Faculty of Pharmacy/CHARUSAT/RPCP Introduction

INTRODUCTION

Approximately one-third of the world population is infected with Mycobacterium

tuberculosis, resulting in more than eight million new cases and two million deaths annually.

Although potentially curative treatments have been available for almost half a century,

tuberculosis (TB) remains the leading cause of preventable deaths in the world today. Recent

implementation of the World Health Organization’s strategy (directly observed therapy,

short-course) has been problematic, and TB remains a major burden in many developing

countries.

One of the major problems is noncompliance to prescribed regimens, primarily because

treatment of TB involves continuous, frequent multiple drug dosing. Adherence to treatment

and the outcome of therapy could be improved with the introduction of long-duration drug

formulations releasing the antimicrobial agents in a slow and sustained manner, which would

allow reduction in frequency and dosing numbers.

Polymeric nanoparticles may offer a solution to overcome this treatment related problem.

Polymeric nanoparticles are made from biocompatible and biodegradable materials such as

polymers, either natural (e.g., cellulose, gelatin, pullulan, chitosan, alginate, and gliadin) or

synthetic (e.g., polylactide (PLA), poly-(lactide-co-glycolide) (PLGA), polyanhydrides, poly-

ε-caprolactone (PCL), and polyphosphazene) (1, 2). In the body, the drug loaded polymeric

nanoparticles is usually released from the matrix by diffusion, swelling, erosion, or

degradation.

The following are among the important technological advantages of nanoparticles as drug

carriers: high stability (i.e., long shelf life); high carrier capacity (i.e., many drug molecules

can be incorporated in the particle matrix); feasibility of incorporation of both hydrophilic

and hydrophobic substances; and feasibility of variable routes of administration, including

oral administration and inhalation. These carriers can also be designed to enable controlled

(sustained) drug release from the matrix.

It is expected that polymeric nanoparticles enable improvement of drug bioavailability and

reduction of the dosing frequency, and may resolve the problem of non-adherence to

prescribed therapy, which is one of the main obstacles in the control of TB epidemics.

Bhavin Patel 1

Faculty of Pharmacy/CHARUSAT/RPCP Introduction

Encapsulation of drug in polymeric material may offers protection to the drugs in GIT

environment.

Polymeric nanoparticles get absorbed from the GIT tract and enter into the blood streams.

The fate of nanoparticles in the gastrointestinal tract has been investigated in a number of

studies (3-5). In general, the uptake of polymeric nanoparticles occurs by transcytosis via M

cells, intracellular uptake and transport via the epithelial cells lining the intestinal mucosa,

uptake via Peyer’s patches.

Polymeric nanoparticles present into the blood provide sustained release of drug. Polymeric

nanoparticles of the drugs present in the blood are identified as foreign bodies by RES

(reticular endothelial system), which intern leads to their engulfment by macrophage system.

M. tuberculosis, M. bovis, and M. africanum are the causative microorganisms for the

tuberculosis. These causative microorganisms of the tuberculosis reside into the macrophages

and they cannot be killed effectively by conventional therapy of tuberculosis due to poor

intracellular targeting which in turn leads to MDR TB (multidrug resistant tuberculosis) and

XDRTB (extensively drug resistant tuberculosis). It is expected that polymeric nanoparticles

of anti-tubercular drug may naturally target the macrophages and may improve therapeutic

outcomes.

To do this, chitosan was chosen as a suitable polymer for the preparation of polymeric

nanoparticles because of its beneficial properties: i.e. it is non-toxic, biocompatible and

biodegradable (6). It has good mucoadhesive and membrane permeability–enhancing

properties due to its cationic nature. They can transit directly and/or adhere to the mucosa,

which is a prerequisite step before the translocation process of particles. Hence, bioadhesion

plays a key role to deliver drugs across the epithelia, avoiding hepatic first pass metabolism

and enzymatic degradation in the GIT. This hydrophilic polymer can easily cross-link with

glutraldehyde (7-9), NaOH (10-12) , ethylene glycol diglycidyl ether (13) and counter poly

anions like tripolyphosphate (TPP) (14-16) to control the release of drugs.

So, broadly it is hypothesized that polymeric nanoparticles may provide sustained release of

antitubercular agent and hence improve the patient compliance by reducing the dosing

frequency. It is also expected that polymeric nanoparticles naturally target the macrophage

where the phathogens of tuberculosis reside. This may increase the efficacy and effectiveness

of the treatment.

Bhavin Patel 2

Faculty of Pharmacy/CHARUSAT/RPCP Introduction

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Faculty of Pharmacy/CHARUSAT/RPCP Introduction

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