Pharmaceutical Manufacturing Handbook: Production and

424 BIODEGRADABLE POLYMER-BASED MICROSPHERES
The microsphere - adsorbed DNA induced a mixed Th1 – Th2 immune response as
opposed to Th1 immune responses elicited by the naked DNA.
JEV - loaded poly(lactide) (PLA) lamellar and PLG microspheres were successfully
prepared with low - molecular - weight PLA by the precipitate method and with
6% w/v PLG in the organic phase, 10% w/v PVP, and 5% w/v NaCl in the continuous
phase by using a w/o/w emulsion/solvent extraction technique, respectively [233] .
The JEV incorporation, physicochemical characterization data, and animal results
obtained in this study may be relevant in optimizing the vaccine incorporation and
delivery properties of these potential vaccine targeting carriers.
Hepatitis B Virus Hepatitis B is one of the most important infectious diseases in
the world. Approximately 350 million people worldwide are chronic carriers of the
hepatitis B virus (HBV), which accounts for approximately one million deaths annually.
PLGA microspheres loaded with recombinant HBsAg were formulated using
a double - emulsion technique. The pharmaceutical characteristics of size, surface
morphology, protein loading effi ciency, antigen integrity, release of HBsAg - loaded
PLGA microspheres, and degradation of the polymer in vitro were evaluated [234 –
237] . Based on these fi ndings in vitro and in vivo, it was concluded that HBsAg was
successfully loaded into the PLGA microspheres, which can autoboost an immune
response, and the HBsAg - loaded PLGA microsphere is a promising candidate for
the controlled delivery of a vaccine.
5.2.6.2 Proteins
Prolidase Defi ciency of this enzyme results in chronic intractable ulcerations of
the skin, particularly of lower limbs, since it is involved in the fi nal stages of protein
catabolism. To counteract the problem, the enzyme was encapsulated in PLGA
microspheres by a double - or multiple - emulsion technique, in vitro and ex vivo
evaluations were done, and the results indicated that microencapsulation stabilizes
the enzymatic activity inside the PLGA microspheres resulting in both in vitro and
ex vivo active enzyme release, hence opening the doors for the possibility of enzyme
replacement therapy through microencapsulation [238] . Further evaluation from
the same research group for prolidase - loaded PLGA microspheres is reported
elsewhere [239, 240] .
Insulin Insulin is the most important regulatory hormone in the control of glucose
homeostasis. The World Health Organization (WHO) has indicated that more than
50 million people around the world suffer from diabetes and require daily parenteral
injections of insulin to stay healthy and live normally. For the treatment of type
I diabetes insulin still is number one, with three subcutaneous injections to be taken
per day. A controlled - release system for a long - term therapy of this disease is the
need of the hour, as this can obviate the need for painful injection given a number
of times to the diabetes patients. Insulin was encapsulated in blends of poly(ethylene
glycol) with PLA homopolymer and PLGA copolymer by a w/o/w multiple -
emulsion technique with entrapment effi ciencies up to 56 and 48% for PLGA/ PEG
and PLA/ PEG, respectively [12] . Insulin - loaded microspheres were capable of
controlling the release of insulin for 28 days with in vitro delivery rates of 0.94 and
0.65 μ g insulin/mg per particle per day in the fi rst 4 days and steady release with a