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Systemic administration of therapeutics also results in off-target effects, as only a small fraction of the administered dose crosses the BBB, with the remainder accumulating and affecting peripheral tissues 71,72

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The calculation for pI involves averaging the pKa values associated with the second and third ionizable groups, resulting in a pI of 7.59, expressed as: pI = 1/2 (pKa2 + pKa3)

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