268
L-DOPA [(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic
acid] is the gold standard for the treatment of Parkinson’s disease
(PD), which afflicts approximately 0.3% of the entire population,
causing symptoms such as tremors, rigidity, bradykinesia, and akinesia. L-DOPA acts as a prodrug that is absorbed in the small
intestine and carried to the brain by the bloodstream. Since the
plasmatic concentration of L-DOPA tends to fluctuate over time,
drug delivery systems capable of releasing L-DOPA with stable and
prolonged kinetics are necessary to prevent on-off effects and thus
to improve the patients’ quality of life. L-DOPA-imprinted polycarbonate β-CD-based NSs were obtained by cross-linking β-CD
with CDI in the presence of highly reactive and unstable L-DOPA
molecules [85]. The stereochemistry of the β-CD/L-DOPA complex was analyzed by the ROESY experiment (Fig. 6). The recorded
data are consistent with the inclusion of the aromatic moiety of
L-DOPA in the lipophilic cavity of the β-CD; hence the protective
action of β-CD on L-DOPA during the synthesis reactions through
the formation of inclusion complexes can be hypothesized. Finally,
in vitro release experiments were performed. L-DOPA was released
in its active form by the molecularly imprinted NSs with prolonged
and controlled kinetics over the first 48 h [85].
Telmisartan (TEL) belongs to BCS class II drugs. It is an antihypertensive medication which belongs to angiotensin II receptor
(AT1) antagonists. Therapy with this drug offers a good quality of
life for hypertensive patients; however its dissolution rate limits its
bioavailability. The aqueous solubility of TEL is estimated to be
9.9 μg/mL at neutral pH. To enhance the solubility and solve bioavailability problems of TEL, it was incorporated by solvent evaporation method into β-CD carbonate NSs. Phase solubility studies
were carried out, and β-CD complex of TEL was compared with
plain TEL and NS complexes of TEL. It was found that the solubility of TEL was increased by 8.53-fold in distilled water, 3.35fold in 0.1 N HCl, and 4.66-fold in phosphate buffer pH 6.8 by
incorporating NaHCO 3 in drug–NS complex than TEL alone.
NaHCO 3 (ternary component alkalizer) in the NS-based complex
synergistically enhanced the dissolution of TEL by modulating
microenvironmental pH and by promoting the amorphization of
the drug [86].
Nifedipine acts as an oral calcium channel-blocking agent
employed in the treatment of hypertension and angina pectoris.
Although the oral route for nifedipine is extensively accepted, it is
coupled with contraindicative manifestations such as gastrointestinal (GI) disturbance, first-pass metabolism, and less oral bioavailability because of its short biological half-life with significant
fluctuations in plasma concentrations and possible photodegradation [87].
2.10 Cyclodextrin
Nanosponges
for Hypertension
Medication
Maria Tannous et al.
L-DOPA [(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic
acid] is the gold standard for the treatment of Parkinson’s disease
(PD), which afflicts approximately 0.3% of the entire population,
causing symptoms such as tremors, rigidity, bradykinesia, and akinesia. L-DOPA acts as a prodrug that is absorbed in the small
intestine and carried to the brain by the bloodstream. Since the
plasmatic concentration of L-DOPA tends to fluctuate over time,
drug delivery systems capable of releasing L-DOPA with stable and
prolonged kinetics are necessary to prevent on-off effects and thus
to improve the patients’ quality of life. L-DOPA-imprinted polycarbonate β-CD-based NSs were obtained by cross-linking β-CD
with CDI in the presence of highly reactive and unstable L-DOPA
molecules [85]. The stereochemistry of the β-CD/L-DOPA complex was analyzed by the ROESY experiment (Fig. 6). The recorded
data are consistent with the inclusion of the aromatic moiety of
L-DOPA in the lipophilic cavity of the β-CD; hence the protective
action of β-CD on L-DOPA during the synthesis reactions through
the formation of inclusion complexes can be hypothesized. Finally,
in vitro release experiments were performed. L-DOPA was released
in its active form by the molecularly imprinted NSs with prolonged
and controlled kinetics over the first 48 h [85].
Telmisartan (TEL) belongs to BCS class II drugs. It is an antihypertensive medication which belongs to angiotensin II receptor
(AT1) antagonists. Therapy with this drug offers a good quality of
life for hypertensive patients; however its dissolution rate limits its
bioavailability. The aqueous solubility of TEL is estimated to be
9.9 μg/mL at neutral pH. To enhance the solubility and solve bioavailability problems of TEL, it was incorporated by solvent evaporation method into β-CD carbonate NSs. Phase solubility studies
were carried out, and β-CD complex of TEL was compared with
plain TEL and NS complexes of TEL. It was found that the solubility of TEL was increased by 8.53-fold in distilled water, 3.35fold in 0.1 N HCl, and 4.66-fold in phosphate buffer pH 6.8 by
incorporating NaHCO 3 in drug–NS complex than TEL alone.
NaHCO 3 (ternary component alkalizer) in the NS-based complex
synergistically enhanced the dissolution of TEL by modulating
microenvironmental pH and by promoting the amorphization of
the drug [86].
Nifedipine acts as an oral calcium channel-blocking agent
employed in the treatment of hypertension and angina pectoris.
Although the oral route for nifedipine is extensively accepted, it is
coupled with contraindicative manifestations such as gastrointestinal (GI) disturbance, first-pass metabolism, and less oral bioavailability because of its short biological half-life with significant
fluctuations in plasma concentrations and possible photodegradation [87].
2.10 Cyclodextrin
Nanosponges
for Hypertension
Medication
Maria Tannous et al.