Summary

Due
to the large number of target site of bioadhesive drug delivery systems there
are many formulations that may be explore for drug delivery purpose. Bioadhesive
microspheres offer unique carrier system for many pharmaceuticals and can be
tailored to adhere to any mucosal tissue, including those found in eyes, oral
cavity and throughout the respiratory, urinary and gastrointestinal tract. The
bioadhesive microspheres can be used not only for controlled release but also
for targeted delivery of the drugs to specific sites in body. Recent advances
in medicine have envisaged the development of polymeric drug delivery systems
for protein/peptide drugs and gene therapy. Although significant advances have been
made in the field of bioadhesives, there are still many challenges ahead in
this field. Very importance is the development of universally acceptable
standard evaluation methods and development of newer site directed polymers.
Polymeric science needs to be explored to find newer bioadhesive polymers with
the added attributes of being biodegradable, biocompatible, bioadhesive for
specific cells or mucosa and which could also function as enzyme inhibitors for
the successful delivery of proteins and peptides. A multidisciplinary approach
will therefore be required to overcome these challenges and to employ
bioadhesive microspheres as a cutting edge technology for site targeted
controlled release drug delivery of new as well as existing drugs. The future
direction of bioadhesive microspheres lies in vaccine
formulation that adheres to mucosal surface and result in mucosal immunity.

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About Author

Dr. Jayvadan Patel

Assistant Professor, Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva-382711, Gujarat, India. E-mail-jayvadan04@yahoo.com