- Perspective For Advancements
Polymeric drug carriers Polymers are the most versatile class
of materials and are widely used in pharmaceutical ,medical ,biomedical
engineering, food and cosmetic industry. When a polymer is judiciously
combined with a drug or other active agents in such a way that this
active agent is released from the drug in a pre designed manner,
a controlled drug delivery system is obtained.
major advantages that polymeric drug carriers offer can be listed
· Decrease in dosage
frequency and increased patient compliance
· Localized drug delivery
· Reduced toxicity
· Increased drug absorption
· Protection of drug in physiological environment
The polymeric drug
carriers can be broadly classified into natural and synthetic
drug carriers based on their origin. is a disease of antiquity and
civilization. It still remains one of the top three fatal infectious
diseases, together with AIDS and malaria. Despite medical progress
in fighting tuberculosis, the disease remains a major health problem,
especially in developing countries that are being ravaged by the
The World Health
Organization (WHO) has identified tuberculosis as one of the
most important emerging global health threats, with an estimated
one-third of the world population infected with the causative agent.
Despite the existence of effective treatment, the disease burden
remains high due to logistic and operational problems, including
those related to access to TB services. Roughly 80 percent of all
active tuberculosis cases are found in Asia and sub-Saharan Africa.
Southern Africa has the highest rate in Africa of people suffering
from both TB and HIV, with more than 9 million people infected.
Of the 13 million tuberculosis patients who are also HIV-positive
on the continent, about 9,5 million of them are believed to be in
southern Africa, which calls for greater efforts to expand the control
WHO states that
at least 8 million people acquire tuberculosis while two million
deaths as a result of the disease are recorded every year worldwide.
Virtually wiped out in the so-called developed world, tuberculosis
has for sometime been regarded as a largely Third World disease.
Chemotherapy of tuberculosis As mankind has been afflicted by tuberculosis
from pre-historic times, a plethora of treatments, ranging from
traditional healing to surgery has been described, however, it was
not until 1943,when Selman Waksman discovered streptomycin, that
physicians had at their disposal as a powerful antituberculosis
agent with scientifically proven activity. Shortly afterwards, in
1946, para-aminosalicylic acid was shown by Jorgan Lehmann to be
active against M.tuberculosis and in 1952, three pharmaceutical
companies simultaneously announced the discovery of highly effective
antitubercular drug, isoniazid (INH). In the early days of tuberculosis
chemotherapy, these drugs were used individually and in many cases,
despite good initial response, the patients developed drug resistance.
Consequently, regimens were developed in which streptomycin was
associated with another drug. The duration of treatment lasted from
culminated in the first generation of multidrug treatment
regimens for tuberculosis. These were subsequently improved
and strengthened as new drugs, such as ethambutol and rifampicin
were introduced in1962 and 1967 respectively. Pyrazinamide
compound, which is bactericidal at acidic pH and acts on intracellular
bacteria, was found to be of great value.
chemotherapy of tuberculosis As a result of much research
and many controlled clinical trials, the current regimens
for short course chemotherapy were evolved (WHO, 1983).
lasts for 6-8 months and consists of two phases(Table 2) i.e.Intensive
phase which lasts for 2 months aimed at sputum negativization
and prevention of selection of resistant strains and continuous
phase aimed at sterilization and relapse free resolution.These
short course treatment regimens are able to cure multibacillary
forms of tuberculosis after as little as 6 months of treatment
and have become the standard care throughout the world.
Table 2 Short course
treatment of tuberculosis Phase Duration Drugsadministered Dose
(mg/Kg b.w.) Aim Intensive(Bactericidal) 2 months INHRIFPZAEMB 51015-3015-25
Reduces clinical symptoms, risk of transmission and emergence of
drug resistance Continuous(Sterilizing) 4-6 monthsDrugs employed
in tuberculosis chemotherapy
Numerous antibiotics with antituberculous activity are available,
including natural products such as aminoglycosides and cycloserine;synthetic
compounds such as nicotinamide analogues and semisynthetic compounds
such as rifamycins. These have been classified as:
These combine the greatest level of efficacy with an acceptable
degree of toxicity; these include isoniazid, rifampicin, pyrazinamide,
ethambutol and streptomycin.
-As drug resistance is very frequent in tuberculosis, it may
be necessary to resort to al;ternative drugs including ofloxacin,
ciprofloxacin, ethionamide, para-aminosalicylic acid, cycloserine,
amikacin, kanamycin and capreomycin.
For TB treatment
to be successful a number of requirements are to be met:
· Antibiotics must be given for a long period of 6-8 months to prevent
relapse after treatment is stopped
· Antibiotics must be given in combination to prevent selection
of mutant strains
· Clinician and patient compliance must be ensured.
` When administered appropriately, combination therapy can be highly
effective owing to:
· Regimens employing firstline agents are orally bioavailable
· The therapy is relatively cheap
· Cure rates exceeding 85% are possible
Drawbacks of chemotherapy
In spite of having an immense chemotherapeutic efficacy the conventional
chemotherapy of tuberculosis is associated with certain inherent
drawbacks: Patient non-compliance-The
current regimens of antiTB therapy are complex and lengthy. Adherence
to 6-8 month chemotherapy with a combination of drugs is often difficult.
Moreover, treatment programmes require substantial supervision to
monitor intake and tolerability of drugs, which is often difficult
drug intake is often associated with emergence and expansion
of multidrug resistant strins thereby further complicating the therapy
of tuberculosis. Drug toxicity-For the most part, TB chemotherapy
is well tolerated. However, the potential for drug toxicity has
been highlighted by several reports on the rates of adverse reactions
during routine curative treatment (Chaisson et al, 2003) and by
unanticipated hepatotoxicity of antitubercular drugs
drug-drug interactions particularly between the rifamycins and
antiretroviral drugs (antiprotease drugs) may also complicate the
chemotherapy of tuberculosis.
administration of antitubercular drugs in free form causes their
dilution and premature metabolic degradation (Deol et al, 1997).The
drugs that reach the target site is therefore lower than the effective
concentration required, which might result in the primary resistance
are being employed for improving the chemotherapy of tuberculosis
New drug development-
numerous new drugs with diverse antimycobacterial activities
are in the pipeline including flouroquinolones ,oxazolidones ,nitroimidazopyran
Newer drug targets-
Several enzymes being encoded by mycobacterial genes have been
recently reported to play an important role in virulence and persistence
(Mckinney et al, 2000), enzymes involved in polyketide synthesis
like polyketide synthase (George et al, 1999).
Although, the development
of improved antimycobacterial drugs and drug targets is an important
issue to the scientific community the currently used antitubercular
drugs still hold a great chemotherapeutic strength. Since compliace
is a major issue in battle against tuberculosis,improved and efficient
methods for the effective delivery of antiTB drugs should be a key
issue in regard to the therapy aimed at :
· Achieving therapeutically
active levels of antitubercular drugs alongwith reduced dosing regimens
for addressing the issues related to compliance(Barrow,2004).
· Directing the sustained delivery of drugs constantly towards the
INHRIF 510 Reduces the risk of relapse.
Contributing Author: Anjali Sharma, I am a Ph.D.
student of Biochemistry working in PGIMER. I am a national fellowship
holder with a very good academic record and 3 international research